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Publisher: John Wiley and Sons   (Total: 1576 journals)

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Showing 1 - 200 of 1576 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: 58, 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: 51, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 139, 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: 2)
Addiction     Hybrid Journal   (Followers: 33, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 12, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 24, 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: 250, 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: 44, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 29, 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: 128, 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: 91, 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: 31, 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: 15, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 3, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 5, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 36, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 250, 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: 16, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 120, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 11, 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: 161)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 209, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 35, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, 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: 8, 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: 44, 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: 12)
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: 16, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 14)
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: 93, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 45, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 6, 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: 67, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 136, 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: 34, 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: 14, 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: 218, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 51, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 28, 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: 14)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 315, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 7, 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: 3, 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: 13, 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: 12, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 10, 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: 43, 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: 6, 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: 23, 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: 13, 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: 392, 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: 66, 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: 31, 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: 4, 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: 23, 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: 15, 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: 37, 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: 133, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 13, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 18, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 10, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 34, 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: 219, 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  [1576 journals]
  • 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
  • Issue Information
    • PubDate: 2017-07-20T05:53:12.118846-05:
      DOI: 10.1111/aji.12573
  • Reproductive immunology in Asia: An international collaboration
    • Authors: Gil Mor
      Abstract: Percentage of global access to articles published in the AJRI by investigators in the USA and China.
      PubDate: 2017-07-20T05:53:10.913628-05:
      DOI: 10.1111/aji.12729
  • Introduction to the Chinese society for reproductive immunology
    • Authors: Da-Jin Li
      PubDate: 2017-07-20T05:53:08.571705-05:
      DOI: 10.1111/aji.12718
  • 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
  • The role of γδ-T cells during human pregnancy
    • Authors: Chunyu Huang; Yong Zeng, Wenwei Tu
      Abstract: Pregnancy is an evolutionarily important and mysterious process. The placenta, as the nutrient and gas exchange organ, plays an essential role during this process. In addition, the interaction between trophoblast and maternal immune cells at the maternal–fetal interface is also associated with successful pregnancy. Human leukocyte antigen (HLA) molecules on trophoblast cells are involved in protecting the fetus from maternal rejection. Trophoblast cells comprise three subpopulations, including syncytiotrophoblast cells, cytotrophoblast cells, and extravillous trophoblast cells, and these cells express different HLA molecules. Syncytiotrophoblast and extravillous trophoblast cells encounter maternal immune cells from different sources, such as blood or decidua. The increased γδ-T cells during human normal pregnancy indicate that these cells may play a role in this process. In peripheral blood, Vγ9Vδ2-T cells display cytotoxicity through the recognition of phosphoantigens derived from pathogens. However, HLA-E molecules protect the trophoblast cells from the cytotoxicity of Vγ9Vδ2-T cells through binding to the inhibitory receptor, CD94/NKG2A. In decidua, the main Vδ1-T cells maintain the pregnancy through the secretion of cytokines. In addition, the imbalance between Vγ9Vδ2-T and Vδ1-T cells, and the abnormal expression of the receptors on γδ-T cells were observed in adverse pregnancy.
      PubDate: 2017-06-27T00:57:44.328399-05:
      DOI: 10.1111/aji.12713
  • 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
  • The regulations and role of circadian clock and melatonin in uterine
           receptivity and pregnancy—An immunological perspective
    • Authors: Gene Chi Wai Man; Tao Zhang, Xiaoyan Chen, Jianzhang Wang, Fangrong Wu, Yingyu Liu, Chi Chiu Wang, Ying Cheong, Tin Chiu Li
      Abstract: During normal pregnancy, the mechanism by which the fetus escapes immunological rejection by the maternal womb remains elusive. Given the biological complexities, the immunological mechanism is unlikely to be simply an allograft response in acceptance or rejection of the early pregnancy. Circadian clock responsible for the mammalian circadian rhythm is an endogenously generated rhythm associated with almost all physiological processes including reproduction. There is now growing evidence to suggest that the circadian clocks are intricately linked to the immune system and pregnancy. When perturbed, the role of immune cells can be affected on maintaining the enriched vascular system needed for placentation. This alteration can be triggered by the irregular production of maternal and placental melatonin. Hence, the role of circadian rhythm modulators such as melatonin offers intriguing opportunities for therapy. In this review, we evaluate the complex interaction between the circadian clock and melatonin within the immune system and their roles in the circadian regulation and maintenance of normal pregnancy.
      PubDate: 2017-06-06T06:45:47.488284-05:
      DOI: 10.1111/aji.12715
  • 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
  • The roles of the PD-1/PD-L1 pathway at immunologically privileged sites
    • Authors: Li-Ling Wang; Zhi-Hui Li, Xiao-Hui Hu, Kahinho P. Muyayalo, Yong-Hong Zhang, Ai-Hua Liao
      Abstract: The PD-1/PD-L1 pathway plays a vital role in the maintenance of peripheral tolerance, promoting the development and function of regulatory T cells, and maintaining the quiescence of autoreactive T cells. Abnormalities in this inhibitory pathway are involved in the pathogenesis of some disorders such as tumours, autoimmune diseases, pregnancy complications, and transplantation rejection. Immune privilege represents a special immunological condition, where foreign antigens can be tolerated and do not elicit an immune response. The anterior chamber of the eye, central nervous system, testis, pregnant uterus, and hair follicles are all regarded as immune-privileged sites in humans. Numerous studies show that the PD-1/PD-L1 pathway contributes to the maintenance of the immune-privileged microenvironment. In this review, we will mainly focus on the roles of the PD-1/PD-L1 pathway in the anterior chamber of the eye, brain and testis, as well as further investigations in testis.
      PubDate: 2017-06-06T06:05:23.367107-05:
      DOI: 10.1111/aji.12710
  • Immunological function of vitamin D during human pregnancy
    • Authors: Jin-Lu Ji; Kahinho P. Muyayalo, Yong-Hong Zhang, Xiao-Hui Hu, Ai-Hua Liao
      Abstract: The well-established classic role of vitamin D is implicated in the regulation of the balance between calcium and phosphorus. Furthermore, vitamin D is also involved in many non-classic physiological processes, mainly including the regulation of cell proliferation, differentiation, apoptosis and immune function, participation in the inflammatory response and maintenance of genome stability function. During pregnancy, vitamin D receptor and its metabolic enzymes are expressed at the placenta and decidua, indicating the potential role in the mechanism of immunomodulation at the maternal-fetal interface. The insufficiency or deficiency of vitamin D may affect the mother directly and is related to specific pregnancy outcomes, such as preeclampsia, gestational diabetes, and recurrent miscarriage. This article reviews the effects of vitamin D on immune regulation during pregnancy.
      PubDate: 2017-06-06T05:50:21.082881-05:
      DOI: 10.1111/aji.12716
  • 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
  • Functional properties of peripheral CD8+ T cells in patients with
           repeated implantation failure
    • Authors: Biao Yin; Yong Zeng, Tonghua Wu, Shuyi Yu, Jian Xu, Su Liu, Lianghui Diao, Zhenfu Zhao, Desheng Liang, Yuye Li
      Abstract: CD8+ T cells are the main candidates to recognize and respond to fetal HLA-C at the fetal-maternal interface, but data on the amount of peripheral CD8+ T cells and their functions during the window of implantation in recurrent implantation failure (RIF) patients are limited. Peripheral blood was obtained from 56 women with RIF and 16 fertile women in the mid-luteal phase of the menstrual cycle, and the CD8+ T cells were determined by FACS analysis. No statistical differences in the proportion of peripheral CD8+ T cells were observed among the women with RIF and the control group. However, the levels of IFN-γ+ and TNF-α+ CD8+ T cells in the RIF group were significantly higher than those in the control group. The cytolytic activity and regulatory proportion of CD8+ T cells in RIF were similar to that in the control group. Our data indicated that the elevated expression levels of IFN-γ and TNF-α in peripheral CD8+ T cells may contribute to an impaired immune tolerance in women with RIF.
      PubDate: 2017-05-15T22:55:26.512608-05:
      DOI: 10.1111/aji.12704
  • Efficacy of intrauterine perfusion of granulocyte colony-stimulating
           factor (G-CSF) for Infertile women with thin endometrium: A systematic
           review and meta-analysis
    • Authors: Yiran Xie; Tao Zhang, Zhengping Tian, Jiamiao Zhang, Wanxue Wang, Hong Zhang, Yong Zeng, Jianping Ou, Yihua Yang
      Abstract: This meta-analysis aimed to explore the efficiency of intrauterine perfusion of granulocyte colony-stimulating factor (G-CSF) on infertile women with thin endometrium. Following PRISMA protocol, we conducted a comprehensive search of academic literatures on various databases including PubMed, EMbase, and Cochrane Library. Studies published in English before July 1, 2016 were included for primary screening. Data on the thickness of endometrium, cycle cancelation rate,clinical pregnancy rate, and embryo implantation rate were extracted and analyzed, respectively. Eleven eligible studies involving 683 patients were included in this meta-analysis. Compared with control group, G-CSF perfusion could significantly improve endometrial thickness (mean difference [MD]=1.79, 95% confidence interval (CI): 0.92-2.67), clinical pregnancy rate (risk ratio [RR]=2.52, 95% CI: 1.39-4.55), and embryo implantation rate (RR=2.35, 95% CI: 1.20-4.60), while it could decrease cycle cancelation rate (RR=0.38, 95% CI: 0.25-0.58). Funnel plots revealed that there was no evidence of publication bias. The current data indicate that intrauterine perfusion of G-CSF can improve endometrial thickness, clinical pregnancy rate, and embryo implantation rate, but decrease the cycle cancelation rate in women with thin endometrium.
      PubDate: 2017-05-12T06:00:28.904362-05:
      DOI: 10.1111/aji.12701
  • 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
  • Physiological and pathological angiogenesis in endometrium at the time of
           embryo implantation
    • Authors: Xiaoyan Chen; Gene Chi Wai Man, Yingyu Liu, Fangrong Wu, Jin Huang, Tin Chiu Li, Chi Chiu Wang
      Abstract: Embryo establishes contact with the endometrium during implantation. Proper endometrial vascular development and maintenance at the time of embryo implantation is crucial for successful pregnancy. Vascular development at the maternal-embryo interface can be regulated by various cell types, of which uterine natural killer (uNK) cells play an important role. Abnormal angiogenesis and uNK cell number/function may lead to reproductive failure, particularly in women with recurrent miscarriage (RM) and women with recurrent implantation failure (RIF) after IVF-ET treatment, which are the important clinical hurdles in reproductive medicine to overcome. In this review, we aim to discuss the current knowledge of physiological angiogenic processes and the pathological angiogenesis at the time of implantation, as well as the possible mechanism and potential treatment.
      PubDate: 2017-05-03T03:55:24.039206-05:
      DOI: 10.1111/aji.12693
  • 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
  • Detection of invariant natural killer T cells in ejaculates from infertile
           patients with chronic inflammation of genital tract
    • Authors: Yong-Gang Duan; Shujian Chen, Gerhard Haidl, Jean-Pierre Allam
      Abstract: Chronic inflammation of genital tract is thought to play a major role in male fertility disorder. Natural killer (NK) T cells are a heterogeneous group of T cells that share properties of both T cells and NK cells which display immunoregulatory properties. However, little is known regarding the presence and function of NK T cells in ejaculates from patients with chronic inflammation of genital tract. Invariant NK T (iNK T) cells were detected by invariant (Vα24-JαQ) TCR chain in ejaculates from patients suffering from chronic inflammation of genital tract (CIGT) using flow cytometry and immunofluorescence of double staining (n=40). Inflammatory cytokines interleukin (IL)-6, IL-17, and IFN-γ were detected in cell-free seminal plasma using an enzyme-linked immunosorbent assay (ELISA). The correlation between the percentage of iNK T cells and spermatozoa count, motility, vitality, seminal IL-6, IL-17, and IFN-γ was investigated. Significant percentages of iNK T cells above 10% were detected in 50% (CIGT-NKT+ group). A negative correlation was detected between the percentage of iNK T cells and spermatozoa count (r=−.5957, P=.0056), motility (r=−.6163, P=.0038), and vitality (r=−.8032, P=.0019) in CIGT-NKT+ group (n=20). Interestingly, a significant correlation of iNK T cells to seminal IL-6 (r=.7083, P=.0005), IFN-γ (r=.9578, P
      PubDate: 2017-04-03T03:45:38.026353-05:
      DOI: 10.1111/aji.12671
  • In appreciation
    • Authors: Sung Ki Lee
      PubDate: 2017-03-30T06:25:24.724926-05:
      DOI: 10.1111/aji.12680
  • 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
  • Expression of TWIST in the first-trimester trophoblast and decidual tissue
           of women with recurrent pregnancy losses
    • Authors: Jin Hee Ahn; Hye Ran Park, Chan-Woo Park, Dong-Wook Park, Joanne Kwak-Kim
      Abstract: ProblemIn this study, we aim to investigate if the expression of TWIST in the first-trimester placenta and decidua has any association with spontaneous abortion (SAB) and recurrent pregnancy losses (RPL).MethodsExpression of TWIST was measured in the first-trimester trophoblast and decidual tissues using RT-PCR and immunohistochemistry. Women with a pregnancy loss comprised the study group (AB group) including women with two or more recurrent pregnancy loses (RPL group), and women with a spontaneous abortion who had no history of previous pregnancy losses (SAB group). Controls were women with elective abortion of normal pregnancy (NP group).ResultsIn in-vitro culture study of endometrial cells, expression of TWIST was detected with the induction of decidualization. In syncytiotrophoblast, expression of TWIST in NP group was significantly higher than that of AB group. RPL group had no expression of TWIST, both in the nucleus and cytoplasm of syncytiotrophoblast. In decidual tissue, majority of TWIST was expressed on the decidual stromal cells. NP group showed significantly higher expression of TWIST in cytoplasm and nucleus as compared with those of SAB group.ConclusionThis suggests that TWIST may have a functional role in decidualization of endometrial cells and syncytialization of cytotrophoblast cells.
      PubDate: 2017-03-24T01:25:42.408728-05:
      DOI: 10.1111/aji.12670
  • Activation of NOD-1/JNK/IL-8 signal axis in decidual stromal cells
           facilitates trophoblast invasion
    • Authors: Byung Jun Ryu; Jae Won Han, Ryang Hee Kim, Sohyun Yun, Tae Hyun Kim, Sung Eun Hur, Chul Jung Kim, Sung Ki Lee
      Abstract: Decidual stromal cells (DSCs) are known to regulate trophoblast invasion via unveiled mechanism yet. And nucleotide-binding oligomerization domain-containing protein 1 (NOD1) may influence on this DSC-trophoblast interaction. We investigated the mechanism underlying the DSC-mediated regulation of trophoblast invasion and the effect of NOD1 on their cross talk. Using human primary DSCs, BeWo cell invasion was measured. Cytokine secretion and MAP kinase signaling were examined in DSCs following treatment with NOD1 agonist, Tri-DAP. DSCs secreted IL-8 and increased trophoblast invasion. Tri-DAP further increased IL-8 secretion from DSCs via JNK pathway and facilitated both MMP-2 production and trophoblast invasion compared with control. Upon cotreatment of IL-8 and anti-IL-8 antibody to BeWo cells, the number of invading trophoblasts and MMP-2 production decreased significantly. These results suggest that IL-8 from DSCs may play a role to increase the invasiveness of trophoblast cells into the decidua via NOD1/JNK pathway.
      PubDate: 2017-03-22T05:00:55.318823-05:
      DOI: 10.1111/aji.12672
  • The transdifferentiation of regulatory T and Th17 cells in
           autoimmune/inflammatory diseases and its potential implications in
           pregnancy complications
    • Authors: Zhao-Zhao Liu; Guo-Qiang Sun, Xiao-Hui Hu, Joanne Kwak-Kim, Ai-Hua Liao
      Abstract: In the past decades, studies have shown that a balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells plays a major role in autoimmune/inflammatory diseases as well as pregnancy complications. Decreased number and function of Tregs, and increased number of Th17 cells which often have an opposed effect of Tregs, are associated with these conditions. Recently, the plasticity of Tregs and Th17 cells has been reported to be involved in the pathogenesis of autoimmune/inflammatory diseases. Hence, we summarize the current knowledge of Tregs and Th17 cells plasticity with an emphasis on their reciprocal transdifferentiation in autoimmune/inflammatory diseases. Moreover, the regulators of the Tregs-to-Th17 cells transdifferentiation are discussed as well. Finally, by reviewing the immuno-inflammatory status of pregnancy complications, such as preeclampsia and unexplained recurrent pregnancy losses, a possibility of Tregs-to-Th17 cells transdifferentiation as an underlying immune-pathology of these conditions is discussed.
      PubDate: 2017-03-02T02:35:24.023296-05:
      DOI: 10.1111/aji.12657
  • Trophoblasts regulate natural killer cells via control of interleukin-15
           receptor signaling
    • Authors: Seo Y. Park; Sohyun Yun, Byung J. Ryu, Ae R. Han, Sung K. Lee
      Abstract: ProblemTrophoblasts are known to decrease natural killer (NK) cell cytotoxicity. However, little is known about the interaction between trophoblasts and NK cells during pregnancy. Interleukin-15 (IL-15) is essential for priming NK cells and maximizing their effector functions. We investigated whether trophoblasts regulate NK cell activation via IL-15/IL-2 receptor and its signaling pathways.Method of studyNatural killer-92 cells were primed with human first-trimester trophoblast cells (Sw.71) conditioned medium (CM) and co-cultured with K562 cells. Flow cytometry, Western blot analysis, and real-time PCR were performed to assess NK cell cytotoxicity, IL-15/IL-2 receptor expression, phosphorylation of STAT5 and MAPKs, and mRNA expression of IL-15-related genes.ResultsNatural killer-92 cells incubated with Sw.71 CM showed reduced cytotoxicity and IL-15-mediated proliferation, and expression of IL-15/IL-2 receptor subunits. STAT5 phosphorylation, EOMES and T-bet mRNA expressions, and ERK/JNK pathways of NK 92 cells were suppressed by Sw.71 CM. Productions of perforin, granzyme B, and IFN-γ were also downregulated.ConclusionTrophoblasts regulate human NK cell functions via suppression of IL-15/IL-2 receptor expression, transcription factors, and ERK/JNK pathways.
      PubDate: 2017-03-02T02:20:28.11402-05:0
      DOI: 10.1111/aji.12628
  • The CCL17-CCR4 axis between endometrial stromal cells and macrophages
           contributes to the high levels of IL-6 in ectopic milieu
    • Authors: Wen-Jie Zhou; Xin-Xin Hou, Xiao-Qiu Wang, Da-Jin Li
      Abstract: Endometriosis is a chronic inflammatory disease characterized by the elevation of proinflammatory cytokines, such as IL-6, in the peritoneal fluid. However, the precise mechanism of the highly elevated IL-6 levels in ectopic milieu remains unclear. The aim of this study was to investigate whether the cross talk between endometrial stromal cells (ESCs) and macrophages contributes to the elevated IL-6 production. Samples of endometrium and ectopic tissues were obtained from patients with or without endometriosis. The peripheral blood samples were collected from healthy volunteers. Enzyme-linked immunosorbent assay (ELISA) was for IL-6 levels in peritoneal fluid and cell culture supernatant. In-Cell Western assay was used for protein expression of CCL17 and phosphorylation levels of ERK, JNK, and P38. Immunohistochemistry was performed on normal, eutopic endometrium and ectopic tissues to analyze CCL17 expression. Flow cytometry was applied to detect the expression of CCR4, IL-6, and the phosphorylation levels of NF-κB. Patients with endometriosis have higher levels of IL-6 in peritoneal fluid compared to the control. The co-culture of ESCs and macrophages produce more IL-6 than cultured alone, respectively. The eutopic endometrium had significantly higher expression of CCL17 compared to normal endometrium, and the ectopic tissues had the highest expression. IL-6 induced CCL17 secretion in ESCs via activating JNK signaling pathway, CCL17 upregulated the expression of its receptor CCR4 on macrophages. Furthermore, CCL17-CCR4 axis subsequently led to excessive IL-6 production in macrophages by activating NF-κB. These findings suggest that the cross talk between ESCs and macrophages promotes the expression of CCL17 in ESCs and CCR4 on macrophages, which contributes to the high levels of IL-6 in ectopic milieu.
      PubDate: 2017-02-27T05:20:39.647468-05:
      DOI: 10.1111/aji.12644
  • Aberrant expressions of endometrial Id3 and CTLA-4 are associated with
           unexplained repeated implantation failure and recurrent miscarriage
    • Authors: Jin-Li Ding; Liang-Hui Diao, Tai-Lang Yin, Chun-Yu Huang, Biao Yin, Cong Chen, Yi Zhang, Jie Li, Yan-Xiang Cheng, Yong Zeng, Jing Yang
      Abstract: Inhibitor of DNA-binding protein 3 (Id3) is required for tumor angiogenesis and regulatory T-cell generation. However, the involvement of Id3 in unexplained repeated implantation failure (RIF) and recurrent miscarriage (RM) remains poorly understood. Immunohistochemistry was used to identify Id3, CD34, CTLA-4, and FOXP3 in the endometrium taken from the women with RIF (n=16), RM (n=16) and matched controls (n=8). The images were acquired and analyzed by the Vectra® automated quantitative pathology imaging system. Percentage of Id3+ cells was significantly higher in the endometrium of women with RIF and RM compared with controls. The numbers of Id3+ and CD34+ vessels in the endometrium were positively correlated in control but not in RIF or RM. Percentages of CTLA-4+ cells, but not FOXP3+ cells, were significantly increased in the endometrium of RIF and RM women than those in controls. We found aberrant expressions of endometrial Id3 and CTLA-4 in peri-implantation endometrium of women with RIF and RM, suggesting the negative roles of these angiogenesis and immune tolerance markers involving in regulating endometrium receptivity.
      PubDate: 2017-02-21T23:45:35.897009-05:
      DOI: 10.1111/aji.12632
  • Microbiome, autoimmunity, allergy, and helminth infection: The importance
           of the pregnancy period
    • Authors: Xian Chen; Su Liu, Qiao Tan, Yehuda Shoenfeld, Yong Zeng
      Abstract: Pregnancy is a special physical period in reproductive age women, which has a beneficial influence on the course of certain autoimmune diseases. It has been recently suggested that the microbiome undergoes profound changes during pregnancy that are associated with host physiological and immunological adaptations. The maternal microbiome remodeling during pregnancy is an active response of the mother, possibly to alter immune system status and to facilitate metabolic and immunological adaptations, which are needed for a successful pregnancy. In this review, we attempt to discuss (i) the role of maternal microbiome in pregnancy outcomes known to adversely influence neonatal and infant health, including preterm birth, cardiometabolic complications of pregnancy, and gestational weight gain; (ii) the association of microbiome with autoimmunity, allergy diseases, and asthma during pregnancy; and (iii) the impact of helminth infection during pregnancy.
      PubDate: 2017-02-21T23:40:20.893477-05:
      DOI: 10.1111/aji.12654
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