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Studies have found that prenatal dexamethasone exposure (PDE) decreases sperm quality in male offspring after birth, but the mechanism is unclear. Wistar pregnant rats were subcutaneously injected with 0.1, 0.2, and 0.4\u2009mg\/kg.d dexamethasone at gestational days 9\u201320. The testes and sperm of first-generation (F1) offspring were collected, and F1 offspring were mated with wild-type female rats to obtain F2. Compared with the control group, F1 offspring in PDE group had lower sperm count and motility after birth, and the deformity rate increased. F2 fetal rats\u2019 body length and weight decreased, and the intrauterine growth retardation rate increased. Meanwhile, PDE decreased the expression of connexin 43 (CX43) in offspring testes, whereas T-box transcription factor 2 (TBX2) promoter region histone 3 lysine 9 acetylation (H3K9ac) level and its expression were increased. Traced back to F1 fetus testes, PDE increased the expression of glucocorticoid receptor (GR) and P300, activated GR protein into the nucleus, and made GR act on the TBX2 promoter region. Further, a series of Sertoli cell interventions confirmed that dexamethasone promoted GR to recruit P300, increased the H3K9ac level of TBX2 promoter region and its expression, and inhibited the expression of CX43. This study confirmed that PDE decreased sperm quality of male offspring, which is related to the epigenetic programming of TBX2\/CX43 in the Sertoli cells, provided a theoretical and experimental basis for guiding the rational use of drugs during pregnancy.<\/jats:p>","DOI":"10.1093\/toxsci\/kfad016","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T05:53:51Z","timestamp":1676440431000},"page":"178-193","source":"Crossref","is-referenced-by-count":11,"title":["Epigenetic programming of TBX2\/CX43 mediates lower sperm quality in male offspring induced by prenatal dexamethasone exposure"],"prefix":"10.1093","volume":"192","author":[{"given":"Yi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Wuhan University , Wuhan 430071, China"},{"name":"Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University , Wuhan 430071, China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease , Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Wuhan University , Wuhan 430071, China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease , Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Renmin Hospital of Wuhan University , Wuhan 430060, China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease , Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9599-4786","authenticated-orcid":false,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Wuhan University , Wuhan 430071, China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease , Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"2023041718433170500_","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.fertnstert.2019.12.028","article-title":"MicroRNAs in combined spent culture media and sperm are associated with embryo quality and pregnancy outcome","volume":"113","author":"Abu-Halima","year":"2020","journal-title":"Fertil. 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