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Publisher: John Wiley and Sons   (Total: 1589 journals)

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Showing 1 - 200 of 1589 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: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 48, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 53, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 168, 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: 6, 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: 37, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 5)
Addiction     Hybrid Journal   (Followers: 36, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 14, 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: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 295, 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: 7, 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: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 11)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, 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: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 152, 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: 93, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 35, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 13, 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: 290, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 16, 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: 18, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 138, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 9, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 20)
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: 179)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 229, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, 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: 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: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, 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: 25, 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: 50, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, 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: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 209, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 50, 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: 32, 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: 29, 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: 26, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 13, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 274, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 54, 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: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 326, 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   (Followers: 1, SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, 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: 3, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 15, 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: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, 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: 47, 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: 6, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, 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: 15, 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: 419, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 23, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, 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: 11, 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: 10, 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: 5, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, 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: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 152, 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: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, 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: 7, 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: 247, 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  [1589 journals]
  • Application of computer-aided sperm analysis (CASA) for detecting
           sperm-immobilizing antibody
    • Authors: Yu Wakimoto; Atsushi Fukui, Teruhito Kojima, Akiko Hasegawa, Minoru Shigeta, Hiroaki Shibahara
      Abstract: ProblemSince the 1970s, anti-sperm antibodies have been studied as a pathogenic factor contributing to infertility. The complement-dependent sperm-immobilization test (SIT) and quantitative SIT have been used as effective tools for detecting anti-sperm antibodies in clinical settings. These tests have been carried out traditionally by manually counting the number of motile sperm through eye estimation.Method of studyIn this study, we developed a novel method using computer-aided sperm analysis. The results were compared with those obtained by the traditional method.ResultsThe results were identical and 25 of 78 samples tested were positive and 53 samples were negative for sperm-immobilizing (SI) antibodies based on both methods. For SI-positive samples, the values of SI50 obtained using the two methods correlated closely with high co-efficiency.ConclusionUsing the novel method, manually counting the number of motile spermatozoa becomes unnecessary. The novel method presented here will increase the objectivity and convenience of using the SIT as a clinical indicator.
      PubDate: 2018-01-19T05:45:44.884433-05:
      DOI: 10.1111/aji.12814
  • Immune protective effects of chitooligosaccharides on mice genital tract
           infected by Chlamydia trachomatis
    • Authors: Li Qian; Linjun Chen
      Abstract: ProblemThe immune protective effects of chitooligosaccharides (COs) on mouse genital tract infected by Chlamydia trachomatis (Ct) were unknown.MethodsThe minimum effective/infective dose was obtained by establishing the murine model of the genital tract infected by Ct. The model mice were treated with different doses (0.1, 0.2, and 0.3 g/kg,) of COs and 0.9% saline, and the serum immunoglobulin G (IgG) antibody and interleukin (IL)-11 levels were then assayed. The healthy mice were used as the control. After 1 week of immunity, a double-effective/infective dose of Ct was used to attack the genital tract. After 10 days of experiment, the mice were killed, their spleen and thymus indexes were determined, and the pathological changes in their genital tract were evaluated.ResultsTreatment with COs increased the serum IgG antibody, IL-11 levels, and spleen and thymus indexes but decreased the positive infection rate and inclusion body formation with Ct.ConclusionCOs could induce immune protection on the Ct-infected mouse genital tract and might be used as an alternative drug for the treatment of genital tract infected with Ct.
      PubDate: 2018-01-18T09:20:21.715338-05:
      DOI: 10.1111/aji.12815
  • Soluble CD14 levels in plasma and breastmilk of Malawian HIV+ women: Lack
           of association with morbidity and mortality in their exposed infants
    • Authors: Silvia Baroncelli; Clementina M. Galluzzo, Giuseppe Liotta, Mauro Andreotti, Fausto Ciccacci, Sandro Mancinelli, Victor T. Tolno, Jane Gondwe, Roberta Amici, Maria C. Marazzi, Stefano Vella, Marina Giuliano, Leonardo Palombi, Lucia Palmisano
      Abstract: ProblemData on soluble CD14 (sCD14) during pregnancy and lactation are scarce. We assessed the levels of sCD14 in plasma and breastmilk of Malawian HIV-positive women and evaluated the possible association with morbidity and mortality in the HIV-exposed children.Method of studyOne hundred and forty-nine mother/child pairs were studied. Women received antiretroviral therapy from 26 weeks of gestation to at least 6 months of exclusive breastfeeding. sCD14 concentrations were determined using an enzyme-linked immunosorbent assay.ResultssCD14 levels measured at 26 weeks of pregnancy (median: 1418 ng/mL, IQR: 1086-1757) were inversely correlated to maternal CD4+ cell count (r = −.283, P = .001) and to neonatal birthweight (r = −.233, P = .008). At 6 months, sCD14 plasma levels were significantly higher compared to baseline (1993 ng/mL, IQR: 1482-2604, P 
      PubDate: 2018-01-11T07:16:04.036729-05:
      DOI: 10.1111/aji.12812
  • Impaired Treg and NK cells profile in overweight women with gestational
           diabetes mellitus
    • Authors: Thalita Frutuoso Lobo; Camila de Moraes Borges, Rosiane Mattar, Caio Perez Gomes, Ana Geisa Santos Angelo, Karen Priscilla Tezotto Pendeloski, Silvia Daher
      Abstract: ProblemMaternal obesity is frequently associated with gestational diabetes mellitus (GDM), and immunological mechanisms seem to be involved in the physiopathology of these conditions. The aim of this study was to characterize the profile of immune cells in peripheral blood of overweight women with GDM.Method of StudyThis case-control study included 27 glucose-tolerant (controls) and 31 GDM overweight pregnant women. Flow cytometry was used to assess the number of regulatory T cells (Treg) and natural killer (NK) cells in the peripheral blood. In addition, the expression of IL-10, TGF-B, and TNF-A in Treg and expression of IFN-G, TNF-A, granzyme, and perforin in NK cells were analyzed.ResultsGDM patients had significantly lower frequency of TCD4+CD25bright and TCD4+CD25+FOXP3high cells, higher production of TNF-A by Treg cells and higher percentage of NKCD16+56dim cells than the controls.ConclusionThe association between obesity and GDM is a condition where it is observed impaired Treg and NK cells profile, findings that seem to be related with the development of IR and inflammation.
      PubDate: 2018-01-05T10:05:26.94366-05:0
      DOI: 10.1111/aji.12810
  • Effects of intrauterine perfusion of human chorionic gonadotropin in women
           with different implantation failure numbers
    • Authors: Pinxiu Huang; Lihong Wei, Xinlin Li, Aiping Qin
      Abstract: ProblemThe aim of this research was to investigate the effects of the intrauterine perfusion of hCG before a frozen-thawed embryo transfer (FET) in women with different implantation failure numbers.Method of StudyThis was a retrospective analysis of patients undergoing FET who received an intrauterine injection hCG 1000 IU before embryo transfer. The groups included women with their first implantation failure (A group, n = 26), second implantation failure (B group, n = 122), and three or more failures (C group, n = 77). Corresponding control groups (no infusion) were also included. The pregnancy rates were compared among these groups.ResultsAfter intrauterine injection hCG, the biochemical pregnancy rates were 92.30%, 63.11%, 49.02%, and the clinical pregnancy rates were 76.92%, 54.91%, 48.05%, in the A, B, and C groups, respectively. The biochemical and clinical pregnancy rates were significantly higher in the A group than in the other groups (P 
      PubDate: 2017-12-30T02:15:22.970925-05:
      DOI: 10.1111/aji.12809
  • Cancer immunotherapy: A need for peripheral immunodynamic monitoring
    • Authors: Wenjun Wang; Xiaojun Xia, Sipei Wu, Minzhang Guo, Puyi Lie, Jianxing He
      Abstract: Immunotherapy has become an important approach for treating different tumours which has shown significant efficacy in numerous clinical trials, especially those using new checkpoint inhibitors and adoptive cell therapy, which have rapidly become widespread after being approved. However, analysis of peripheral immune biomarkers before and after immunotherapy and their relationship to clinical responses and disease prognosis have rarely been performed in clinical trials. In this review, we examine dynamic changes in the immune system before and after therapy by analyzing recent clinical trials of immunotherapy in patients with cancer that focused on checkpoint inhibitors and adoptive cell therapy. Our aim was to identify circulating biomarkers which can specifically predict clinical response and prognosis, as well as toxicities of immunotherapy. Through this approach, we hope to advance our understanding of the mechanisms of immunotherapy with the goal of developing individualized treatment for cancer patients.
      PubDate: 2017-12-30T01:00:38.795664-05:
      DOI: 10.1111/aji.12793
  • Localized cyclical variations in immunoproteins in the female genital
           tract and the implications on the design and assessment of mucosal
           infection and therapies
    • Authors: Julia Makinde; Clifford Jones, Angela Bartolf, Sengeziwe Sibeko, Susan Baden, Catherine Cosgrove, Robin J. Shattock
      Abstract: ProblemFluctuating hormones regulate reproductive processes in the female genital tract. Consequent changes in the local immunological environment are likely to affect cellular interaction with infectious agents and the assessment of therapies that target mucosal infections.Method of studyWe compared Softcup and Weck-Cel sampling protocols and assessed the changes in the concentrations of 39 soluble proteins with menstrual cycle progression in the mucosal and peripheral compartments.ResultsWe demonstrate that the mucosal immunological profile is distinct from serum with inflammatory and migratory signatures that are localized throughout the cycle. The analytes highlighted in the mucosal compartment were generally highest at the follicular phase with a tendency to fall as the cycle progressed through ovulation to the luteal phase.ConclusionOur results underscore the need to consider these localized cyclical differences in studies aimed at assessing the outcome of disease and the efficacy of mucosal vaccines and other therapies.The female mucosal secretome is distinct from serum with characteristic inflammatory and migratory signatures that reflect the local cyclical hormonal changes.
      PubDate: 2017-12-29T05:36:12.532589-05:
      DOI: 10.1111/aji.12801
  • Toll-like receptor variants and cervical Atopobium vaginae infection in
           women with pelvic inflammatory disease
    • Authors: Brandie D. Taylor; Patricia A. Totten, Sabina G. Astete, Michael J. Ferris, David H. Martin, Roberta B. Ness, Catherine L. Haggerty
      Abstract: ProblemToll-like (TLR) receptor genetic variants have been implicated in bacterial vaginosis (BV). We determined whether TLR variants are associated with fastidious BV-associated microbes that are linked with infertility following pelvic inflammatory disease (PID).Method of studySneathia spp., Atopobium vaginae, BVAB1, and Ureaplasma urealyticum were measured in 250 women from the PID Evaluation and Clinical Health (PEACH) study. Relative risk (RR) and 95% confidence intervals (CI) were calculated adjusting for chlamydia and gonorrhea. Principal component analysis was used to adjust for population stratification. A false discovery rate q-value of 0.05 was significant.ResultsTLR2-1733C>A (P = .003) and TLR2-616A>G (P = .004) were associated with cervical A. vaginae. TLR2-1733C>A and TLR6-438C>T were associated with A. vaginae detection in the endometrium, but this was not significant after adjustment for multiple comparisons (FDR q-value = 0.06).ConclusionHost gene variants in TLR2 signaling pathways were modestly associated with cervical A. vaginae in women with clinical PID.
      PubDate: 2017-12-29T05:31:30.00117-05:0
      DOI: 10.1111/aji.12804
  • Sludge reflects intra-amniotic inflammation with or without microorganisms
    • Authors: Noriko Yoneda; Satoshi Yoneda, Hideki Niimi, Masami Ito, Kaori Fukuta, Tomohiro Ueno, Mika Ito, Arihiro Shiozaki, Mika Kigawa, Isao Kitajima, Shigeru Saito
      Abstract: ProblemTo investigate whether amniotic fluid (AF) “sludge” in patients with preterm labor (PTL) with intact membranes is related to intra-amniotic infection or inflammation.Method of study105 PTL patients before 29 weeks’ gestation were enrolled. AF “sludge” was evaluated by transvaginal sonography. Microorganisms were identified in AF by our newly established PCR method using a eukaryote-made thermostable DNA polymerase.ResultsAF “sludge” was present in 18.1% (19/105) of patients. The results obtained in the AF “sludge” group vs the no “sludge” group were as follows: (i) a similar positive rate of microorganisms in AF by PCR, 31.6% (6/19) vs 38.4% (33/86); (ii) a higher level of AF interleukin-8, 15.2 (0.2-381.5) ng/mL vs 5.8 (0.1-413.7) ng/mL; P = .005); and (3) a higher frequency of histological chorioamnionitis, 52.6% (10/19) vs 23.3% (20/86); P = .010.ConclusionThe presence of AF “sludge” is related to intra-amniotic inflammation with or without microorganisms.
      PubDate: 2017-12-27T05:10:26.867352-05:
      DOI: 10.1111/aji.12807
  • Chorioamnionitis, IL-17A, and fetal origins of neurologic disease
    • Authors: Shelley M. Lawrence; James L. Wynn
      Abstract: The Centers for Disease Control and Prevention estimate that 1 in 323 infants have cerebral palsy. Highly correlated to intrauterine infection and inflammation, the incidence of cerebral palsy has remained constant over the last few decades despite significant advances in neonatal intensive care including improved ventilator techniques, surfactant therapy, maternal steroid administration, and use of intrapartum empiric antimicrobials. Recent advances in our understanding of immune responses to infection and inflammation have identified the cytokine IL-17A as a crucial component of early proinflammatory mediators that cause brain injury associated with neurologic impairment. Remarkably, maternal inflammatory responses to in utero inflammation and infection can also lead to potentially debilitating neurologic conditions in the offspring, which often become clinically apparent during childhood and/or early adulthood. This review details the role of IL-17A in fetal and maternal proinflammatory responses that lead to fetal brain injury and neurologic sequelae, including cerebral palsy. Recent findings regarding the role of maternal inflammatory responses in the development of childhood and adult neurologic conditions, such as autism, schizophrenia, and multiple sclerosis, will also be highlighted.
      PubDate: 2017-12-22T05:28:26.252529-05:
      DOI: 10.1111/aji.12803
  • Characterization of CD127− CD25++ Treg from human colostrum
    • Authors: Arturo Cérbulo-Vázquez; Graciela Hernández-Peláez, Lourdes A. Arriaga-Pizano, Paulina Bautista-Pérez, Jannett Romero-Venado, Julio C. Flores-González, Ricardo Figueroa-Damian, Diana Soriano-Becerril, Ismael Mancilla-Herrera
      Abstract: ProblemBreastfeeding's influence on the tolerance to environmental antigens is essential for short- and long-term homeostasis for children. Colostrum is rich in leucocytes, but it is unknown whether regulatory T cells (Treg) account for part of this cell population.Method of studyFrequencies of CD127− CD25++ Treg and levels of immunoregulatory-associated cell markers were determined in colostrum and were compared with autologous blood cells. In addition, we evaluated whether the birth conditions can affect these features.ResultsHigher frequencies of CD127 −CD25++ Treg cells expressing Foxp3 and CD45RO were observed in the colostrum. The cells’ CD25, CD152, CD279, and TGF-β expression levels were greater than those in autologous blood cells. In addition, the CD279 and TGF-β expressions of colostrum CD127− CD25++ Treg cells were influenced by gestational age and delivery mode.ConclusionThe higher proportion of these cells with a function-associated phenotype may reflect certain tolerogenic effects of breastmilk on newborns and infants, contributing to immune system homeostasis.Helper T cells with CD127− CD25++ phenotype (Treg) were identified in colostrum by flow cytometry (a). Colostrum Treg cells express the transcription factor Foxp3 (b), and their frequencies are higher than those in autologous blood(c).
      PubDate: 2017-12-22T05:24:30.406732-05:
      DOI: 10.1111/aji.12806
  • Plasma immunological markers in pregnancy and cord blood: A possible link
           between macrophage chemo-attractants and risk of childhood type 1 diabetes
    • Authors: Maria Vistnes; German Tapia, Karl Mårild, Øivind Midttun, Per M. Ueland, Marte K. Viken, Per Magnus, Jens P. Berg, Kathleen M. Gillespie, Torild Skrivarhaug, Pål R. Njølstad, Geir Joner, Ketil Størdal, Lars C. Stene
      Abstract: ProblemPrevious studies have suggested that immune perturbations during pregnancy can affect offspring type 1 diabetes (T1D) risk. We aimed to identify immunological markers that could predict offspring T1D or that were linked to T1D risk factors.Method of studyWe quantified selected circulating immunological markers in mid-pregnancy (interleukin [IL]-1β, IL-1ra, IL-2Rα, IL-2, -4, -5, -6, -10, -12p70, 13, -17A, GM-CSF, IFN-γ, CXCL10, CCL 2, CCL3, CCL4, TNF) and cord blood plasma (neopterin and kynurenine/tryptophan ratio) in a case-control study with 175 mother/child T1D cases (median age 5.8, range 0.7-13.0 years) and 552 controls.ResultsPre-pregnancy obesity was positively associated with CCL4, CXCL10, kynurenine/tryptophan ratio and neopterin (P 
      PubDate: 2017-12-20T00:06:00.594858-05:
      DOI: 10.1111/aji.12802
  • The possible role of CD8+/Vα7.2+/CD161++ T (MAIT) and
           CD8+/Vα7.2+/CD161lo T (MAIT-like) cells in the pathogenesis of
           early-onset pre-eclampsia
    • Authors: Matyas Meggyes; Julia Szanto, Adrienn Lajko, Balint Farkas, Akos Varnagy, Peter Tamas, Eszter Hantosi, Eva Miko, Laszlo Szereday
      Abstract: ProblemThe objective of this study was to compare the expressions of different immune-checkpoint molecules by MAIT and MAIT-like cells in healthy pregnancy and in early-onset pre-eclampsia.Method of studyPeripheral blood mononuclear cells (PBMC) were stained with monoclonal antibodies to characterize MAIT and MAIT-like cells. Flow cytometric analyses were used to measure PD-1, TIM-3, activation markers, and intracellular perforin expression.ResultsWe identified CD3+/CD8+/Vα7.2+/CD161++ MAIT cells and a minor cell population characterized by CD3+/CD8+/Vα7.2+/CD161lo surface markers. In measuring the expression of PD-1 receptor, we found a significantly lower expression by MAIT cells in women with early-onset pre-eclampsia. CD69 expression by MAIT cells was significantly elevated in early-onset pre-eclamptic patients. Intracellular perforin content by MAIT and PD-1+ MAIT cells was significantly increased in pre-eclamptic patients compared with healthy individuals.ConclusionAltered frequency and reduced PD-1 expression combined together with the elevated perforin content of MAIT cells insinuate their potential roles in the pathogenesis of early-onset pre-eclampsia.
      PubDate: 2017-12-19T03:57:02.295926-05:
      DOI: 10.1111/aji.12805
  • Maternal history of recurrent pregnancy loss is associated with increased
           risk for long-term pediatric gastrointestinal morbidity in the offspring
    • Authors: Yael Lichtman; Eyal Sheiner, Tamar Wainstock, Idit Segal, Daniella Landau, Asnat Walfisch
      Abstract: ProblemRecurrent pregnancy loss (RPL) potentially involves an abnormal maternal inflammatory response. We investigated whether children of mothers with a history of RPL are at an increased risk for childhood gastrointestinal (GI) morbidity, with a specific focus on inflammatory bowel diseases (IBD).Method of studyA population-based cohort analysis comparing the risk for long-term GI morbidity in children born to mothers with and without a history of RPL. Gastrointestinal (GI) morbidity included hospitalizations involving a pre-defined set of ICD-9 codes.ResultsDuring the study period, 242 186 newborns met the inclusion criteria; 5% of which were offspring to mothers with a history of RPL. Gastrointestinal morbidity was significantly more common in the RPL group (6.6% vs 5.3%). Specifically, offspring to mothers with a history of RPL had significantly higher rates of IBD (2.1% vs 1.7%).ConclusionMaternal history of RPL is associated with an increased risk for pediatric GI morbidity in the offspring.
      PubDate: 2017-12-15T03:53:45.774222-05:
      DOI: 10.1111/aji.12799
  • IL-17 in neonatal health and disease
    • Authors: Shelley M. Lawrence; Jessica Lauren Ruoss, James L. Wynn
      Abstract: Over the last few years, scientific interest in the cytokine IL-17A has intensified as its role in human health and disease has been elucidated. Discovered almost a quarter century ago, IL-17A is known to have poor biologic activity when acting alone, but attains robust actions when working synergistically with potent mediators of proinflammatory immune responses, such as IL-6 and IL-8. IL-17A is produced by specialized innate immune cells that protect host barriers from the outside world. Like sentries, these innate immune cells can “sound the alarm” through increased production of IL-17A, causing activation and recruitment of primed neutrophils and monocytes when pathogens escape initial host defenses. In this way, IL-17A promulgates mechanisms responsible for pathogen death and clearance. However, when IL-17A pathways are triggered during fetal development, due to chorioamnionitis or in utero inflammatory conditions, IL-17A can instigate and/or exacerbate fetal inflammatory responses that increase neonatal morbidities and mortality associated with common neonatal conditions such as sepsis, bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), and necrotizing enterocolitis (NEC). This review details the ontogeny of IL-17A in the fetus and newborn, discusses how derangements in its production can lead to pathology, and describes known and evolving therapies that may attenuate IL-17A–mediated human conditions.
      PubDate: 2017-12-15T03:53:05.230596-05:
      DOI: 10.1111/aji.12800
  • Issue Information
    • PubDate: 2017-12-10T23:29:22.313273-05:
      DOI: 10.1111/aji.12746
  • Vitamin D facilitates trophoblast invasion through induction of
           epithelial-mesenchymal transition
    • Authors: Ryang Hee Kim; Byung Jun Ryu, Ki Mo Lee, Jae Won Han, Sung Ki Lee
      Abstract: ProblemVitamin D deficiency increases the risk of developing pregnancy-related complications, including preeclampsia and small-for-gestational-age infants. Vitamin D was demonstrated to promote the invasiveness of human extravillous trophoblasts (EVTs). However, whether vitamin D induces the epithelial-mesenchymal transition (EMT) of EVTs remains unclear. Therefore, we investigated whether vitamin D promotes EMT and the related signaling pathways.Method of studyIn this study, we performed EMT experiments using JAR cells based on the expression of the mesenchymal markers and vitamin D receptor. JAR cells were treated with calcitriol, the active form of vitamin D. Western blotting was performed to evaluate EMT markers and key molecules of signaling pathways. Invasion assays were conducted. Expression and secretion of MMPs were analyzed by real-time PCR and zymography.ResultsCalcitriol significantly enhanced EMT and the invasive capability of JAR cells, along with increased expression and secretion of MMP-2 and MMP-9. Moreover, ERK signaling pathway was activated by calcitriol. The effects of calcitriol were neutralized by ERK signaling blocker.ConclusionCalcitriol facilitated EMT induction and expression of MMPs via ERK signaling pathway, which promoted the invasive capability of EVTs. Further studies are warranted to elucidate the potential application of vitamin D in the prevention of pregnancy complications.
      PubDate: 2017-12-04T00:36:28.103543-05:
      DOI: 10.1111/aji.12796
  • Maternal CD8+ T-cell depletion alleviates intrauterine
           inflammation-induced perinatal brain injury
    • Authors: Jun Lei; Li Xie, Hongxi Zhao, Candice Gard, Julia L. Clemens, Michael W. McLane, Mia C. Feller, Maide Ozen, Christopher Novak, Wael Alshehri, Nader Alhejaily, Yahya Shabi, Jason M. Rosenzweig, Andrea Facciabene, Irina Burd
      Abstract: We investigated the mechanisms by which CD8+ T-cell trafficking in placenta contributes to perinatal brain injury by studying effects of maternal CD8+ T-cell depletion (DEP) in a mouse model of intrauterine inflammation (IUI). Maternal CD8+ T cells were depleted with anti-CD8+ antibodies. IUI was induced with lipopolysaccharide (LPS). DEP was confirmed using flow cytometry. Preterm birth rate was evaluated. Offspring neurologic sequelae were assessed by Nissl staining, immune arrays, confirmatory individual TaqMan® gene assays, and neurobehavioral tests. DEP did not significantly prevent LPS-induced preterm birth but improved neurobehavioral performance (P 
      PubDate: 2017-12-04T00:30:40.825867-05:
      DOI: 10.1111/aji.12798
  • Paternal HLA-C is a risk factor in unexplained recurrent miscarriage
    • Authors: Tess Meuleman; Geert W. Haasnoot, Jan M. M. Lith, Willem Verduijn, Kitty W. M. Bloemenkamp, Frans H. J. Claas
      Abstract: ProblemHLA-C is the only classical HLA-I antigen expressed on trophoblast. We hypothesized that the alloimmune response to paternal HLA-C plays a role in unexplained recurrent miscarriage.Method of studyIn a case-control design, we included 100 women with at least three unexplained consecutive miscarriages along with their partners and children. For the first control group, we included 90 women with an uneventful singleton pregnancy without pregnancy complications in their history along with their children. The second control group consisted of 425 families. HLA-C*07 and HLA-C*17 frequencies, which are the most immunogenic HLA-C antigens, along with HLA-C mismatches, and the presence of specific HLA antibodies in the mother were determined.ResultsHLA-C and HLA-C*07 mismatches were significantly increased in couples with recurrent miscarriage compared to control subjects (P = .016, P = .008, respectively). The incidence of child-specific HLA-C*07/HLA-C*17 antibodies was increased in women with recurrent miscarriage (P = .007).ConclusionThe results show that HLA-C incompatibility between couples is significantly associated with unexplained recurrent miscarriage.HLA-C incompatibility between couples is significantly associated with unexplained recurrent miscarriage. An increased number of mismatches for HLA-C*07 between mother and father in unexplained recurrent miscarriage and increased presence of child-specific HLA-C*07/17 antibodies in women with unexplained recurrent miscarriage is found.
      PubDate: 2017-12-04T00:30:23.161539-05:
      DOI: 10.1111/aji.12797
  • Immune checkpoint molecules soluble program death ligand 1 and galectin-9
           are increased in pregnancy
    • Authors: Elizabeth Ann L. Enninga; Susan M. Harrington, Douglas J. Creedon, Rodrigo Ruano, Svetomir N. Markovic, Haidong Dong, Roxana S. Dronca
      Abstract: ProblemPregnancy requires balance between tolerance to the haploidentical fetus and the mother's ability to mount immune responses. There are parallels to this phenomenon that occur in metastatic cancer. We assessed soluble program death ligand-1 soluble PD-L1 (sPD-L1) and galectin-9 in the blood of pregnant women during gestation as these molecules are highly involved in immune suppression during cancer.Method of studyMaternal blood was collected from 30 primigravida women at monthly intervals during pregnancy, delivery and 6-week post-partum. Blood was analyzed for sPD-L1 and galectin-9 concentrations by ELISA. Term placentas were collected in formalin and IHC was completed for PD-L1 and galectin-9 expression.ResultsMaternal blood levels of sPD-L1 (0.438 ng/mL) and galectin-9 (1976 pg/mL) were elevated early in normal pregnancies compared to non-pregnant controls (0.242 ng/mL and 773 pg/mL, respectively). sPD-L1 increased throughout gestation, whereas galectin-9 remained elevated until parturition; both proteins returned to control levels post-partum. Women carrying male fetuses had significantly higher galectin-9 levels, but not sPD-L1, than those carrying females (2263 pg/mL vs 1874 pg/mL; P = .0005). Trophoblast cells of the term placenta coexpress galectin-9 and PD-L1.ConclusionImmune-regulatory molecules galectin-9 and sPD-L1 increased during pregnancy and may play a role in immune tolerance that is critical for the fetus.Normal human pregnancy is associated with increased levels of immunosuppressive soluble program death ligand-1 (sPD-L1) and galectin-9.
      PubDate: 2017-12-04T00:26:16.06038-05:0
      DOI: 10.1111/aji.12795
  • Decidual CD68+HLA-DR+CD163− M1 macrophages increase in miscarriages with
           normal fetal chromosome
    • Authors: Shigeki Shimada; Yasuhiko Ebina, Norifumi Iijima, Masashi Deguchi, Hideto Yamada
      Abstract: ProblemIs an abnormal increase or decrease of M1/M2 macrophages observed in the deciduae of miscarriages with normal fetal chromosome (MN)'Methods of studyDeciduae of 18 MN and 26 miscarriages with abnormal fetal chromosome (MA) were obtained. Additionally, deciduae from 15 women whose pregnancies ended in induced abortions (IA) and endometriums at the mid-luteal phase from 19 non-pregnant women endomeriums of mid-luteal phases (EM) were obtained. Macrophages were analyzed by flow cytometry using monoclonal antibodies for CD68, HLA-DR, and CD163.ResultsM1 macrophages, defined as CD68+HLA-DR+CD163− cells, increased in MN compared with MA or IA. M2 macrophages, defined as CD68+HLA-DR−CD163+ cells, increased in the deciduae of MA and IA compared with EM. However, this increase was not observed in the deciduae of MN.ConclusionOur findings of phenotypic characters of decidual macrophages in MN provide additional evidence that M2 polarization is favorable for the maintenance of early stages of pregnancy.
      PubDate: 2017-12-02T02:01:19.156205-05:
      DOI: 10.1111/aji.12791
  • Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of
           ovarian endometriomas as candidate biomarkers of endometriosis
    • Authors: Carla Trapero; Lluis Jover, Maria Eulàlia Fernández-Montolí, Amparo García-Tejedor, August Vidal, Inmaculada Gómez de Aranda, Jordi Ponce, Xavier Matias-Guiu, Mireia Martín-Satué
      Abstract: ProblemThe diagnosis of endometriosis, a prevalent chronic disease with a strong inflammatory component, is usually delayed due to the lack of noninvasive diagnostic tests. Purinergic signaling, a key cell pathway, is altered in many inflammatory disorders. The aim of the present work was to evaluate the levels of adenosine deaminase (ADA), alkaline phosphatase (ALP), ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and ENPP3, elements of purinergic signaling, as biomarker candidates for endometriosis.Method of studyA case-control comparative study was conducted to determine ADA, ALP, ENPP1 and ENPP3 levels in echo-guided aspirated fluids of endometriomas (case group) and simple ovarian cysts (control group) using the ELISA technique.ResultsAdenosine deaminase, ALP, ENPP1, and ENPP3 were present and quantifiable in the contents of endometriomas and simple cysts. There were significant differences in ADA and ENPP1 levels in endometriomas in comparison with simple cysts (2787 U/L and 103.9 ng/mL more in endometriomas, for ADA and ENPP1, respectively). Comparisons of ALP and ENPP3 levels between the two groups did not reveal significant differences.ConclusionThe ectoenzymes ADA and ENPP1 are biomarker candidates for endometriosis.
      PubDate: 2017-11-30T04:26:22.895876-05:
      DOI: 10.1111/aji.12794
  • Oxidative stress diseases unique to the perinatal period: A window into
           the developing innate immune response
    • Authors: Robert M. Dietz; Clyde J. Wright
      Abstract: The innate immune system has evolved to play an integral role in the normally developing lung and brain. However, in response to oxidative stress, innate immunity, mediated by specific cellular and molecular programs and signaling, contributes to pathology in these same organ systems. Despite opposing drivers of oxidative stress, namely hyperoxia in neonatal lung injury and hypoxia/ischemia in neonatal brain injury, similar pathways—including toll-like receptors, NFκB and MAPK cascades—have been implicated in tissue damage. In this review, we consider recent insights into the innate immune response to oxidative stress in both neonatal and adult models to better understand hyperoxic lung injury and hypoxic-ischemic brain injury across development and aging. These insights support the development of targeted immunotherapeutic strategies to address the challenge of harnessing the innate immune system in oxidative stress diseases of the neonate.The innate immune system has evolved to play an integral role in the normally developing lung and brain. However, in response to oxidative stress, innate immunity, mediated by specific cellular and molecular programs and signaling, contributes to pathology in these same organ systems. Despite opposing drivers of oxidative stress, namely hyperoxia in neonatal lung injury and hypoxia/ischemia in neonatal brain injury, many of the same players such as toll-like receptors, NFκB, and MAPK cascades play similar roles to damage tissue. In this review, we consider recent insights into the innate immune response to oxidative stress in both neonatal and adult models to better understand hyperoxic lung injury and hypoxic-ischemic brain injury across development and aging. These insights support the development of targeted immunotherapeutic strategies to address the challenge of harnessing the innate immune system in oxidative stress diseases of the neonate.
      PubDate: 2017-11-30T04:25:31.211556-05:
      DOI: 10.1111/aji.12787
  • A distinct mechanism of senescence activation in amnion epithelial cells
           by infection, inflammation, and oxidative stress
    • Authors: Christopher Luke Dixon; Lauren Richardson, Samantha Sheller-Miller, George Saade, Ramkumar Menon
      Abstract: ProblemWe investigated p38MAPK activation-induced fetal membrane cell senescence in response to inflammation (tumour necrosis factor-alpha [TNF-α]) and infection (lipopolysaccharide [LPS]), factors associated with spontaneous preterm birth.Method of studyPrimary amnion epithelial cells (AECs) were exposed to TNF-α, 50 ng/mL and LPS, 100 ng/mL. Cigarette smoke extract (CSE), a known OS inducer, was used as positive control. AECs were cotreated with the antioxidant N-acetyl cysteine (NAC) and p38MAPK inhibitor SB203580 to determine the effect of OS and p38MAPK. Western blot analysis was performed for active (Phospho-p38MAPK) and total p38MAPK. Senescence was determined by flow cytometry, and culture supernatants were tested for IL-6 using ELISA.ResultsTNF-α, but not LPS, increased p38MAPK activation compared to untreated cells (P = .01). The number of senescent cells and senescence-associated IL-6 was higher in both TNF-α and LPS-treated cells compared to control (P = .001, P = .01, respectively). Antioxidant NAC inhibited p38MAPK activation by TNF-α. p38MAPK inhibitor SB203580 reduced the development of senescence and IL-6 by TNF-α and LPS. CSE treatment validated our current data.ConclusionTNF-α caused OS-mediated p38MAPK induction, senescence, and IL-6 increase from AECs. LPS also induced senescence and IL-6 increase. Inflammatory and infectious factors may cause premature fetal cell senescence contributing to preterm birth pathophysiology.
      PubDate: 2017-11-30T04:20:28.535573-05:
      DOI: 10.1111/aji.12790
  • Amniotic fluid pentraxins: Potential early markers for identifying
           intra-amniotic inflammatory complications in preterm pre-labor rupture of
    • Authors: Ivana Musilova; Ctirad Andrys, Jan Krejsek, Marcela Drahosova, Barbora Zednikova, Lenka Pliskova, Helena Zemlickova, Bo Jacobsson, Marian Kacerovsky
      Abstract: In this study, pentraxin 3 (PTX3), C-reactive protein (CRP), and serum amyloid P component (SAP) concentrations in the amniotic fluid of women with preterm pre-labor rupture of membranes (PPROM) were evaluated based on evidence of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI. A total of 149 women with PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid PTX3, SAP, and CRP concentrations were assessed using enzyme-linked immunosorbent assay. PTX3 and CRP concentrations were higher in women with MIAC, IAI, and microbial-associated IAI than in women without these conditions. SAP concentrations were only higher in the presence of IAI and microbial-associated IAI. Amniotic fluid PTX3 concentrations of 11 ng/mL were found to be the best value for identifying the presence of microbial-associated IAI and IAI in women with PPROM. To conclude, amniotic fluid pentraxins are involved in intra-amniotic inflammatory responses in pregnancies complicated by PPROM.
      PubDate: 2017-11-28T07:15:34.140168-05:
      DOI: 10.1111/aji.12789
  • Placental exosomes: A proxy to understand pregnancy complications
    • Authors: Jin Jin; Ramkumar Menon
      Abstract: Exosomes (30- to 150-nm particles), originating from multivesicular bodies by the invagination of the endosomal membrane, are communication channels between cells. Exosomes are released by various cell types and cargo proteins, lipids, and nucleic acids reflecting the physiologic status of their cells of origin and cause functional changes in recipient cells, which are likely dependent on their quantity and/or cargo contents. Recently, placental exosomes, produced by various placental cell types, have been isolated from maternal blood using the placental protein-specific marker, placental alkaline phosphatase (PLAP). PLAP-positive exosomes are seen in maternal blood as early as the first trimester of pregnancy and increase as gestation progresses, with maximum numbers seen at term. Although the functional relevance of placental exosomes is still under investigation, several studies have linked placental exosomes changes (quantity and cargo) reflecting placental dysfunctions associated with adverse pregnancy events. As placental exosomes can be isolated from maternal blood, they are liquid biopsies reflecting placental functions. Hence, they are useful as biomarkers of placental functions and dysfunctions obtainable through non-invasive approaches. This review summarizes the biogenesis, release, and functions of exosomes and specifically expounds the role of placental-specific exosomes and their significance associated with pregnancy complications.
      PubDate: 2017-11-28T07:11:28.543552-05:
      DOI: 10.1111/aji.12788
  • Therapy for antiphospholipid miscarriages: Throwing the baby out with the
    • Authors: Cecilia Beatrice Chighizola; Yehuda Shoenfeld, Pier Luigi Meroni
      Abstract: ProblemThe association of low molecular weight heparin (LMWH) with low-dose aspirin (LDASA) provides the therapeutic cornerstone of obstetric anti-phospholipid syndrome (APS). This combo approach is not effective in all patients, and few women still experience recurrences.Method of StudyIn an elegant in vitro study, Chiombori Quao and colleagues demonstrated that anti-phospholipid antibodies (aPL) affect the functionality of endometrial endothelial cells interfering with angiogenesis. LMWH and LDASA, in combination or alone, did not display any protective activity but exacerbated aPL-mediated effects.ResultsThe above data were advocated as a demonstration of the inefficacy of LMWH and LDASA in obstetric APS. Given the lack of thrombotic lesions in APS placentae, this treatment is mainly empirical. However, clinical practice clearly shows that LMWH and LDASA are effective in most patients. Non-responsive women represent a peculiar subgroup, with a high-risk aPL profile. All experimental models, including in vitro models of obstetric APS, display limitations that should be considered before translating data to patients. In particular, the use of a monoclonal antibody specific for Domain (D) 5 does not fit with the evidence that anti-D1, but not anti-D4,5, are associated with both vascular and obstetric APS manifestations.ConclusionsThe association of LMWH and LDASA is the most effective therapeutic option for pregnant aPL-positive women. The lack of a clear demonstration of the pharmacological action of LMWH/LDASA should urge to further invtrestigate the pathophysiology of aPL-associated miscarriages.
      PubDate: 2017-11-28T07:11:20.799235-05:
      DOI: 10.1111/aji.12792
  • Chemokine (C-C motif) ligand 25 expressed by trophoblast cells and
           leukocytes bearing its receptor Ccr9: An alliance during embryo
    • Authors: Rodrigo Barbano Weingrill; Mara S. Hoshida, Ciro Dresch Martinhago, Simone Correa-Silva, Elaine Cardoso, Patrícia Palmeira, Claudio Romero Farias Marinho, Estela Bevilacqua
      Abstract: ProblemWe hypothesized that trophoblast expression of Ccl25 attracts a specific leukocyte cell population to the implantation site for local regulation.Method of studyMice blastocysts, ectoplacental cones, and decidua at gestational days 3.5-7.5 were evaluated for Ccl25 and Ccr9 expressions. Peripheral availability and characterization of Ccr9+ leukocytes were determined by flow cytometry. Leukocyte chemotaxis was assessed in the presence of Ccl25 recombinant protein and embryos using antisense oligomers (ODNs) to Ccl25 and Ccr9 neutralizing antibody.ResultsCcl25 was expressed by embryonic cells, whereas Ccr9 expression was strong at the maternal compartment and in PBMC. Immunolocalization confirmed this expression. In vitro, chemotaxis assays showed that the embryonic Ccl25 signals to Ccr9+ PBMCs. Maternal Ccr9+α4β7+ monocytes switch from an anti-inflammatory phenotype (F4/80+11b+Ly6C-TGF-β+ cells, pre-implantation) to an inflammatory profile (F4/80+11b+Ly6C+TNF-α+ cells, post-implantation).ConclusionOur data support the establishment of a CCL25/CCR9-axis at the maternal-fetal interface in mice, which may be involved in immune regulatory mechanisms during embryo implantation.Immunolocalization of Ccr9 (green, FITC) and Ccl25 (red, TRITC) at the maternal-fetal interface on gd3.5 (A and B), gd5.5 (C and D) and, in a gd7.5-ectoplacental cone (E-H). Ccl25 (B, arrowheads) stained the luminal uterine epithelial cells (le) and, Ccr9 (A and B, arrows) the deeper layers of the endometrium. FITC-Ccr9+ cells (C and D, arrows) is also seen surrounding a maternal blood vessel (mv) in the mesometrial decidua (md). On gd7.5, Ccr9 reactive cells have leukocyte-like morphological characteristics (G-H, arrowheads) and are inserted between Ccl25 positive cells (F, H) of the ectoplacental cone (ec). (H, merged image). I, Relative quantification obtained by RT-qPCR of Ccr9 at the endometrial compartment, during embryo implantation. *P
      PubDate: 2017-11-20T06:10:50.786851-05:
      DOI: 10.1111/aji.12783
  • The role of indoleamine-2,3-dioxygenase in normal and pathological
    • Authors: Rui-Qi Chang; Da-Jin Li, Ming-Qing Li
      Abstract: The survival of allogeneic fetus during pregnancy contradicts the laws of immune responses. Behind this paradoxical phenomenon, the mechanism is quite complex. Indoleamine-2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism. Emerging evidence shows that IDO is expressed at the maternal-fetal interface, including trophoblast cells, decidual stroma cells, decidual immune cells (eg, natural killer cells, T cells, and macrophages), and vascular endothelial cells of decidua and chorion. Moreover, the expression and activity of IDO are different among non-pregnant, normal pregnant, and pathological pregnant conditions. IDO plays important roles in normal pregnancy through immune suppression and regulation of fetal invasion and circulation. However, the abnormal expression and dysfunction of IDO are associated with some pathological pregnancies (including recurrent spontaneous abortion, preeclampsia, preterm labor, and fetal growth restriction).
      PubDate: 2017-11-20T06:05:21.64032-05:0
      DOI: 10.1111/aji.12786
  • The role of immunological testing and intervention in reproductive
           medicine: A fertile collaboration'
    • Authors: Syed B. Ali; Yogesh Jeelall, Craig E. Pennell, Roger Hart, Andrew McLean-Tooke, Michaela Lucas
      Abstract: Advances in reproductive medicine have significantly increased the success of fertility treatments. Nevertheless, some women experience recurrent implantation failure (RIF) after in-vitro fertilization (IVF) or recurrent pregnancy loss (RPL). Imbalances in the immune system and failure to achieve immune tolerance to the foetus have been implicated as potentially modifiable causes of idiopathic RIF and RPL. As such, women are increasingly being treated with immunomodulatory agents in an attempt to achieve a successful pregnancy. This systematic review examines the published evidence on immune changes in these patients, the use of immunomodulation therapies and diagnostic testing modalities to guide their use or to identify patient subsets most likely to benefit. The PubMed database was searched for the terms “recurrent implantation failure” and “recurrent pregnancy loss” in conjunction with T-helper (Th) cells and their subsets in particular; Th1, Th2, Th17 and T-regulatory (Treg) cells, natural killer (NK) cells, cytokine imbalance as well as immune modulators and immune suppressants. The reference lists of articles were examined to identify additional articles. There remains limited data on the immunological changes in cytokine and cellular profiles during the hormonal cycle as well as prior to, during and after implantation in health as well as idiopathic RIF and RPL. There is a need to advance immunological diagnostics to match the clinical need in this emerging field and to guide clinicians to make optimal and safe therapeutic choices. It is also imperative that the well-being of the infants conceived after such intervention is monitored.
      PubDate: 2017-11-20T05:55:22.677507-05:
      DOI: 10.1111/aji.12784
  • Rapid and simple detection of Ureaplasma species from vaginal swab samples
           using a loop-mediated isothermal amplification method
    • Authors: Kazumasa Fuwa; Mitsuko Seki, Yoshiyasu Hirata, Itaru Yanagihara, Yukiko Nakura, Chika Takano, Kazumichi Kuroda, Satoshi Hayakawa
      Abstract: ProblemUreaplasma species occasionally cause chorioamnionitis and premature labor. We developed a novel assay employing a loop-mediated isothermal amplification (LAMP) method to detect Ureaplasma parvum and Ureaplasma urealyticum.Method of studyLoop-mediated isothermal amplification primers were designed to amplify Ureaplasma-specific ureaseB genes. Four U. parvum strains, 5 U. urealyticum strains and 14 reference bacterial species were evaluated. Forty-six vaginal swab samples were analyzed by LAMP, culture, and PCR.ResultsOur LAMP primers were specific to each species and had no cross-reaction. Of 46 clinical specimens, the sensitivity, specificity, and positive and negative predictive values of the LAMP method were 100% (12/12), 100% (34/34), 100% (12/12), and 100% (34/34), respectively, whereas those of PCR were 66.7% (8/12), 100% (34/34), 100% (8/8), and 89.5% (34/38), respectively, compared to culture-based detection.ConclusionThe LAMP detection method outperformed the culture and PCR methods. Early detection enables appropriate antibiotic selection for improved prenatal outcomes.We established novel LAMP detection system for Ureaplasma parvum and Ureaplasma urealyticum. Serially diluted Ureaplasma parvum DNA (The upper panel) and Ureaplasma urealyticum DNA (The lower panel) was amplified and showed positive results over 102 copies/reaction. This system outperforms single round PCR in sensitivity and specificity.
      PubDate: 2017-11-20T05:36:09.058785-05:
      DOI: 10.1111/aji.12771
  • Chronic endometritis in patients with unexplained infertility: Prevalence
           and effects of antibiotic treatment on spontaneous conception
    • Authors: Ettore Cicinelli; Maria Matteo, Giueseppe Trojano, Paola C. Mitola, Raffaele Tinelli, Amerigo Vitagliano, Francesco M. Crupano, Achiropita Lepera, Giuseppe Miragliotta, Leonardo Resta
      Abstract: ProblemThe correlations between chronic endometritis and unexplained infertility are unexplored.Method of StudyWe performed a retrospective study on consecutive patients referred to our hysteroscopy service due to unexplained infertility. All women underwent endometrial sampling with histological and cultural examinations. If chronic endometritis was diagnosed, patients received antibiotic therapy, and chronic endometritis resolution was subsequently ascertained by histological examination. We aimed to estimate chronic endometritis prevalence and the effects of antibiotic therapy on spontaneous conception during the year following hysteroscopy.ResultsA total number of 95 women were included. Pooled prevalence of chronic endometritis was 56.8%. Antibiotic therapy resulted in chronic endometritis resolution in 82.3% of patients, while in 17.6% disease was persistent. Women with cured chronic endometritis showed higher pregnancy rate and live birth rate in comparison with both women with persistent disease and women without chronic endometritis diagnosis (pregnancy rate = 76.3% vs 20% vs 9.5%, P 
      PubDate: 2017-11-14T05:55:50.772477-05:
      DOI: 10.1111/aji.12782
  • Low molecular weight heparin and aspirin exacerbate human endometrial
           endothelial cell responses to antiphospholipid antibodies
    • Authors: Zola Chihombori Quao; Mancy Tong, Elena Bryce, Seth Guller, Lawrence W. Chamley, Vikki M. Abrahams
      Abstract: ProblemWomen with antiphospholipid antibodies (aPL) are at risk for pregnancy complications despite treatment with low molecular weight heparin (LMWH) or aspirin (ASA). aPL recognizing beta2 glycoprotein I can target the uterine endothelium, however, little is known about its response to aPL. This study characterized the effect of aPL on human endometrial endothelial cells (HEECs), and the influence of LMWH and ASA.Method of studyHEECs were exposed to aPL or control IgG, with or without low-dose LMWH and ASA, alone or in combination. Chemokine and angiogenic factor secretion were measured by ELISA. A tube formation assay was used to measure angiogenesis.ResultsaPL increased HEEC secretion of pro-angiogenic VEGF and PlGF; increased anti-angiogenic sFlt-1; inhibited basal secretion of the chemokines MCP-1, G-CSF, and GRO-α; and impaired angiogenesis. LMWH and ASA, alone and in combination, exacerbated the aPL-induced changes in the HEEC angiogenic factor and chemokine profile. There was no reversal of the aPL inhibition of HEEC angiogenesis by either single or combination therapy.ConclusionBy aPL inhibiting HEEC chemokine secretion and promoting sFlt-1 release, the uterine endothelium may contribute to impaired placentation and vascular transformation. LMWH and ASA may further contribute to endothelium dysfunction in women with obstetric APS.
      PubDate: 2017-11-14T05:55:36.978715-05:
      DOI: 10.1111/aji.12785
  • Genetic and epigenetic regulation of major histocompatibility complex
           class I gene expression in bovine trophoblast cells
    • Authors: Bi Shi; Aaron J. Thomas, Abby D. Benninghoff, Benjamin R. Sessions, Qinggang Meng, Parveen Parasar, Heloisa M. Rutigliano, Kenneth L. White, Christopher J. Davies
      Abstract: ProblemThe regulatory mechanisms governing differential expression of classical major histocompatibility complex (MHC) class I (MHC-Ia) and non-classical MHC class I (MHC-Ib) genes are poorly understood.Method of studyQuantitative reverse transcription- polymerase chain reaction (PCR) was used to compare the abundance of MHC-I transcripts and related transcription factors in peripheral blood mononuclear cells (PBMC) and placental trophoblast cells (PTC). Methylation of MHC-I CpG islands was detected by bisulfite treatment and next-generation sequencing. Demethylation of PBMC and PTC with 5′-aza-deoxycytidine was used to assess the role of methylation in gene regulation.ResultsMHC-I expression was higher in PBMC than PTC and was correlated with expression of IRF1, class II MHC transactivator (CIITA), and STAT1. The MHC-Ia genes and BoLA-NC1 were devoid of CpG methylation in PBMC and PTC. In contrast, CpG sites in the gene body of BoLA-NC2, -NC3, and -NC4 were highly methylated in PBMC but largely unmethylated in normal PTC and moderately methylated in somatic cell nuclear transfer PTC. In PBMC, demethylation resulted in upregulation of MHC-Ib by 2.8- to 6-fold, whereas MHC-Ia transcripts were elevated less than 2-fold.ConclusionDNA methylation regulates bovine MHC-Ib expression and is likely responsible for the different relative levels of MHC-Ib to MHC-Ia transcripts in PBMC and PTC.qRT-PCR analysis of bovine MHC-I and transcription factor gene expression in PBMC and PTC. Data were normalized to GAPDH. The heatmap shows the fold change of gene expression relative to the average for the AI PTC samples.
      PubDate: 2017-11-12T23:20:36.225392-05:
      DOI: 10.1111/aji.12779
  • Inhibition of IAP (inhibitor of apoptosis) proteins represses inflammatory
    • Authors: Fuminori Taniguchi; Takashi Uegaki, Kazuomi Nakamura, Khine Yin Mon, Takashi Harada, Tetsuya Ohbayashi, Tasuku Harada
      Abstract: ProblemHow is the role of inhibitor of apoptosis proteins (IAPs) in the development of murine endometriosis lesions'Method of studyBALB/c female mice (n = 36) were used for the murine endometriosis model. Endometriotic lesions were surgically induced in mice by transplanting mouse uterine tissue. After 4 weeks of IAP antagonist (BV6) treatment, the expression of inflammatory factors in the implants was evaluated using real-time RT-PCR. Inflammatory state, angiogenic activity, and nuclear factor-kappa B (NF-κB) activation were assessed by immunohistochemical staining.ResultsThe number, size, and level of inflammatory cytokines (Vegf, Il-6, Ccl-2, Lif) gene expression in the murine endometriosis-like lesions were reduced by BV6 treatment. BV6 repressed the intensity and rate of positive cells of CD3, F4/80, and PECAM immunostaining; in addition, the expression of NF-κB p65 and phospho-NF-κB p65 was also attenuated.ConclusionInhibitor of apoptosis proteins antagonist represses the inflammation status of murine endometriosis-like lesions viaNF-κB pathway. IAPs may be a novel therapeutic target for endometriosis.
      PubDate: 2017-11-06T04:33:21.826035-05:
      DOI: 10.1111/aji.12780
  • Medroxyprogesterone acetate-treated human, primary endometrial epithelial
           cells reveal unique gene expression signature linked to innate immunity
           and HIV-1 susceptibility
    • Authors: Matthew W. Woods; Muhammad Atif Zahoor, Sara Dizzell, Chris P. Verschoor, Charu Kaushic
      Abstract: ProblemMedroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented.Method of studyUsing microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA.ResultsEach hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility.ConclusionThe analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition.Treatment of human endometrial epithelial cells with the hormonal contraceptive, Medroxyprogesterone acetate results in a unique gene expression signature linked to innate immunity and HIV-1 susceptibility.
      PubDate: 2017-11-06T04:22:29.243203-05:
      DOI: 10.1111/aji.12781
  • Breastfeeding and autoimmunity: Programing health from the beginning
    • Authors: Vânia Vieira Borba; Kassem Sharif, Yehuda Shoenfeld
      Abstract: Breast milk is not only a completely adapted nutrition source for the newborn but also an impressive array of immune-active molecules that afford protection against infections and shape mucosal immune responses. Decisive imprinting events might be modulated during the first months of life with potential health long-term effects, enhancing the importance of breastfeeding as a major influence on the immune system correct development and modifying disease susceptibility. The aim of this review was to clarify the link between breastfeeding and autoimmune diseases, inquiring the related mechanisms, based on data available in the literature. Being breastfed was associated with a lower incidence of diabetes, celiac disease, multiple sclerosis and asthma, explained by the protection against early infections, anti-inflammatory properties, antigen-specific tolerance induction, and regulation of infant's microbiome. The protective role of human milk in idiopathic juvenile arthritis, rheumatoid arthritis, and inflammatory bowel diseases remains controversial. On the other hand, the breastfeeding mother faces a health-challenging period in life. High levels of prolactin may lead either to the development of autoimmune diseases in susceptible mothers or exacerbations of current immune-mediated disorders. These features raise the question if mothers with autoimmune diseases, mainly systemic lupus erythematosus, should avoid breastfeeding.
      PubDate: 2017-10-30T06:08:27.052939-05:
      DOI: 10.1111/aji.12778
  • Upregulation of Tim-3 expression at feto-maternal interface may explain
           embryo survival in the CBAxDBA/2 model of abortion
    • Authors: Fanfan Li; Jing Dang, Min Jiang, Mengzhou He, Meitao Yang, Jing Li, Haiyan Hao, Yuan Zhou, Wei Zuo, Yin Xie, Dongrui Deng
      Abstract: ProblemTo understand the mechanisms of action of Tim-3 at the maternal-fetal interface and explore how Tim-3 might be involved in the pathogenesis of abortion by constructing an in vitro trophoblast-lymphocyte system.Methods of StudyFemale CBA/J × male DBA/2 matings were used as the abortion-prone model and CBA/J × male BALB/c matings as control. The expression of Tim-3 at the maternal-fetal interface and in the peripheral blood lymphocytes was measured by immunohistochemistry and Western blotting. The proliferation index of lymphocytes and levels of Th1/Th2-derived cytokines in peripheral blood and in the co-culture system were determined using CCK-8 assay and ELISA, respectively.ResultsThe expression level of Tim-3 was higher in abortion-prone matings than that of control (P 
      PubDate: 2017-10-30T04:15:54.893875-05:
      DOI: 10.1111/aji.12775
  • Gestational tissue inflammatory biomarkers at term labor:
           A systematic review of literature
    • Authors: Emily E. Hadley; Lauren S. Richardson, Maria R. Torloni, Ramkumar Menon
      Abstract: Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro- and anti-inflammatory biomarkers reported in intra-uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro- and anti-inflammatory biomarkers (mRNA and/or protein) reported in feto-maternal tissues during normal human term labor, published in English (1980-2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL-6, IL-8, IL-1β, COX-2, PGE-2, TNF-α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto-maternal compartments at term labor. Increase in pro-inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti-inflammatory markers at term labor are hardly reported.
      PubDate: 2017-10-27T01:25:24.800759-05:
      DOI: 10.1111/aji.12776
  • The immune profile induced is crucial to determine the effects of
           immunocastration over gonadal function, fertility, and GnRH-I expression
    • Authors: Daniela Siel; Alexandra Loaiza, Sonia Vidal, Mario Caruffo, Rodolfo Paredes, Galia Ramirez, Lisette Lapierre, Cristóbal Briceño, Oliver Pérez, Leonardo Sáenz
      Abstract: ProblemImmunocastration or vaccination against the GnRH-I hormone is a promising alternative to reproductive control in different animal species. Given the low immunogenicity of this hormone, the use of adjuvants becomes necessary.Method of StudyThis study evaluated the effects of three adjuvants that induce different immune response profiles over gonadal function, fertility, and expression of GnRH-I. Female mice (n = 6) were vaccinated at days 1 and 30 with a recombinant antigen for immunocastration and different adjuvants that induced preferentially Th1/Th2, Th2, and Th1 immune profiles.ResultsTh1/Th2 response is the most efficient to block reproductive activity in vaccinated animals, reducing the number of luteal bodies and pre-ovulatory follicles. Th2 and Th1/Th2 responses induced an increase in GnRH-I at the hypothalamus.ConclusionThe immune profile induced by different adjuvants is essential on the effects over fertility, gonadal function, and hypothalamic GnRH-I expression in immunocastrated animals.In female mice vaccinated with a recombinant antigen for immunocastration and different adjuvants that induced preferentially Th1/Th2, Th2, and Th1 immune profiles, the effects of vaccination over gonadal function, fertility, and expression of GnRH-I were evaluated.
      PubDate: 2017-10-19T06:21:28.856223-05:
      DOI: 10.1111/aji.12772
  • Computational flow cytometry analysis reveals a unique immune signature of
           the human maternal-fetal interface
    • Authors: Jessica Vazquez; Melina Chavarria, Yan Li, Gladys E. Lopez, Aleksandar K. Stanic
      Abstract: ProblemDecidual immune dysregulation is thought to underlie major pregnancy disorders; however, incomplete understanding of the decidual immune interface has hampered the mechanistic investigation.Method of studyHuman term decidua was collected, and single-cell phenotypic information was acquired by highly polychromatic flow cytometry. Cellular identity analysis was performed with t-distributed stochastic neighbor embedding, DensVM clustering, and matched to CellOntology database.ResultsTraditional analytical methods validated known cellular T and dendritic cell subsets in human term decidua. Computational analysis revealed a complex and tissue-specific decidual immune signature in both the innate and adaptive immune compartments.ConclusionPolychromatic flow cytometry with a streamlined computational analysis pipeline is a feasible approach to comprehensive immunome mapping of human term decidua. As an unbiased, standardized method of investigation, computational flow cytometry promises to unravel the immune pathology of pregnancy disorders.Use of high dimensional flow cytometry with operator-independent machine learning to comprehensively map T cell populations at the maternal-fetal interface. t-SNE map generated from pre-gated CD3+ cells from decidua basalis, decidua parietalis, and PBMCs (top) and manually gated subsets overlaid onto total CD3+ cells (bottom). Analysis revealed a unique immune signature, characteristic of term human decidua.
      PubDate: 2017-10-14T02:35:42.43803-05:0
      DOI: 10.1111/aji.12774
  • The CYCLOCALYX study: Ovulatory cycle affects circulating compartments of
           the endothelial glycocalyx in blood
    • Authors: Nikolai Hulde; Nina Rogenhofer, Florian Brettner, Nicole C. Eckert, Isabella Götzfried, Thu Nguyen, Judith-I. Pagel, Tobias Kammerer, Klaus F. Hofmann-Kiefer, Gustav Schelling, Andreas Dendorfer, Markus Rehm, Christian J. Thaler
      Abstract: ProblemThe endothelial glycocalyx (EGX) plays an important role in vascular integrity. Recently, increased levels of EGX components were detected in the circulating blood of healthy pregnant women and were related to the increased tendency to edema formation during gestation. However, the EGX has not yet been systematically studied in non-pregnant women during ovulatory cycles.Method of studySerum levels of EGX components syndecan-1, heparan sulfate, and hyaluronan in healthy women (n = 16) at 3 phases of the ovulatory cycle (early follicular phase, at ovulation, and mid-luteal phase) were compared with a control group of healthy men (n = 10). Using immunofluorescence microscopy in cultured human umbilical vein endothelial cells, the effects of progesterone and estrogen on the EGX were measured.ResultsSyndecan-1 increased from 11.1 ± 2.4 ng/mL at ovulation to 12.6 ± 2.3 ng/mL in mid-luteal phase (P = .031) and of heparan sulfate from 663 ± 35 ng/mL to 782 ± 55 ng/mL (P = .011). In contrast to estrogen, there was a detrimental effect of progesterone on the EGX in HUVECs.ConclusionThe relationship between the natural menstrual cycle and the EGX as an indicator of vascular permeability may provide a new explanation for premenstrual edema in healthy women. This may be an attendant phenomenon of a regular physiological process, the hormonal downregulation of the vascular barrier during pregnancy.
      PubDate: 2017-10-11T05:35:33.465889-05:
      DOI: 10.1111/aji.12767
  • 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
  • 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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