{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:14:20Z","timestamp":1762899260844},"reference-count":42,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"\n Context:<\/jats:title>\n Microbial invasion of the amniotic fluid (AF) cavity stimulates an inflammatory response that involves activin-A, a pleiotropic mediator member of the TGF\u03b2 superfamily involved in connective tissue remodeling. The role of AF follistatin, a natural inhibitor of activin-A, in inflammation-induced preterm birth (PTB), has yet to be determined.<\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n The objective of the study was to investigate the relationships between AF activin-A and follistatin in physiological gestation and in pregnancies complicated by PTB and to evaluate a possible role played by the activin-A-follistatin balance in processes leading to PTB and preterm premature rupture of membranes (PPROM).<\/jats:p>\n <\/jats:sec>\n \n Study Design:<\/jats:title>\n The AF levels of total activin-A and follistatin were immunoassayed in 168 women with a normal pregnancy outcome or PTB with and without intraamniotic inflammation or PPROM. The impact of the activin-A-follistatin imbalance on PTB terminal effector pathways (prostaglandins [prostaglandin E2, prostaglandin F2\u03b1] and matrix metalloproteinases [MMP-1, MMP-2, MMP-3, and MMP-9]) was investigated in an amniochorion explant system challenged with lipopolysaccharide (LPS) to mimic inflammation.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n AF follistatin and the activin-A to follistatin ratio varied with gestational age, both decreasing toward term (P &lt; .001). Activin-A was up-regulated in AF infection (&gt;2-fold elevation in activin-A to follistatin ratio) correlating directly with severity of inflammation (both P &lt; .001). Activin-A increased prostaglandins, MMP-1, and MMP-9 released by amniochorion (P &lt; .05) to LPS-equivalent levels. Follistatin effectively blunted the prostaglandin response to activin-A and LPS and that of MMPs after activin-A but not after LPS challenge.<\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Activin-A and follistatin are part of the complex inflammatory response of the gestational sac to infection and modulate effector pathways leading to PTB. The activin-A to follistatin ratio may play a role in determining the clinical phenotype of PTB as preterm labor or PPROM.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/jc.2015-4147","type":"journal-article","created":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T17:36:28Z","timestamp":1462815388000},"page":"2785-2793","source":"Crossref","is-referenced-by-count":16,"title":["Imbalance of Amniotic Fluid Activin-A and Follistatin in Intraamniotic Infection, Inflammation, and Preterm Birth"],"prefix":"10.1210","volume":"101","author":[{"given":"John T.","family":"Hardy","sequence":"first","affiliation":[{"name":"Department of Obstetrics\/Gynecology and Reproductive Sciences (J.T.H., M.E.M., C.A.L., L.L.S.), Yale University School of Medicine, New Haven, Connecticut 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina A.","family":"Buhimschi","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research (I.A.B., G.Z.), Columbus, Ohio 43215"},{"name":"The Research Institute at Nationwide Children's Hospital, and Department of Pediatrics (I.A.B.), The Ohio State University College of Medicine, Columbus, Ohio 43215"},{"name":"Department of Obstetrics\/Gynecology (I.A.B., C.S.B.), The Ohio State University College of Medicine, Columbus, Ohio 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan E.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology and Reproductive Sciences (J.T.H., M.E.M., C.A.L., L.L.S.), Yale University School of Medicine, New Haven, Connecticut 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guomao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research (I.A.B., G.Z.), Columbus, Ohio 43215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine A.","family":"Laky","sequence":"additional","affiliation":[{"name":"Department of 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