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Prenatal caffeine exposure (PCE) caused intrauterine growth retardation (IUGR) and multiple organ dysplasia. This study intended to explore the effect and mechanism of PCE on long bone development in female fetal rats. In vivo, the PCE group pregnant rats were given different concentrations of caffeine during the gestational Day 9\u201020. The mRNA expression of osteogenesis\u2010related genes were significantly reduced in PCE group. In the PCE group (120\u00a0mg\/kg\u00b7d), the length and primary center of fetal femur were shorter, and accompanied by H\u2010type blood vessel abundance reducing. Meanwhile, connective tissue growth factor (CTGF) expression decreased in the growth plate of the PCE group (120\u00a0mg\/kg\u00b7d). In contrast, the miR375 expression increased. In vitro, caffeine decreased CTGF and increased miR375 expression in fetal growth plate chondrocytes. After co\u2010culture with caffeine\u2010treated chondrocytes, the tube formation ability for the H\u2010type endothelial cells was decreased. Furthermore, CTGF overexpression or miR375 inhibitor reversed caffeine\u2010induced reduction of tube formation ability, and miR375 inhibitor reversed caffeine\u2010induced CTGF expression inhibition. In summary, PCE decreased the expression of CTGF by miR375, ultimately resulting in H\u2010type blood vessel\u2010related long bone dysplasia.<\/jats:p>","DOI":"10.1096\/fj.202002230r","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T11:42:16Z","timestamp":1616067736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Prenatal caffeine exposure caused H\u2010type blood vessel\u2010related long bone dysplasia via miR375\/CTGF signaling"],"prefix":"10.1096","volume":"35","author":[{"given":"Hangyuan","family":"He","sequence":"first","affiliation":[{"name":"Department of Joint Surgery and Sports Medicine Zhongnan Hospital of Wuhan University Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanwen","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery Fourth Affiliated Hospital of Guangxi Medical University 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