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Publisher: John Wiley and Sons   (Total: 1577 journals)

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Showing 1 - 200 of 1577 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 64, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 46, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 49, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 149, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 6, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 3)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 13, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 26, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 50, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 257, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 5, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 35, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 15, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 10, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 14, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 30, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 50, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 137, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 89, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 27, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 33, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 264, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 126, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 16)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 224)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 213, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 37, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 9, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 48, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 24, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 91, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 47, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 7, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 68, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 151, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 48, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 237, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 51, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 14)
Asia & the Pacific Policy Studies     Open Access   (Followers: 15)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 312, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 4, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 13, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 7, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 13, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 4, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 44, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 27, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 14, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 405, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 4, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 69, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 32, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 3, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 36, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 193, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 19, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 37, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 5, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 226, SJR: 2.083, h-index: 125)

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Journal Cover American Journal of Reproductive Immunology
  [SJR: 1.347]   [H-I: 75]   [3 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1046-7408 - ISSN (Online) 1600-0897
   Published by John Wiley and Sons Homepage  [1577 journals]
  • Reduced CD200 expression is associated with altered Th1/Th2 cytokine
           production in placental trophoblasts from preeclampsia
    • Authors: Jie Xu; Yang Gu, Jingxia Sun, Hui Zhu, David F. Lewis, Yuping Wang
      Abstract: ProblemTo determine if altered trophoblast CD200 and CD200R expressions promote inflammatory cytokine production in preeclamptic placentas.Methods of studyPlacental tissue CD200 and CD200R expressions were determined by immunostaining. Tissue sections from first-, second-, and third-trimester, normal term, and preeclamptic placentas were used. CD200 and CD200R expressions and cytokine production of TNFα, sTNFR1, INFγ, IL-4, IL-6, IL-8, and IL-10 were determined in trophoblasts from normal and preeclamptic placentas and in normal trophoblasts transfected with CD200 siRNA.ResultsCD200, but not CD200R, expression was significantly reduced in trophoblasts from preeclamptic compared to normal placentas. Trophoblast from preeclamptic placentas and trophoblast transfected with CD200 siRNA produced significantly more TNFα, sTNFR1, IL-6, and IL-8, but significantly less IL-10, than trophoblasts from normal control placentas.ConclusionDownregulation of CD200 expression resulted in an imbalance of increased Th1 cytokine and decreased Th2 cytokine production in placental trophoblasts in preeclampsia.
      PubDate: 2017-09-20T06:17:27.892041-05:
      DOI: 10.1111/aji.12763
  • A Single Nucleotide Polymorphism of DNA methyltransferase 3B gene is a
           risk factor for recurrent spontaneous abortion
    • Authors: Anita Barišić; Nina Pereza, Alenka Hodžić, Saša Ostojić, Borut Peterlin
      Abstract: ProblemAberrant DNA methylation has been suggested as a potential cause of recurrent spontaneous abortion (RSA). Considering the growing evidence on the important roles of DNA methylation in gametogenesis and early pregnancy, we investigated the potential association of DNA methyltransferase gene polymorphisms (DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686) with RSA in Slovenian reproductive couples.Method of studyA total of 146 couples with ≥3 consecutive spontaneous abortions and 149 control women and men with ≥2 normal pregnancies were included. Genotyping was performed using PCR-RFLP methods.ResultsWe found a statistically significant higher frequency of the DNMT3B rs1569686 GG genotype (X2=7.37;P = .025) and G allele (X2 = 6.33;P = .012) in RSA women compared with controls. Moreover, the odds for RSA in women were increased under the recessive genetic model (GGvsTG+TT: OR=1.92; 95% CI=1.18-3.09; P = .008).ConclusionDNMT3B rs1569686 gene polymorphism in women might be a genetic marker for the susceptibility to RSA.
      PubDate: 2017-09-20T06:16:46.325868-05:
      DOI: 10.1111/aji.12765
  • Chlamydia trachomatis regulates innate immune barrier integrity and
           mediates cytokine and antimicrobial responses in human uterine ECC-1
           epithelial cells
    • Authors: Lucy Rudo Mukura; Danica K. Hickey, Marta Rodriguez-Garcia, John V. Fahey, Charles R. Wira
      Abstract: ProblemChlamydia trachomatis infection is the most common sexually transmitted bacterial infection worldwide and known to increase the risk for HIV acquisition. Few studies have investigated how infection of epithelial cells compromises barrier integrity and antimicrobial response.Method of studyECC-1 cells, a human uterine epithelial cell line, were treated with live and heat-killed C. trachomatis. Epithelial barrier integrity measured as transepithelial resistance (TER), chemokines antimicrobial levels, and antimicrobial mRNA expression was measured by ELISA and Real-time RT-PCR.ResultsEpithelial barrier integrity was compromised when cells were infected with live, but not with heat-killed, C. trachomatis. IL-8 secretion by ECC-1 cells increased in response to live and heat-killed C. trachomatis, while MCP-1, HBD2 and trappin2/elafin secretion decreased with live C. trachomatis.ConclusionLive C. trachomatis suppresses ECC-1 innate immune responses by compromising the barrier integrity, inhibiting secretion of MCP-1, HBD2, and trappin-2/elafin. Differential responses between live and heat-killed Chlamydia indicate which immune responses are dependent on ECC-1 infection rather than the extracellular presence of Chlamydia.
      PubDate: 2017-09-16T06:30:36.413849-05:
      DOI: 10.1111/aji.12764
  • Successful treatment with intrauterine delivery of dexamethasone for
           repeated implantation failure
    • Authors: Tao Zhang; Chunyu Huang, Yan Du, Ruochun Lian, Meilan Mo, Yong Zeng, Gil Mor
      Abstract: ProblemEffective therapy for endometrial receptivity of patients with repeated embryo implantation failure (RIF) is far undeveloped. Whether intrauterine perfusion of dexamethasone (DXM), local administration of drugs with less systematic side-effects, benefit for embryo implantation by suppressing uterine NK (uNK) cells to improve endometrial receptivity remains unknown.Method of studyWomen with RIF were analyzed for the correlation between the percentage of uNK cells during implantation window and following clinical pregnancy rate to determine the appropriate range of uNK for embryo implantation. Women with RIF and extremely increased uNK cells were treated with transvaginal intrauterine perfusion of DXM. Quantification of uNK cells before and after this treatment was analyzed by immunohistochemistry staining for understanding potential underlying mechanism. Pregnancy outcome was evaluated for the efficiency and safety of this novel therapy.ResultsThe clinical pregnancy rate was decreased if the percentage of uNK cells was higher than the 75th percentile (18.06%), which was considered as the cutoff value for increased uNK cells. All eight patients with increased uNK cells responded to DXM-induced decrease on uNK cells number, and seven got clinical pregnancy. Three delivered with a healthy baby at term without any pregnancy complication and three achieved an ongoing pregnancy, but one suffered from early miscarriage.ConclusionWe report for the first time the beneficial effect of intrauterine perfusion of DXM for patients with RIF characterized by high number of uNK cells. The potential mechanism is downregulation of the proportion of uNK cells, which may improve endometrial receptivity and enhance embryo implantation.
      PubDate: 2017-09-16T06:25:33.819563-05:
      DOI: 10.1111/aji.12766
  • Chronic endometritis: Really so relevant in repeated IVF failure'
    • Authors: Amerigo Vitagliano; Carlo Saccardi, Pietro Salvatore Litta, Marco Noventa
      PubDate: 2017-09-16T06:21:49.253467-05:
      DOI: 10.1111/aji.12758
  • Transcription factor CCAAT/enhancer-binding protein-β upregulates
           microRNA, let-7f-1 in human endocervical cells
    • Authors: Kanchana Ayyar; Kudumula Venkata Rami Reddy
      Abstract: ProblemIn endocervical epithelial cells (End1/E6E7), miRNA let-7f plays an important role in the control of innate immunity. The underlying molecular mechanism for let-7f regulation in these cells remains largely unclear.Methods of studylet-7f was knocked down in End1/E6E7 cells using siRNA, and differential gene expression was analyzed by microarray. Differentially expressed genes were validated by qPCR and Western blot. Expression of let-7f was studied by qPCR after inhibition of C/EBPβ with betulinic acid (BA) and pCMVβ plasmid and after overexpression of C/EBPβ with pCMVβ+ plasmid. ChIP assay was performed to confirm binding of C/EBPβ to let-7f promoter. Levels of Lin28A/B were checked by qPCR after similar treatment.Resultslet-7f knockdown (KD) affects the expression of many transcription factors (eg, C/EBPβ) which are important regulators of immune responses. We observed let-7f-1 promoter to contain 6 C/EBPβ binding sites. KD of C/EBPβ led to decreased let-7f expression while overexpression of C/EBPβ increased its expression. Treatment of End1/E6E7 cells with TLR-3 ligand, poly(I:C) increased binding of C/EBPβ at binding sites 3, 5, and 6. Expression of Lin28A/B also changed upon inhibition and overexpression of C/EBPβ. Its expression is opposite to that of let-7f in End1/E6E7 cells.Conclusionlet-7f-1 is a direct target of transcription factor, C/EBPβ in End1/E6E7 cells.
      PubDate: 2017-09-16T06:21:47.968448-05:
      DOI: 10.1111/aji.12759
  • Comparison of the percentages of CD4+ CD25high FOXP3+,
           CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs, in the umbilical cord blood
           of babies born to mothers with and without preeclampsia
    • Authors: Farha El-Chennawi; Ibrahim Mohamed Rageh, Amira Ibrahim Mansour, Mohammed Ibrahim Darwish, Ashraf Antar Elghzaly, Basma El Sayed Sakr, Khaled Mohsen Elbaz
      Abstract: ProblemLittle is known about how preeclampsia affects regulatory T-cell count and functions in umbilical cord blood of babies born to preeclamptic mothers. Here, we analyze the percentage of CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia.Method of studyThe percentage of umbilical cord blood CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs were analyzed by flow cytometry.ResultsCD4+ CD25high FOXP3+ Treg (%) and CD4+ FOXP3+ Treg (%) were significantly lower, while CD4+ CD25low (%) was significantly higher in umbilical cord blood of babies born to preeclamptic mothers.ConclusionPreeclampsia is associated with immune dysregulation which leads to a deficiency in Treg (CD4+ CD25high FOXP3+) in the umbilical cord blood of babies born to preeclamptic mothers.
      PubDate: 2017-09-16T06:21:24.332641-05:
      DOI: 10.1111/aji.12761
  • Expansion of CD4 phenotype among CD160 receptor-expressing lymphocytes in
           murine pregnancy
    • Authors: Matyas Meggyes; Laszlo Szereday, Pal Jakso, Barbara Bogar, Agnes Bogdan, Jasper Nörenberg, Eva Miko, Aliz Barakonyi
      Abstract: ProblemCD160, a cell surface co-receptor, is capable of up- or downregulating cell proliferation, cytotoxicity or cytokine production on lymphocytes. Our aim was to investigate CD160+ lymphocytes in the periphery and at the maternal-foetal interface during murine pregnancy.Method of studyCD4+, CD8+ and gamma/delta T-cell phenotype, TIM3 co-expression and cytotoxic activity of CD160+ lymphocytes of pregnant BALB/c mice were analysed by flow cytometry.ResultsThe percentage of CD160+ lymphocytes in the decidua was unchanged compared to non-pregnant endometrium; however, the ratio of CD4+ cells within the CD160 population was significantly increased. The co-expression of TIM3 co-inhibitory molecule and cytotoxicity of CD160+ cells were increased in the decidua.ConclusionThe expansion of CD4-expressing CD160+ decidual lymphocytes is a new observation suggesting a potential regulatory role of T-cell function during mouse pregnancy. The altered immunological character of CD160+ lymphocytes could play a role in the maintenance of murine pregnancy.
      PubDate: 2017-09-16T06:21:20.682287-05:
      DOI: 10.1111/aji.12745
  • Undifferentiated connective tissue diseases and adverse pregnancy
           outcomes. An undervalued association'
    • Authors: Arsenio Spinillo; Fausta Beneventi, Roberto Caporali, Veronique Ramoni, Carlomaurizio Montecucco
      Abstract: Undifferentiated connective tissue diseases (UCTDs) are a heterogeneous group of disorders characterized by symptoms and signs suggestive of systemic autoimmune rheumatic disease (ARD), but which do not fulfill all the established criteria for definite diagnosis of a condition. Although a third of UCTDs can progress to a definite ARD within months or years, most UCTDs can remain stable for years with minimal disease activity. The annual incidence of UCTD in the general population ranges from 14 to 140 per 100 000 people. UCTDs are associated with the persistence of several circulating autoantibodies including antinuclear, antiphospholipid or antithyroid antibodies. Immunological evaluation of subjects with UCTDs suggests a proinflammatory state and dysregulation of the Th1/Th2 balance. Autoantibodies have well-known deleterious effects on placentation and have been associated with an increased risk of prematurity, fetal growth restriction (FGR), preeclampsia, and congenital atrioventricular heart block. Although epidemiological and biological data suggest a potential negative impact on reproductive outcomes, the relationship between UCTD and pregnancy outcomes has not been adequately studied. While awaiting definitive data from large studies, obstetricians should be aware that rheumatic disorders in their early, incomplete, or undifferentiated phases can adversely affect pregnancy outcomes, increasing the likelihood of pregnancy loss, FGR, preeclampsia, and prematurity.
      PubDate: 2017-09-16T06:21:15.205263-05:
      DOI: 10.1111/aji.12762
  • The extracellular signal-regulated kinase 1/2 triggers angiogenesis in
           human ectopic endometrial implants by inducing angioblast differentiation
           and proliferation
    • Authors: Sefa Arlier; William Murk, Ozlem Guzeloglu-Kayisli, Nihan Semerci, Kellie Larsen, Mehmet S. Tabak, Aydin Arici, Frederick Schatz, Charles J. Lockwood, Umit A. Kayisli
      Abstract: ProblemThe role of extracellular signal-regulated kinase (ERK)1/2-mediated angiogenesis during endometriotic nidation is unknown. We posit that ERK1/2-induced angioblast differentiation and proliferation promotes ectopic endometrial angiogenesis.Methods of studyHuman eutopic and ectopic endometria were immunostained for total- (T-) or phosphorylated- (P-) ERK1/2 or double-immunostained for P-ERK1/2-CD34 and PCNA-CD34. Estradiol (E2), cytokines, normal peritoneal fluid (NPF) or endometriotic peritoneal fluid (EPF) ±PD98059, an ERK1/2 inhibitor, treaded primary human endometrial endothelial cells (HEECs) were evaluated by T-/P-ERK1/2 immunoblotting, MTT viability and tube formation assays.ResultsHEECs exhibited higher endothelial P-ERK1/2 immunoreactivity in ectopic vs eutopic endometria. Double-immunostained ectopic endometria displayed abundant CD34-positive angioblasts exhibiting strong P-ERK1/2 and PCNA immunoreactivity. EPF and vascular growth factor (VEGF)-A significantly increased HEEC proliferation and P-ERK1/2 levels. PD98059 reduced basal, EPF, and VEGF-induced HEEC proliferation and promoted vascular stabilization following tube formation.ConclusionEnhanced ERK1/2 activity in angioblasts by such peritoneal factors as VEGF, E2 induces proliferation to trigger ectopic endometrial angiogenesis.Increased ERK1/2 phosphorylation (P-ERK1/2) is involved in endothelial progenitor cell (angioblast) differentiation and proliferation in endometriosis. Several individual cells (asterisks) and cell clusters of vascular like structures (presumptive vessels; arrows) display the strongest P-ERK1/2 immunoreactivity in the ectopic endometrium, whereas endothelial cells in distal to ectopic tissue (arrowheads) exhibit weak to moderate P-ERK1/2 immunoreactivity (A, B). CD34, an angioblast marker and P-ERK1/2 double immunostaining is seen in ectopic endometrial specimens (C-E) with stronger P-ERK1/2 (brown) immunoreactivity in CD34 immunoreactive (red) endothelial progenitor cells (arrows; C or D) vs. mature vascular endothelial cells (arrowheads in C or E). Representative photomicrographs of CD34 and PCNA double immunostained ectopic endometrial specimens display stronger co-expression of CD34 (red) and PCNA (brown) in endothelial progenitor cells (arrows; F) than in mature vascular endothelial cells (arrowheads; G), indicating proliferative nature of this CD34 immunoreactive angioblasts.
      PubDate: 2017-09-16T06:21:11.284088-05:
      DOI: 10.1111/aji.12760
  • CCL19/CCR7 contributes to the pathogenesis of endometriosis via PI3K/Akt
           pathway by regulating the proliferation and invasion of ESCs
    • Authors: Ruiying Diao; Weixia Wei, Jinghui Zhao, Fuying Tian, Xueyong Cai, Yong-Gang Duan
      Abstract: ProblemThe level of CCL19 increased in the peritoneal fluid of women with endometriosis, but the precise mechanism of CCL19/CCR7 in the pathogenesis of endometriosis remains unknown.MethodsELISA and immunohistochemistry were performed to analyze CCL19/CCR7 expressions in peritoneal fluid and endometrium from women with endometriosis (n = 38) and controls (n = 32). Cell proliferation and transwell invasion assays were applied to detect proliferation and invasion of human endometrial stromal cells (ESCs). Expressions of Bcl2, MMP2, MMP9, and p-AKT/AKT were analyzed by Western blot.ResultsPeritoneal fluid concentration of CCL19 in patients with endometriosis was higher than that in controls. Those patients with moderate/severe endometriosis had significantly higher peritoneal fluid concentrations of CCL19 compared to those with minimal/mild endometriosis. Higher CCL19 and CCR7 were found in the endometrium with endometriosis compared to control. CCL19 significantly enhanced ESC proliferation and invasion through CCR7 via activating PI3K/Akt signal pathways. CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, Bcl2, MMP2, and MMP9 in ESCs.ConclusionThese data indicate CCL19/CCR7 contributes to proliferation and invasion of ESCs, which are conducive to the pathogenesis of endometriosis through activating PI3K/Akt pathway.
      PubDate: 2017-08-30T04:35:46.691006-05:
      DOI: 10.1111/aji.12744
  • Cortisol inhibits CSF2 and CSF3 via DNA methylation and inhibits invasion
           in first-trimester trophoblast cells
    • Authors: Arianna Smith; Elizabeth Witte, Devin McGee, Jason Knott, Kavita Narang, Karen Racicot
      Abstract: ProblemHeightened maternal stress affects trophoblast function and increases risk for adverse pregnancy outcomes.Methods of StudyStudies were performed using the first-trimester trophoblast cell line, Sw.71. Cytokines were quantified using qPCR and ELISA. Epigenetic regulation of cytokines was characterized by inhibiting histone deacetylation (1 μmol/L suberoylanilide hydroxamic acid [SAHA]) or methylation (5 μmol/L 5-azacytidine), or with chromatin immunoprecipitation (ChIP) with a pan-acetyl histone-3 antibody. Invasion assays used Matrigel chambers.ResultsCortisol inhibited expression of CSF2 (GM-CSF) and CSF3 (G-CSF) in trophoblast cells. Cortisol-associated inhibition was dependent on DNA methylation and was not affected by acetylation. There was also a modest decrease in trophoblast invasion, not dependent on loss of CSFs.ConclusionIn first-trimester trophoblast cells, the physiological glucocorticoid, cortisol, inhibited two cytokines with roles in placental development and decreased trophoblast invasion. Cortisol-associated changes in trophoblast function could increase the risk for immune-mediated abortion or other adverse pregnancy outcomes.
      PubDate: 2017-08-28T06:45:22.884855-05:
      DOI: 10.1111/aji.12741
  • Issue Information
    • PubDate: 2017-08-17T06:00:26.91155-05:0
      DOI: 10.1111/aji.12574
  • Obituary: Leif Matthiesen, MD, PhD (1954-2017)
    • Authors: Surendra Sharma; Goran Berg, Jan Ernerudh
      PubDate: 2017-08-08T04:50:57.870693-05:
      DOI: 10.1111/aji.12740
  • Vitamin D deficiency in an Italian cohort of infertile women
    • Authors: Paola Triggianese; Abdulla Watad, Francesca Cedola, Carlo Perricone, Howard Amital, Ilio Giambini, Roberto Perricone, Yehuda Shoenfeld, Caterina De Carolis
      Abstract: ProblemThe purpose of this study was to explore whether vitamin D might be a marker of female primary infertility in association with the presence of autoimmune diseases (ADs).MethodsThe study was a cross-sectional descriptive study in consecutive outpatients of the Polymedical Center for Prevention of Recurrent Spontaneous Abortion (RSA), in Rome, Italy. Women were eligible if they received a diagnosis of primary infertility or RSA. Serum vitamin D, calcium, and PTH were analyzed.ResultsWomen with primary infertility (n=70) or RSA/non-infertile (n=105) were enrolled; controls (n=250) were included. Infertile women presented lower vitamin D (P=0.03) and higher prevalence of AD (P=0.007) than non-infertile women. In the multivariate analysis, the presence of ADs is associated with higher odds of infertility (OR=2.2), while normal vitamin D was a protective factor (OR=0.9).ConclusionWe described that having vitamin D deficiency and suffering from an AD are independent risk factors for women primary infertility. Supplementation of vitamin D might be useful for pregnancy outcome.
      PubDate: 2017-08-03T04:25:21.204755-05:
      DOI: 10.1111/aji.12733
  • Intrauterine delivery of subunit vaccines induces a systemic and mucosal
           immune response in rabbits
    • Authors: Jonathan Alexander Pasternak; Glenn Hamonic, Nikki M. Forsberg, Colette L. Wheler, Michael K. Dyck, Heather L. Wilson
      Abstract: ProblemMucosal vaccines have long been sought after to improve protection though the production of both a mucosal and systemic immune response, and are thought to be particularly effective at the site of induction. Development of such vaccines has, however, been delayed by the general propensity to develop immune tolerance to antigens encountered at mucosal sites. This study aimed to determine whether an appropriately formulated subunit vaccine delivered to the uterine lumen would effectively trigger induction of immunity over tolerance.MethodsOvalbumin (OVA), truncated glycoprotein D (tGD) from bovine herpesvirus, and a fusion protein of porcine parvovirus VP2 and bacterial thioredoxin (rVP2-TrX) were each formulated with a tri-adjuvant combination of Poly(I : C) (PIC), a host defense peptide (HDP), and a polyphosphazene (PCEP). A single dose of vaccine was delivered either intramuscularly (IM) or into the uterine lumen of intact female rabbits, and the humoral response subsequently evaluated both systemically and at local and distal mucosal sites.ResultsVaccination through either route-induced antigen-specific humoral responses systemically and within the local (uterus) and distal mucosa (lungs and vagina). The observed mucosal response was not compartmentalized to, or within, the upper genital tract and the degree of response appeared to be at least in part antigen dependant.ConclusionThe results of this study provide proof of principle that the uterus can be used as an induction site for subunit vaccination and that vaccine formulation with appropriate adjuvants can trigger both systemic and mucosal immunity when administered IM or into the uterine lumen.To evaluate the comparative immuno-repressiveness of the upper genital tract, subunit vaccines composed a tri-adjuvant combo with either Ovalbumin, truncated glycoprotein D or parvovirus-thioredoxin fusion protein, were delivered either via the intramuscular (IM) or intrauterine (IU) routes. The resulting antigen specific serum titers suggest both delivery sites are equally responsive.
      PubDate: 2017-08-03T04:06:00.763963-05:
      DOI: 10.1111/aji.12732
  • Predicting NK cell subsets using gene expression levels in peripheral
           blood and endometrial biopsy specimens
    • Authors: Michael L. Davies; Svetlana V. Dambaeva, Dimantha Katukurundage, Miroslava Repak, Alice Gilman-Sachs, Joanne Kwak-Kim, Kenneth D. Beaman
      Abstract: ProblemIn molecular analysis of tissue biopsy specimens, one crucial aspect is characterization of immune cell populations. This is especially important for evaluation of uterine receptivity by assessing levels of lymphocyte populations including CD56bright CD16- uterine NK cells and CD56dim CD16+ conventional NK cells. Our objective was to investigate whether measuring total RNA transcripts from a tissue specimen would accurately reflect immune cell levels and be a new technique to assess immune cell subsets.Method of StudyPeripheral blood mononuclear cells (PBMCs) and endometrial tissues were used. Flow cytometry was utilized for the analysis of lymphocyte subsets in PBMCs, and RT-qPCR was applied to quantify RNA transcripts indicative of lymphocyte and granulocyte populations.ResultsIn PBMC specimens, there were significant correlations between gene expression levels and cell subsets. NK cells correlated with CD16A, NKp46, and CD56 transcripts, B cells correlated with EBF1, and CD8+ T cells correlated with CD8β. Finally, endometrial tissues displayed high CD56 expression and very low CD3ε, CD16A, and NKp30, reflecting the characteristic endometrial NK cell subsets.ConclusionStrong correlations between RT-qPCR data and levels of lymphocyte subsets indicate that gene expression analysis will be a useful technique for characterizing levels of CD56+ cells in endometrial tissues.
      PubDate: 2017-08-03T04:01:08.706384-05:
      DOI: 10.1111/aji.12730
  • Diversity of progesterone action on lipopolysaccharide-induced expression
           changes in cultured human cervical fibroblasts according to inflammation
           and treatment timing
    • Authors: Yoshimitsu Kuwabara; Akira Katayama, Sachiko Kurihara, Marie Ito, Mirei Yonezawa, Nozomi Ouchi, Ryuhei Kurashina, Tomoko Ichikawa, Rintaro Sawa, Akihito Nakai, Hideo Orimo, Toshiyuki Takeshita
      Abstract: ProblemThe effectiveness of progesterone (P4) treatment for preventing preterm births is unclear. Its effects on the uterine cervix were tested using cultured human uterine cervical fibroblasts (UCFs).Method of studyUCFs were incubated with lipopolysaccharide (LPS) in the presence or absence of P4 under various conditions. mRNA was subjected to PCR arrays and real-time RT-PCR to assess IL-6, IL-8, IL-1beta, PTGS2, MMP-1, and CXCL10 expression.ResultsWhen exposed to a high-LPS concentration (2.0 μg/mL), expression of these genes was not suppressed by simultaneous P4 (1.0 μmol/L) treatment, but it was significantly inhibited when P4 was administered 1 hour prior to LPS, with the exception of the chemokines IL-8 and CXCL10. Expression of all genes was restricted by P4 under low-level LPS (0.2 μg/mL) stimulation, especially when administered prior to LPS treatment.ConclusionThese data suggest that early or prophylactic P4 administration is an effective and important measure for reducing preterm birth risk.
      PubDate: 2017-08-01T07:04:12.554458-05:
      DOI: 10.1111/aji.12731
  • Placental pericytes and cytomegalovirus infectivity: Implications for HCMV
           placental pathology and congenital disease
    • Authors: David M. Aronoff; Hernan Correa, Lisa M. Rogers, Ravit Arav-Boger, Donald J. Alcendor
      Abstract: ProblemPlacental pericytes are essential for placental microvascular function, stability, and integrity. Mechanisms of human cytomegalovirus (HCMV) pathogenesis incorporating placental pericytes are unknown.Method of StudyHCMV-infected placental tissue was stained by dual-labeled immunohistochemistry. Primary placental pericytes, cytotrophoblasts, and villous fibroblasts were exposed to HCMV; and infectivity was analyzed by microscopy and immunofluorescence. Cytokine expression was examined by Luminex assay. A HCMV-GFP recombinant virus was used to examine replication kinetics.ResultsImmunohistochemistry showed HCMV in trophoblast and the villous core with T-cell and macrophage infiltration. Primary HCMV isolate from a patient (SBCMV)- infected pericytes showed dysregulation of proinflammatory and angiogenic cytokines when compared to control cells. A tri-cell model of the villous floor showed a unique expression profile. Finally, we show pericytes infected in vivo with HCMV in placental tissue from a congenitally infected child.ConclusionPlacental pericytes support HCMV replication, inducing proinflammatory and angiogenic cytokines that likely contribute to viral dissemination, placenta inflammation, and dysregulation of placental angiogenesis.Proinflammatory infiltrate at sites of HCMV infection in placental tissue. Paraffin embedded placental tissue from a neonate infected with CMV. (A, B) Cells dual stained by IHC for T-cells with CD3 antibody (brown/white arrows) and CMV with antibodies to the major immediate early genes (MIE), (red/black arrows) (C, D) cells dual stained by IHC for macrophages with CD68 antibody (brown/white arrows) and CMV with antibodies to the major immediate early genes (MIE), (red/black arrows). Scale bar=100 μm.
      PubDate: 2017-07-25T05:11:11.899237-05:
      DOI: 10.1111/aji.12728
  • Amniotic fluid neutrophils can phagocytize bacteria: A mechanism for
           microbial killing in the amniotic cavity
    • Authors: Nardhy Gomez-Lopez; Roberto Romero, Valeria Garcia-Flores, Yi Xu, Yaozhu Leng, Ali Alhousseini, Sonia S. Hassan, Bogdan Panaitescu
      Abstract: ProblemNeutrophils are capable of performing phagocytosis, a primary mechanism for microbial killing. Intra-amniotic infection is characterized by an influx of neutrophils into the amniotic cavity. Herein, we investigated whether amniotic fluid neutrophils could phagocytize bacteria found in the amniotic cavity of women with intra-amniotic infection.MethodsAmniotic fluid neutrophils from women with intra-amniotic infection were visualized by transmission electron microscopy (n=6). The phagocytic activity of amniotic fluid neutrophils from women with intra-amniotic infection and/or inflammation (n=10) or peripheral neutrophils from healthy individuals (controls, n=3) was tested using ex vivo phagocytosis assays coupled with live imaging. Phagocytosis by amniotic fluid neutrophils was also visualized by confocal microscopy (n=10) as well as scanning and transmission electron microscopy (n=5).Results(i) Intra-amniotic infection-related bacteria including cocci (eg Streptococcus agalactiae), bacilli (eg Bacteriodes fragilis and Prevotella spp.), and small bacteria without a cell wall (eg Ureaplasma urealyticum) were found inside of amniotic fluid neutrophils; (ii) peripheral neutrophils (controls) rapidly phagocytized S. agalactiae, U. urealyticum, Gardnerella vaginalis, and Escherichia coli; (iii) amniotic fluid neutrophils rapidly phagocytized S. agalactiae and G. vaginalis; and (iv) amniotic fluid neutrophils slowly phagocytized U. urealyticum and E. coli; yet, the process of phagocytosis of the genital mycoplasma was lengthier.ConclusionAmniotic fluid neutrophils can phagocytize bacteria found in the amniotic cavity of women with intra-amniotic infection, namely S. agalactiae, U. urealyticum, G. vaginalis, and E. coli. Yet, differences in the rapidity of phagocytosis were observed among the studied microorganisms. These findings provide a host defense mechanism whereby amniotic fluid neutrophils can kill microbes invading the amniotic cavity.Amniotic fluid neutrophils can phagocytize bacteria, including Streptococcus agalactiae. (A) A scanning electron microscopy image of S. agalactiae. Magnification 10 000X. (B) A scanning electron microscopy image of amniotic fluid neutrophils and S. agalactiae (red arrow) prior to phagocytosis. Magnification 6000X. (C) Confocal microscopy images showing bacteria ingested by amniotic fluid neutrophils (white arrows). Separated images show DAPI staining in blue, CD15 (a neutrophil marker) in red, bacteria in green, and a merged image. Magnification 630X. (D) A transmission electron microscopy image of a neutrophil engulfing S. agalactiae. Magnification 2500X. Red arrows identify bacteria ingested by amniotic fluid neutrophils.
      PubDate: 2017-07-13T01:50:53.60412-05:0
      DOI: 10.1111/aji.12723
  • A novel in vitro model of villitis of unknown etiology demonstrates
           altered placental hormone and cytokine profile
    • Authors: Hayley Derricott; Alexander E.P. Heazell, Susan L. Greenwood, Rebecca L. Jones
      Abstract: ProblemPlacental dysfunction is present over 50% of cases of stillbirth and fetal growth restriction (FGR). Villitis of unknown etiology (VUE), an inflammatory condition of the placenta characterized by maternal T cell infiltrates in the villous stroma and dysregulation of inflammatory cytokines, is more frequent in FGR and stillbirth.Method of studyA novel in vitro model of placental inflammation was developed to test the hypothesis that inflammatory cells seen in VUE and/or cytokines impair placental function.ResultsCoculture of placental explants with maternal leukocytes resulted in increased leukocytes in villous tissue and elevated concentrations of IL-1β, IL-1Ra, IL-6, IL-10, and IFN-γ (P≤.05). Human chorionic gonadotrophin secretion was reduced following coculture with leukocytes (P≤.01) and cytokines (P≤.05).ConclusionThese observations support the hypothesis that altered placental inflammation has deleterious effects on placental function. This model could be used to further understanding about the pathophysiology of VUE and to test potential therapies.In an in vitro model of villitis of unknown etiology maternal T cells can be seen invading villus tissue explants (A). Maternal T cells labeled with Cell Tracker fluorescence (B and C) are observed in the intervillus space. (D) Control explant cultured without T cells.
      PubDate: 2017-07-06T04:25:28.136126-05:
      DOI: 10.1111/aji.12725
  • Proliferation of endogenous regulatory T cells improve the pathophysiology
           associated with placental ischaemia of pregnancy
    • Authors: Tarek Ibrahim; Lukasz Przybyl, Ashlyn C. Harmon, Lorena M. Amaral, Jessica L. Faulkner, Denise C. Cornelius, Mark W. Cunningham, Thomas Hünig, Florian Herse, Gerd Wallukat, Ralf Dechend, Babbette LaMarca
      Abstract: ProblemPreeclampsia (PE) is associated with inflammation and decreased Treg cells and IL-10. The reduced uterine perfusion pressure (RUPP) rat model of PE exhibits these characteristics, and we hypothesized that induction of endogenous Tregs by a specific stimulus (CD28 superagonistic monoclonal antibody) would reduce inflammation, vasoactive factors, and hypertension in RUPP rats.Method of studyRUPP was performed at gestation day (GD) 14; CD28 superagonist was administered intraperitoneally GD15; GD18 carotid catheters were inserted, and GD19 MAP and pup weight, blood, and tissues were collected.ResultsMAP (mmHg) in NP rats was 99±5 and 122±2 in RUPPs and was 111±1 mmHg in RUPP+SA. Circulating Tregs were 6±2% in NP rats and 0.77±0.49% in RUPP rats but increased to 11± 3% in RUPP+SA rats. Circulating IL-6 and IL-2 were decreased while IL-10 and TGF-B were significantly increased in RUPP+SA compared to RUPP controls. Vasoactive pathways such as ET-1, AT1-AA, and ROS were all reduced in RUPP+SA compared to RUPP. Pup weight was 2.4±0.05 mg in NP and 1.94±0.062 mg in RUPP and increased to 2.1± 0.05 mg in RUPP+SA.ConclusionThese data suggest that stimulating endogenous Tregs lower factors causing hypertension and can improve fetal weight in response to PE.
      PubDate: 2017-07-06T03:55:20.697295-05:
      DOI: 10.1111/aji.12724
  • Increased expression of resistin in ectopic endometrial tissue of women
           with endometriosis
    • Authors: Yoon Kyung Oh; Young Ran Ha, Kyong Wook Yi, Hyun Tae Park, Jung-Ho Shin, Tak Kim, Jun-Young Hur
      Abstract: ProblemInflammation is a key process in the establishment and progression of endometriosis. Resistin, an adipocytokine, has biological properties linked to immunologic functions, but its role in endometriosis is unclear.Method of studyResistin gene expression was examined in eutopic and ectopic endometrial tissues from women with (n=25) or without (n=25) endometriosis. Resistin mRNA and protein levels were determined in endometrial tissue using quantitative real-time reverse transcription PCR and Western blotting, following adipokine profiling arrays.ResultsResistin protein was detected in human endometrial tissues using an adipokine array test. Resistin mRNA and protein levels were significantly higher in ectopic endometrial tissue of patients with endometriosis than in normal eutopic endometrial tissue.ConclusionOur results indicate that resistin is differentially expressed in endometrial tissues from women with endometriosis and imply a role for resistin in endometriosis-associated pelvic inflammation.Resistin mRNA expression is significantly higher in ectopic endometrial tissues of patients with endometriosis than in eutopic endometrial tissues of women without disease.
      PubDate: 2017-07-06T03:35:36.088658-05:
      DOI: 10.1111/aji.12726
  • The role of regulatory T cells in thymectomy-induced autoimmune ovarian
    • Authors: Yajun Dong; Hongmei Li, Yuyan Li, Yonggang Liu, Huiling Chen, Pingping Xu, Tingting Zhao, Wei He
      Abstract: ProblemTo evaluate the role of regulatory T (Treg) cells in autoimmune ovarian disease (AOD).Method of studyAOD model was set up by thymectomy of BALB/C mice on day 3 (d3tx). The variation of T lymphocyte subsets, especially the Treg cells were analyzed in the peripheral blood, spleen, para-aortic, and inguinal lymph nodes in d3tx mice. The effect of Treg cells on AOD was further evaluated by adoptive transfer of Treg cells into d3tx mice (d3tx+Treg).ResultsIn d3tx mice, the ratio of Treg/CD4+ was significantly increased rapidly from 1st to 2nd week, rapidly declined in 3rd week, then decreased slowly until the 9th week. The CD3+/T lymphocytes and the ratio of CD4+/CD3+ were significantly decreased in the para-aortic and inguinal lymph nodes of d3tx mice, but the ratio of Treg/CD4+ and CD8+/CD3+ were increased simultaneously. In d3tx mice with adoptive transfer of Treg cells (0.5×104~5×105), there was a significant increase in the Treg/CD4+ ratios in the spleen and peripheral blood. AOD score, especially adoptive transferred treg cells from the ovarian lymph nodes was significantly decreased. Oocytes were successfully obtained from d3tx+Treg mice, which could fertilize and develop to embryos normally.ConclusionTreg cells involved in the pathogenesis of AOD. Sufficient numbers of Treg cells can modify AOD in the early phase in d3tx mice.
      PubDate: 2017-06-29T01:26:19.281138-05:
      DOI: 10.1111/aji.12683
  • Identification of genes dysregulated by elevation of microRNA-210 levels
           in human trophoblasts cell line, Swan 71
    • Authors: Sejin Ahn; Eunbee Jeong, Jae Woong Min, Eunhee Kim, Sun Shim Choi, Chong Jae Kim, Deug-Chan Lee
      Abstract: ProblemPreeclampsia is a serious pregnancy disorder characterized by gestational hypertension and proteinuria. miR-210 is significantly overexpressed in the placentas of preeclampsia patients.Method of studySwan 71 cells, first-trimester human trophoblastic cell line, were transfected with hsa-miR-210-3p oligonucleotides by electroporation. Altered transcriptome was analyzed using microarray technique. Differentially expressed genes (DEGs) were clustered into Gene Ontology annotation biological processes. The extent of physical interaction between miR-210 and IGFBP3 mRNA was assessed via ribonucleoprotein immunoprecipitation.ResultsMicroarray analysis showed 408 DEGs by elevated levels of miR-210 in Swan 71 cells. These genes were enriched in several biological processes involved in the pathogenesis of preeclampsia. IGFBP3, a gene associated with preeclampsia pathophysiology, was validated as a target gene of miR-210.ConclusionWe have demonstrated that elevated miR-210 levels in human trophoblast alter the expression profile of known preeclampsia-associated genes, and of gene targets involved in various biological processes essential to preeclampsia progression.
      PubDate: 2017-06-27T01:13:20.969468-05:
      DOI: 10.1111/aji.12722
  • Prior pregnancy and antenatal rubella sero-negativity—evidence of
           persistent maternal immunologic alteration'
    • Authors: Terence T. Lao; Annie S. Y. Hui, Daljit S. Sahota
      Abstract: ProblemIt is unclear if the immunologic alterations induced by pregnancy could persist.Method of studyAntenatal rubella sero-negativity was correlated with gravidity, abortions and parity in 112 083 gravidae managed during 1997-2015, with further analysis stratified for factors known to influence rubella serology.ResultsThe 10.2% sero-negative gravidae had different characteristics, and the incidence showed significant difference and positive trend (P
      PubDate: 2017-06-27T00:47:51.519245-05:
      DOI: 10.1111/aji.12727
  • Uterine natural killer cells in patients with idiopathic recurrent
    • Authors: Ruben-J. Kuon; Maja Weber, Julia Heger, Isabel Santillán, Kilian Vomstein, Christin Bär, Thomas Strowitzki, Udo R. Markert, Bettina Toth
      Abstract: ProblemUterine natural killer (uNK) cells are major players during implantation and early pregnancy. The aim of our study was to analyze uNK cell concentration in the endometrium of idiopathic recurrent miscarriage (iRM) patients and fertile controls.Method of studyOut of n=130 couples with ≥3 consecutive, clinical RM screened according to a standardized diagnostic protocol, n=58 patients with iRM were identified. Endometrial biopsies were investigated in patients and n=17 fertile women (controls) via immunohistochemistry.ResultsCompared to controls, the concentration of uNK cells was significantly higher in iRM patients (257±212 vs. 148±73 uNK cells/mm², P=.04). IRM patients showed a higher prevalence of>300 uNK cells/mm² than controls (34.5% vs. 5.9%, P=.02). In 88% of controls and 62% of iRM patients, uNK cells were detected within the range of 40-300/mm².ConclusionIdiopathic recurrent miscarriage patients showed higher uNK cell levels than controls supporting the possible impact of uNK cells in the pathophysiology of miscarriage. Our cutoff levels might help to select RM patients which may benefit from immunomodulatory treatment.
      PubDate: 2017-06-21T23:07:03.918915-05:
      DOI: 10.1111/aji.12721
  • An investigation of the relationship between recurrent spontaneous
           abortion and memory T follicular helper cells
    • Authors: Xiaorui Luan; Xiaomin Kang, Weiping Li, Qian Dong
      Abstract: ProblemImmune tolerance with respect to a semi-allogeneic fetus plays a key role in the establishment of a pregnancy. Memory T follicular helper (Tfh) cells have a central role in the regulation of the adaptive immune response. Much of our knowledge of memory Tfh cells’ function comes from immune-related diseases. However, the true physiological characteristics of memory Tfh cells and their mode of action in pregnancy remain unclear.Methods of studyDeciduas and blood were obtained from 25 recurrent spontaneous abortion (RSA) patients undergoing surgical abortion and 19 normal women in early pregnancy undergoing elective termination. RSA patients were grouped into antibody-positive patients and antibody-negative patients, respectively. The memory Tfh cells with the CD4+CXCR5+PD1+CCR7− and CD4+CXCR5+PD-1+ICOS+ phenotypes were assessed by flow cytometry. The B cells were evaluated by flow cytometry. A correlation analysis of the subsets of memory Tfh cells and B cells in antibody-positive RSA patients was made by the Pearson test.ResultsMemory Tfh cells with the CD4+CXCR5+PD1+CCR7− and CD4+CXCR5+PD-1+ICOS+ phenotypes showed a significant increase in RSA patients compared to women with a normal pregnancy who had chosen termination. When RSA patients were grouped according positive or negative antibodies, it was surprising to find that decidual CD4+CXCR5+PD-1+ICOS+ memory Tfh cells significantly increased in RSA patients with positive antibody compared to RSA patients with negative antibody. However, the percentages of CD4+CXCR5+PD1+CCR7− memory Tfh cells did not change in the deciduas of the two groups. Circulating and decidual B cells significantly increased in antibody-positive RSA patients compared with antibody-negative RSA patients. Correlation analysis indicated a strong association between the decidual CD4+CXCR5+ PD-1+ ICOS+ memory Tfh cells and B cells in antibody-positive RSA patients.ConclusionThese new findings provide unique insights into memory Tfh cells in mediating feto-maternal immune tolerance.
      PubDate: 2017-06-21T23:06:00.031253-05:
      DOI: 10.1111/aji.12714
  • PlGF enhances TLR-dependent inflammatory responses in human mononuclear
    • Authors: Laura F. Newell; Shernan G. Holtan, Jane E. Yates, Leonardo Pereira, Jeffrey W. Tyner, Irina Burd, Grover C. Bagby
      Abstract: ProblemLevels of placental growth factor (PlGF) peak during third trimester of pregnancy, a time when women are at increased risk of virus-induced morbidity. We hypothesized PlGF might contribute to an exaggerated inflammatory response to Toll-like receptor (TLR) activation.Method of studyPrimary human adult and cord blood CD14+ cells were cultured in the presence of TLR ligands and/or PlGF.ResultsPlGF significantly enhanced the magnitude and duration of TNF messenger RNA and protein production by TLR-7/8-activated monocytes, and increased subsequent production of TNF-independent inflammatory cytokines. This PlGF/TLR effect involved multiple inflammatory cytokines/chemokines and was seen with the majority of TLR agonists. PlGF enhanced phosphorylation of IkappaB kinase (IKK) in monocytes stimulated with the TLR-7/8 agonist R848, and IKK inhibition completely suppressed the PlGF effect.ConclusionPlGF enhances TLR-signaling upstream of IKK and contributes to an exaggerated pathologic pro-inflammatory state in response to activation of maternal and fetal mononuclear phagocytes by specific TLR agonists.
      PubDate: 2017-06-20T23:20:53.410267-05:
      DOI: 10.1111/aji.12709
  • Live birth rate following oral antibiotic treatment for chronic
           endometritis in infertile women with repeated implantation failure
    • Authors: Kotaro Kitaya; Hidehiko Matsubayashi, Yukiko Takaya, Rie Nishiyama, Kohei Yamaguchi, Takumi Takeuchi, Tomomoto Ishikawa
      Abstract: ProblemThe aim of this prospective study was to investigate the prevalence of chronic endometritis (CE) in infertile women with a history of repeated implantation failure (RIF) and to determine whether oral antibiotic treatment improves their live birth rate in the following embryo transfer (ET) cycles.Method of studyEndometrial biopsy samples obtained from infertile women with RIF were subjected to immunohistochemistrical/histopathologic diagnosis of CE. Following antibiotic administration to the RIF/CE group, their histopathologic cure rate, microbial detection rate, and reproductive outcome in the subsequent ET cycles were prospectively studied.Results33.7% of infertile women with RIF were diagnosed with CE. Following the first-line doxycycline treatment, the histopathologic cure rate in the subsequent endometrial biopsy was 92.3%. Following the second-line metronidazole/ciprofloxacin treatment, the overall cure rate was 99.1%. The live birth rate in the first ET cycle (P=.031, RR 1.48, 95% CI 1.03-2.12) and cumulative three ET cycles (P=.037, RR 1.39, 95% CI 1.02-1.90) following antibiotic treatment in the cured RIF/CE group (32.8% and 38.8%, respectively) was significantly higher than in the RIF/non-CE group (22.1% and 27.9%, respectively).ConclusionChronic endometritis was found in one-third of infertile women with RIF. The oral antibiotic treatment against CE might be a promising therapeutic option for infertile women with RIF.
      PubDate: 2017-06-13T04:40:19.34315-05:0
      DOI: 10.1111/aji.12719
  • Toll-like receptor4 as a modulator of fertilization and subsequent
           pre-implantation development following in vitro maturation in mice
    • Authors: Sara Hosseini; Maryam Dehghani-Mohammadabadi, Marefat Ghafarri Novin, Mostafa Haji Molla Hoseini, Ehsan Arefian, Samira Mohammadi Yeganeh, Mohammad Salehi
      Abstract: ProblemThe use of in vitro maturation (IVM) as an alternative approach to the conventional assisted reproductive technique in clinical practice is limited due to low fertilization rate. The expression of Toll-like receptors (TLRs) as members of an innate immune system in cumulus cells are thought to affect fertilization. This study was aimed to evaluate the effect of IVM on TLR4 gene expression and fertilization rate in oocytes derived from IVM in comparison with in vivo matured one.Method of studyCumulus cells are collected from oocytes derived IVM and in vivo. The expression level of Tlr4 in cumulus cells of both groups was assessed by quantitative real-time PCR. To examine the protein expression level of TLR4, immunocytochemistry and Western blotting techniques were carried out. TLR4 receptor functions were also confirmed by blockade assay and TLR4 receptor activation with lipopolysaccharide.ResultThere was a substantial decrease in fertilization and blastulation rate in the IVM group in comparison with the in vivo one. The mRNA expression and protein levels of TLR4 declined in cumulus cells following IVM. Anti-TLR4 blocking antibody dramatically decreased the rate of fertilization and blastocyst formation compared to the in vivo group. In contrast, the fertilization rate was enhanced significantly in the presence of LPS as a TLR4 ligand compared to the control group.ConclusionLow expression level of Tlr4 following IVM and higher fertilization rate through TLR4 receptor activation with LPS proposed that alteration in TLR4 expression and subsequent cytokine section could be a possible cause of low fertilization rate in IVM-derived oocytes.
      PubDate: 2017-06-13T02:25:24.583468-05:
      DOI: 10.1111/aji.12720
  • Soluble CEACAM1 and CEACAM6 are differently expressed in blood serum of
           pregnant women during normal pregnancy
    • Authors: Pawel Mach; Alexandra Gellhaus, Sebastian Prager, Tom Moore, Gunther Wennemuth, Rainer Kimmig, Angela Köninger, Bernhard B. Singer
      Abstract: ProblemCEACAM1 and CEACAM6 belong to the carcinoembryonic antigen (CEA) family and may play an immune-modulatory role during pregnancy. The aim of the study was to determine the blood serum levels of soluble CEACAM1 and CEACAM6 over the course of pregnancy and postpartum.Method of studyCEACAM1 and CEACAM6 levels were determined with customized in-house Sandwich-enzyme-linked immunosorbent assay (ELISA) systems. The study population (n=125) was divided into four groups according to the pregnancy trimester and postpartum. Additionally, samples of non-pregnant women (n=14) were analyzed.ResultsSerum levels of CEACAM1 in healthy pregnant women were much lower than in non-pregnant women, a difference not seen for CEACAM6. Comparison between the trimesters and postpartum revealed a significant difference in CEACAM1 serum levels. The highest CEACAM1 levels were detected in third trimester. These levels were statistically significantly different from the CEACAM1 levels in first trimester and second trimester. The lowest levels were observed in the second trimester. Postpartum CEACAM1 serum concentrations were slightly lower than in the third trimester, but higher than in the first trimester and significantly higher compared to levels in the second trimester.ConclusionDecreased concentration of CEACAM1 during the pregnancy suggests its regulatory role in the immune tolerance during the course of pregnancy.
      PubDate: 2017-06-08T00:45:30.135232-05:
      DOI: 10.1111/aji.12700
  • APOBEC3G is increasingly expressed on the human uterine cervical
           intraepithelial neoplasia along with disease progression
    • Authors: Takashi Iizuka; Kousho Wakae, Mitsuhiro Nakamura, Koichi Kitamura, Masanori Ono, Hiroshi Fujiwara, Masamichi Muramatsu
      Abstract: ProblemAPOBEC3G (A3G) is a cytidine deaminase that exhibits antiviral activity by introducing C-to-T hypermutation in viral DNA. We recently observed the distinct presence of C-to-T hypermutation of human papillomavirus DNA in uterine cervical intraepithelial neoplasia (CIN), suggesting the possible involvement of A3G in the mutation-inducing process. Consequently, we investigated the association of A3G expression with CIN progression in this study.Method of studyPatients who had undergone cervical conization due to CIN1 (n=11), CIN2 (n=9), CIN3 (n=12), and micro-invasive squamous cell carcinoma (n=2) were included. The expression profiles of A3G and p16 proteins in cervical lesions and A3G-positive immune cells around the lesions were examined by immunohistochemistry.ResultsImmunoreactive A3G protein was detected in the CIN and squamous cell carcinoma lesions. Its expression intensity and positive areas were increased and spread in accordance with the progression of CIN, respectively. The co-expression of p16 was observed on the A3G-positive atypical cells. The numbers of A3G-positive immune cells in CIN3 lesions were significantly higher than those of CIN1-2 lesions.ConclusionThese findings indicate that A3G is associated with CIN, suggesting its important roles in human papillomavirus-induced pathophysiological processes such as CIN progression and viral elimination.
      PubDate: 2017-06-07T05:55:29.24583-05:0
      DOI: 10.1111/aji.12703
  • Detection of dendritic cells and related cytokines in follicular fluid of
           patients with polycystic ovary syndrome
    • Authors: Tao Zhang; Fuying Tian, Ran Huo, Aifa Tang, Yong Zeng, Yong-Gang Duan
      Abstract: ProblemThe presence of dendritic cells (DCs) and associated cytokines in follicular fluid (FF) from patients with polycystic ovary syndrome (PCOS) remains unknown.Methods of studyFF was collected from PCOS patients and patients with severe male factor infertility (control) at the day of transvaginal oocyte retrieval. Phenotypes of DC were detected by flow cytometry, and TNF-α, IL-6, IL-10, and IL-23 were assessed by ELISA.ResultsA significant decrease in the percentage of DC was found in patients with PCOS (16.22±5.5%) compared with control (21.27±5.5%, P
      PubDate: 2017-06-06T06:40:28.761973-05:
      DOI: 10.1111/aji.12717
  • The cytokine network in women with an asymptomatic short cervix and the
           risk of preterm delivery
    • Authors: Adi L. Tarca; Wendy Fitzgerald, Piya Chaemsaithong, Zhonghui Xu, Sonia S. Hassan, Jean-Charles Grivel, Nardhy Gomez-Lopez, Bogdan Panaitescu, Percy Pacora, Eli Maymon, Offer Erez, Leonid Margolis, Roberto Romero
      Abstract: ProblemTo characterize the amniotic fluid (AF) inflammatory-related protein (IRP) network in patients with a sonographic short cervix (SCx) and to determine its relation to early preterm delivery (ePTD).Method of studyA retrospective cohort study included women with a SCx (≤25 mm; n=223) who had amniocentesis and were classified according to gestational age (GA) at diagnosis and delivery (ePTD
      PubDate: 2017-06-06T06:35:24.179529-05:
      DOI: 10.1111/aji.12686
  • Estradiol and progesterone influence on influenza infection and immune
           response in a mouse model
    • Authors: Sarah M. Davis; Leigh M. Sweet, Karen H. Oppenheimer, Benjamin T. Suratt, Mark Phillippe
      Abstract: ProblemInfluenza infection severity may be mediated by estradiol and/or progesterone.Method of StudyAn exploratory study was designed to evaluate 17-β-estradiol and progesterone on influenza infection and examine immune-mediated response in a mouse model. Inoculation with placebo or mouse-adapted H1N1 influenza virus occurred. Treatment groups included 17-β-estradiol, progesterone, ovariectomy, and pregnancy. Mice were assessed for morbidity and mortality. Toll-like receptor gene studies and airspace cell differentials were performed.ResultsOnset of morbidity was earlier and morbidity duration greater for progesterone. Absence of morbidity/mortality and overall survival was greater for 17-β-estradiol. Airspace cell differentials suggest improved immune cell recruitment for 17-β-estradiol. Pregnant mouse data demonstrate significant mortality during the period of increased progesterone. Select immune cell markers demonstrate patterns of regulation that may promote proper immune response to influenza infection for 17-β-estradiol.ConclusionEstradiol may play a protective and progesterone a detrimental role in the pathophysiology of influenza infection.
      PubDate: 2017-05-30T01:11:16.493347-05:
      DOI: 10.1111/aji.12695
  • Labor prediction based on the expression patterns of multiple genes
           related to cervical maturation in human term pregnancy
    • Authors: Taiki Samejima; Takeshi Nagamatsu, Danny J. Schust, Takayuki Iriyama, Seisuke Sayama, Masaki Sonoda, Atsushi Komatsu, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
      Abstract: ProblemThis study explored the possibility of evaluating cervical maturation using swabbed cervical cell samples at term pregnancy, and aimed to develop a novel approach to predict labor onset.Method of studyWomen with uncomplicated pregnancies (n=117 from 62 women at term pregnancy) were recruited. Messenger RNA expression levels of cervical cells for ten genes were quantified by qPCR. Principal component analysis (PCA) was conducted, and principal components that significantly contributed to the prediction of days to delivery were determined.ResultsPCA demonstrated that 76% of the expression information from the ten genes can be represented by three principal components (PC1-3). By the multiple regression analysis, PC2 and Bishop score but not PC1 or PC3 were significant variables in the prediction of days to delivery.ConclusionThese findings support the concurrent assessment of multiple gene activities in cervical cells as a promising approach to predict the initiation of labor.
      PubDate: 2017-05-30T01:10:58.131788-05:
      DOI: 10.1111/aji.12711
  • Prevention of alloimmunization during pregnancy by prednisone and
           immunoglobulin G—What is the evidence'
    • Authors: Jens Kjeldsen-Kragh
      PubDate: 2017-05-30T01:10:49.71177-05:0
      DOI: 10.1111/aji.12697
  • Abnormal ratio of CD57+ cells to CD56+ cells in women with recurrent
           implantation failure
    • Authors: Ruiwei Jiang; Guijun Yan, Jun Xing, Zhilong Wang, Yong Liu, Hongyan Wu, Xiangshan Fan, Jianjun Zhou, Lijun Ding, Haixiang Sun
      Abstract: ProblemTo define a more precise parameter for a better understanding of natural killer (NK) cells and its relation with regulatory T cells (Tregs) in women with recurrent implantation failure (RIF).Method of studyThe percentages of CD56+ cells, CD57+ cells and Foxp3+ cells in the endometrium and blood from 23 normal controls and 32 women with RIF were measured by immunocytochemistry and flow cytometry.ResultsWomen with RIF had significantly increased ratio of CD57+ cells to CD56+ cells in both the endometrium (P
      PubDate: 2017-05-20T01:15:25.723427-05:
      DOI: 10.1111/aji.12708
  • Peripartum cytokine flares in a multiethnic cohort of chronic hepatitis B
           carriers does not correlate with hepatitis B virus suppression or
           increased risk of liver disease
    • Authors: Shivali S. Joshi; Daniel Wong, Eliana Castillo, Mark G. Swain, Carla S. Coffin
      Abstract: ProblemIn chronic hepatitis B (CHB) carriers, alanine transaminase (ALT) flares are common in the peripartum period. There are limited data on immunological changes of pregnancy in CHB. We hypothesize that in pregnant CHB carriers, the Th1/Th2 cytokine ratio is altered resulting in changes in biochemical/virological and liver fibrosis markers.Study methodsSerum from 38 pregnant/post-partum CHB carriers (median age 32 years, 53% Asian, 8 HBeAg+) was tested for HBV DNA, quantitative HBV surface antigen, ALT and liver fibrosis by transient elastography (TE). Serum cytokines were analyzed using a Luminex assay.ResultsUntreated CHB cases had mild ALT flares post-partum, but showed normal TE, and no change in viral markers despite increased Th1 cytokines compared to healthy controls (P
      PubDate: 2017-05-19T23:50:24.267558-05:
      DOI: 10.1111/aji.12707
  • Elevated maternal placental protein 13 serum levels at term of pregnancy
           in postpartum major hemorrhage (>1000 mLs). A prospective cohort study
    • Authors: Antonio Farina; Dalila Bernabini, Cinzia Zucchini, Paola De Sanctis, Maria Soledad Quezada, Mara Mattioli, Nicola Rizzo
      Abstract: ProblemTo compare placental protein 13 (PP13) levels in the serum of women with primary postpartum hemorrhage (PPH) with a control population.MethodsA prospective cohort study was conducted between May 2014 and May 2016 and included 435 pregnant women at term (38 weeks gestation) without any known risk factor and with normal labor. Multiples of median (MoM) were used to evaluate differences of the PP13 values between cases and controls. PP13 concentrations were adjusted for maternal and neonatal weight. Multivariable analysis was used to detect independent contribution of predictors of PPH.ResultsFifteen had a major PPH>1000 mLs and represented the cases of the study. They were matched with 399 controls. Twenty-one patients who had a minor PPH (500-1000 mLs) were excluded. The mean observed rank in the PPH group was higher than that of controls (28.5 vs 13.5, P-value=.01). PP13 MoM values adjusted for maternal weight were higher than expected being 1.44±0.45 in PPH cases and 1.00±0.59 in controls (P-value .008). This difference was still significant even after adjustment for neonatal weight that represented a confounding variable.ConclusionHigher PP13 levels are independently associated with major PPH>1000 mLs.Relationship between maternal weight (kg) and maternal serum PP13 (expressed as multiples of the median or MoM). The straight line represents the currently used log-linear relationship while the thick curved line shows the power relationship (Y=a. weightb) (F=27.72 P-value
      PubDate: 2017-05-15T23:10:27.701447-05:
      DOI: 10.1111/aji.12702
  • The cross talk between cervical carcinoma cells and vascular endothelial
           cells mediated by IL-27 restrains angiogenesis
    • Authors: Bing Zhang; Feng Xie, Chun-Lin Dong, Chun-Jie Gu, Jiao Cheng, Yuan Wang, Xi-Zhong Xu, Hong Pu, Yi-Bo Wu, Xiao-Wei Qi, Da-Jin Li, Jin-Jin Yu, Ming-Qing Li
      Abstract: ProblemTo explore whether cervical carcinoma cell-derived interleukin-27 (IL-27) modulates the angiogenesis of vascular endothelial cells.Method of studyThe expression of IL-27 in cervical cancer tissues and cervical cell lines was analyzed by immunohistochemistry, ELISA and flow cytometry. Then, the effects of IL-27 on the proliferation and apoptosis-related molecules and angiogenesis in vitro of human umbilical vein endothelial cells (HUVECs) were investigated. Finally, in vivo experiment was performed to further confirm the effects of IL-27.ResultsCompared with cervicitis, the cervical cancer tissues highly expressed IL-27. Both HeLa and CaSki cells secreted IL-27, and HUVECs expressed low levels of IL-27 receptors (IL-27R). However, the co-culture of cervical cell lines and HUVECs led to a significant elevation of IL-27R on HUVECs. Co-culturing with IL-27-overexpressed HeLa cells downregulated Ki-67 and Bcl-2 and upregulated Fas expression in HUVECs. In addition, overexpression of IL-27 in HeLa cells and CasKi cells secreted less IL-8 and could further restrict angiogenesis compared with control cells in vitro. In the subcutaneous tumorous model of C57/BL6 mouse, there were decreased vessel density and tumor volume when inoculation with IL-27-overexpressed TC-1 cells.ConclusionThis study indicates that IL-27 secreted by cervical carcinoma cells restricts the angiogenesis in a paracrine manner in the pathogenesis of cervical cancer.
      PubDate: 2017-05-15T23:05:33.566323-05:
      DOI: 10.1111/aji.12706
  • Increased delta neutrophil index in women with severe preeclampsia
    • Authors: Hee Young Cho; Inkyung Jung, So Jung Kim, Yong Won Park, Young Han Kim, Ja-Young Kwon
      Abstract: ProblemThe pathophysiology of preeclampsia (PE) is believed to be associated with a systemic inflammatory response, but few inflammatory markers are currently available to predict PE. Therefore, the aim of this study was to compare the serum delta neutrophil index (DNI) between normal and preeclamptic women.MethodsSixty-five patients with mild preeclampsia (mPE), 147 patients with severe preeclampsia (sPE), and 163 women with normal pregnancy were included in this study. Maternal laboratory values including DNI were compared among the three groups.ResultsThe mean DNI was significantly higher in the sPE group, but there was no significant difference between the normal pregnancy group and mPE. The DNI also showed positive correlation with systolic and diastolic blood pressures, mean arterial pressure, proteinuria during 24 hours, proteinuria in dipstick, and ominous symptoms.ConclusionThe serum DNI value was increased in women with severe preeclampsia compared to that in those with normal pregnancy or mild preeclampsia. Further studies are needed to evaluate application of the DNI value as a prognostic marker of preeclampsia.
      PubDate: 2017-05-12T05:55:23.812954-05:
      DOI: 10.1111/aji.12705
  • Expression profile of heat shock proteins in placental tissues of patients
           with preterm prelabor rupture of membranes and spontaneous preterm labor
           with intact membranes
    • Authors: Lenka Dvorakova; Katarina Ivankova, Ladislav Krofta, Ilona Hromadnikova
      Abstract: ProblemInvestigating the stress response in the central cotyledon zone of placental tissue in pregnancies with PPROM, PTB, and at term in labor.Method of studyGene expression of Hsp27, Hsp60, Hsp70, Hsp90, and HspBP1 was compared between these particular groups. Correlation between variables including Hsp gene expression in placental tissue and the gestational age at delivery, WBC count at admission, and serum levels of CRP at admission in patients with PPROM and PTB was determined.ResultsBoth PPROM and PTB pregnancies were associated with altered Hsp gene expression profile. While PPROM and PTB always induced upregulation of Hsp27 and Hsp60, downregulation of Hsp70 and HspBP1 was present entirely in patients with PPROM. HspBP1 expression profile was also able to differentiate between PPROM and PTB pregnancies. The highest mRNA levels of Hsp60 and Hsp70 were detected in PTB pregnancies with elevated CRP levels at admission. Some of the examined Hsp displayed increased expression with advancing gestational age in both groups (PPROM: Hsp27, Hsp70, and Hsp90; and PTB: Hsp27).ConclusionUpregulation of Hsp27 is a common phenomenon shared between pregnancies affected with PTB and PPROM. On the other hand, downregulation of Hsp70 and HspBP1 represents a unique feature of PPROM.
      PubDate: 2017-05-12T04:30:58.780345-05:
      DOI: 10.1111/aji.12698
  • Immunosuppressive treatment using tacrolimus promotes pregnancy outcome in
           infertile women with repeated implantation failures
    • Authors: Koji Nakagawa; Joanne Kwak-Kim, Keiji Kuroda, Rikikazu Sugiyama, Koushi Yamaguchi
      Abstract: ProblemWe aim to investigate whether the peripheral blood T helper (Th) 1 cell level could predict pregnancy outcome in patients who have experienced repeated implantation failure (RIF, three or more) after ART cycles.Method of studyThis is a prospective cohort study of total 124 women with RIF who showed elevated Th1/Th2 (CD4+IFN-γ+/CD4+IL-4+) cell ratios (≥10.3) and received tacrolimus at Sugiyama Clinic between November 2011 and July 2016. Patients were divided into three groups as per Th1 cell levels: Th1 level of
      PubDate: 2017-05-03T04:40:25.154853-05:
      DOI: 10.1111/aji.12682
  • Hypoxia-inhibited DUSP2 expression promotes IL-6/STAT3 signaling in
    • Authors: Kuei-Yang Hsiao; Ning Chang, Jia-Ling Tsai, Shih-Chieh Lin, Shaw-Jenq Tsai, Meng-Hsing Wu
      Abstract: ProblemHow does hypoxia-mediated downregulation of dual-specificity phosphatase-2 (DUSP2) promote the development of endometriotic lesions'Method of studyThe levels of IL-6 and DUSP2 were assessed in eutopic stromal cells with DUSP2 knockdown or hypoxia treatment. Bromodeoxyuridine (BrdU) incorporation was applied for evaluating cell proliferation. The protein levels of DUSP2, cleaved caspase-3, phosphorylated STAT3, and STAT3 were analyzed using immunoblot.ResultsThe genomewide analysis of cells with DUSP2 overexpression indicated IL-6 regulates multiple pathways related to inflammation, proliferation, and apoptosis. DUSP2 overexpression significantly suppressed IL-6 expression, while DUSP2 knockdown promoted IL-6 expression. The hypoxia-treated eutopic stromal cells expressed higher levels of IL-6, recapitulating the elevated levels of IL-6 in ectopic stromal cells. The treatment with IL-6 elicited the phosphorylation of STAT3, mimicking the elevated levels of phosphorylated STAT3 in the ectopic stromal cells. The IL-6-treated eutopic stromal cells showed more BrdU incorporation and less cleaved caspase-3, which can be reversed by STAT3 inhibitor.ConclusionHypoxia-induced IL-6 production in endometriotic lesions is mediated via downregulation of DUSP2, which causes aberrant activation of STAT3 signaling pathway and helps the endometriotic cells survive under the ectopic environment.
      PubDate: 2017-04-25T05:50:46.935166-05:
      DOI: 10.1111/aji.12690
  • Endometrial immune markers are potential predictors of normal fertility
           and pregnancy after in vitro fertilization
    • Authors: Louise Kofod; Anette Lindhard, Michael Bzorek, Jens Ole Eriksen, Lise Grupe Larsen, Thomas Vauvert F. Hviid
      Abstract: ProblemElucidating immune mechanisms in the endometrium, which lead to the success of implantation and pregnancy, is important in reproductive medicine. Studies of immune cell abundance have shown conflicting results, and the expression and importance of HLA class Ib proteins in pre-implantation endometrium have not yet been investigated.Method of studyThe study population consisted of four subgroups: a hydrosalpinx, a salpingectomy, an unexplained infertility, and a fertile control group. Endometrial samples were collected during the implantation window. Immune markers (CD56+ and CD16+ cells, FoxP3+ Tregs, HLA-G, HLA-F) were quantified in the samples. The outcome of the subsequent IVF treatment was recorded.ResultsIncreased CD56+ uNK cells and high HLA-G expression served as predictor for successful pregnancy outcome. HLA-F expression was positively correlated with uNK cells, being indirectly predictive for achieving pregnancy.ConclusionEndometrial uNK cell abundance in the pre-implantation endometrium seems to be important for normal fertility and pregnancy success, and they may be used as clinical markers to predict implantation success in IVF.
      PubDate: 2017-04-25T05:50:15.139636-05:
      DOI: 10.1111/aji.12684
  • Soy isoflavones enhance β-defensin synthesis and secretion in endometrial
           epithelial cells with exposure to TLR3 agonist polyinosinic-polycytidylic
    • Authors: Yotesawee Srisomboon; Sutthasinee Poonyachoti, Chatsri Deachapunya
      Abstract: Problemβ-defensins are important innate chemical barriers that protect the endometrium from pathogen invasion. The effects of soy isoflavones, genistein and daidzein, on the expression and secretion of porcine β-defensins (PBD) in endometrial epithelial cells were investigated under normal or poly I:C-stimulated conditions.Method of studyPrimary cultured porcine endometrial epithelial (PE) cells were pretreated with genistein or daidzein followed by poly I:C inoculation. During treatment, the culture media were analyzed for PBD 1-4 secretion by ELISA and the total RNA for PBD gene expression by quantitative RT-PCR.ResultsPorcine endometrial epithelial cells constitutively expressed PBD 1-4 and secreted PBD-1, PBD-2, and PBD-4. Genistein and daidzein enhanced PBD-2 expression and PBD-2 and PBD-3 secretion. These compounds also potentiated PBD-2 and PBD-3 expression and secretion which were upregulated by poly I:C.ConclusionSoy isoflavones, genistein and daidzein, could be potentially used for promoting the innate host defense of endometrium against infection.
      PubDate: 2017-04-21T00:15:51.095928-05:
      DOI: 10.1111/aji.12694
  • Leukocyte counts and lymphocyte subsets in relation to pregnancy and HIV
           infection in Malawian women
    • Authors: Wilson L. Mandala; Esther N. Gondwe, Malcolm E. Molyneux, Jenny M. MacLennan, Calman A. MacLennan
      Abstract: ProblemWe investigated leukocyte and lymphocyte subsets in HIV-infected or HIV-uninfected, pregnant or non-pregnant Malawian women to explore whether HIV infection and pregnancy may act synergistically to impair cellular immunity.Method of studyWe recruited 54 pregnant and 48 non-pregnant HIV-uninfected women and 24 pregnant and 20 non-pregnant HIV-infected Malawian women. We compared peripheral blood leukocyte and lymphocyte subsets between women in the four groups.ResultsParturient HIV-infected and HIV-uninfected women had more neutrophils (each P
      PubDate: 2017-04-06T01:35:13.796787-05:
      DOI: 10.1111/aji.12678
  • Assessment of the immunogenicity of gonadotrophins during controlled
           ovarian stimulation
    • Authors: Carles Morte; Carles Celma, Christian De Geyter, Janos Urbancsek, Buenaventura Coroleu Lletget, Barbara Cometti
      Abstract: ProblemGonadotrophin hormones are used for the controlled ovarian stimulation (COS) as part of the in vitro fertilization techniques. Therapeutic proteins have the potential to induce an unwanted immune response.Method of studyThe presence of anti-FSH, anti-LH and anti-hCG antibodies were determined in patients from two different clinical trials after the repeated administration of hMG or FSH.ResultsIn the first study, 27 subjects were screening for the presence of anti-FSH antibodies. From the 27 patients, only one patient showed the presence of low levels of antibodies. In a second study, 25 patients were screened for the presence of anti-FSH, anti-LH and anti-hCG antibodies. At the end of the study, no patients showed the presence of antibodies.ConclusionThe results of this study suggest that repeated treatment cycles with FSH or hMG in patients undergoing COS for in vitro fertilization can be safely and effectively applied without concerns for immunogenicity.
      PubDate: 2017-04-05T04:46:26.360789-05:
      DOI: 10.1111/aji.12675
  • Relevance of Wnt10b and activation of β-catenin/GCMa/syncytin-1
           pathway in BeWo cell fusion
    • Authors: Sudha Saryu Malhotra; Priyanka Banerjee, Piyush Chaudhary, Rahul Pal, Satish Kumar Gupta
      Abstract: ProblemTo study the involvement of specific Wnt(s) ligand during trophoblastic BeWo cell differentiation.Method of studyBeWo cells on treatment with forskolin/human chorionic gonadotropin (hCG) were studied for cell fusion by desmoplakin I+II staining and/or hCG secretion by ELISA. Levels of Wnt10b/β-catenin/glial cell missing a (GCMa)/syncytin-1 were studied by qPCR/Western blotting in forskolin-/hCG-treated control siRNA and Wnt10b silenced BeWo cells.ResultsBeWo cells on treatment with hCG (5 IU/mL) led to a 94-fold increase in Wnt10b transcript. Wnt10b silencing showed significant decrease in forskolin-/hCG-mediated BeWo cell fusion and/or hCG secretion. It led to down-regulation of β-catenin (nuclear and cytoplasmic), GCMa and syncytin-1 expression. Treatment of BeWo cells with H89, protein kinase A (PKA) signaling inhibitor, significantly reduced forskolin-/hCG-induced Wnt10b, β-catenin, and syncytin-1 expression, which also resulted in reduced cell fusion.ConclusionWnt10b is involved in forskolin/hCG-mediated BeWo cell fusion via β-catenin/GCMa/syncytin pathway, which may also involve activation of PKA.
      PubDate: 2017-03-30T06:20:33.583807-05:
      DOI: 10.1111/aji.12676
  • Do Dose-related Mechanisms Exist for the Angiogenic Behaviours of Heparin
    • Authors: Celal Yavuz; Oğuz Karahan
      PubDate: 2012-06-22T05:27:17.053624-05:
      DOI: 10.1111/j.1600-0897.2012.1166.x
  • The myxovirus-resistance protein, MX1, is a component of exosomes secreted
           by uterine epithelial cells
    • Authors: Karen Racicot; Anthony Schmitt, Troy Ott
      Abstract: ProblemDairy cattle suffer from high percentages of early embryonic loss, and therefore, it is critical to study the function of the uterus at this time. We hypothesize that the antiviral protein, myxovirus resistance (MX)1, regulates secretion in uterine glandular cells during early pregnancy.Method of StudyUterine epithelial cells were used to study uterine function, in vitro. Sucrose gradients, Western blotting, and transmission electron microscopy were used to isolate and identify exosomes. Immunofluorescence and ceramide inhibitors were used for the characterization of exosomes.ResultsMyxovirus resistance1 was associated with exosomes and protected from proteases, indicating it was inside exosomes. MX1 partially colocalized with exosomal protein CD63, and a ceramide inhibitor reduced numbers of MX1-associated exosomes.ConclusionThis study is the first to characterize MX1-associated exosomes, and we postulate that MX1 regulates secretion in epithelial cells by playing a role in exosome formation or trafficking.
      PubDate: 2012-02-20T02:48:38.465091-05:
      DOI: 10.1111/j.1600-0897.2012.01109.
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