{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T19:21:07Z","timestamp":1787253667971,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471521"],"award-info":[{"award-number":["81471521"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Obstet and Gynaecol"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Intrahepatic cholestasis of pregnancy (ICP) is a specific complication in the middle and late pregnancy and has been recognized as one of the high\u2010risk pregnancy for sudden fetal death. In this study, we aimed to investigate the role of Fas, Caspase\u20108, and Caspase\u20109 pathways in the internal relations of fetal myocardial apoptosis in ICP rat models, thus resulting in fetal intrauterine death. Furthermore, we researched whether ursodeoxycholic acid (UDCA) promoted benefits in fetal cardiomyocyte apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>To establish ICP rat models, on the 15th day of pregnancy, rats were injected 17\u03b1\u2010ethynyl estradiol (EE2). Meanwhile, in experimental group, pregnant rats were treated with EE2\u2009+\u2009UDCA. All rats were sacrificed on the 21st day of pregnancy. The expression levels of Fas, Caspase\u20108, and Caspase\u20109 were examined by western blot and real\u2010time polymerase chain reaction analysis. Fetal rat cardiac tissues were removed and stained for pathological evaluation. In addition, we observed fetal myocardial structure by using transmission electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected high concentrations of bile acids and transaminase in the fetal circulation. And we found increased expression levels of Fas, Caspase\u20108, and Caspase\u20109 proteins and mRNA in the fetal cardiomyocyte in EE2\u2010treated group but not in control\u2010 or EE2\u2009+\u2009UDCA\u2010treated groups. Furthermore, compared to controls, EE2\u2010treated rats exhibited severe fetal myocardial structure damage and the apoptotic bodies by using transmission electron microscopy. UDCA reversed the impairment of fetal cardiomyocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study has led to research into the association between activation of Fas, Caspase\u20108, and Caspase\u20109 pathways and bile acid\u2010induced fetal cardiomyocyte apoptosis, which may be one of the mechanisms on fetal cardiac death in ICP. More importantly, UDCA may improve the adverse outcome of fetus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jog.14765","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T01:03:30Z","timestamp":1618275810000},"page":"2298-2306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Fas, Caspase\u20108, and Caspase\u20109 pathway\u2010mediated bile acid\u2010induced fetal cardiomyocyte apoptosis in intrahepatic cholestasis pregnant rat models"],"prefix":"10.1111","volume":"47","author":[{"given":"Zhaoyi","family":"Song","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Air Force Medical Center, PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Haidian Maternal and Child Health Hospital  Beijing 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