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However, the pathogenesis and early prevention for PDE offspring prone to cholestatic liver injury have been unclear. In this study, we collected human umbilical cord blood from neonates with prenatal dexamethasone therapy, showing increased primary unconjugated bile acid levels in utero. PDE increased blood primary bile acid levels, enhanced endoplasmic reticulum stress, and led to cholestatic liver injury in adulthood in rats, which is accompanied by the persistent increase of H3K14ac level in cholesterol 27\u03b1\u2010hydroxylase (CYP27A1) promoter and its expression before and after birth. In vitro, dexamethasone activates glucocorticoid receptors, binding to the CYP27A1 promoter, and promotes its transcriptional expression. Through the miR\u2010450b\u20103p\/SIRT1 pathway, it increased the H3K14ac level of the CYP27A1 promoter to enhance its transcription, which continues after birth. Finally, nilvadipine effectively reversed cholestatic liver injury induced by PDE. This study confirmed PDE could cause cholestatic liver injury, and innovatively proposed its early intervention target (CYP27A1) and effective drug (nilvadipine), providing a theoretical and experimental basis for guiding rational drug use during pregnancy, and preventing and treating the fetal\u2010originated cholestatic liver injury.<\/jats:p>","DOI":"10.1002\/mco2.70110","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T21:24:51Z","timestamp":1741728291000},"source":"Crossref","is-referenced-by-count":2,"title":["Cholesterol\u201027\u03b1\u2010hydroxylase inhibitor nilvadipine can effectively treat cholestatic liver injury in adult offspring induced by prenatal dexamethasone exposure"],"prefix":"10.1002","volume":"6","author":[{"given":"Wen","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Pharmacology Wuhan University School of Basic Medical Sciences  Wuhan China"},{"name":"Department of Pharmacy Zhongnan Hospital of Wuhan 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