{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:09:49Z","timestamp":1792174189867,"version":"4.4.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9]]},"abstract":"\n We previously showed that prenatal caffeine exposure (PCE) induces intrauterine growth retardation (IUGR) and high susceptibility to nonalcoholic fatty liver disease in offspring rats, and the underlying mechanisms are associated with fetal overexposure to maternal glucocorticoids. Herein, we aimed to verify whether PCE disrupts liver development before and after birth and explore its possible programming mechanism.\n In vivo<\/jats:italic>\n , reduced fetal weights and increased IUGR rates were accompanied by fetal liver developmental dysfunction in PCE rats. Increased fetal serum corticosterone and decreased insulin-like growth factor 1 (IGF1) levels were observed. Both male and female fetal livers exhibited increased glucocorticoid function-related gene (\n Gr<\/jats:italic>\n \/\n C<\/jats:italic>\n \/\n ebp\u03b1<\/jats:italic>\n ) expression and inhibited IGF1 signaling pathway (\n Igf1<\/jats:italic>\n \/\n Igf1r<\/jats:italic>\n \/\n Akt2<\/jats:italic>\n ) expression. At PW6, the levels of serum corticosterone and glucocorticoid function-related genes in PCE offspring livers were decreased, while serum IGF1 and liver IGF1 signaling pathway expression were increased, accompanied by obvious catch-up growth and enhanced liver function. Furthermore, in PCE adult offspring under chronic stress, serum corticosterone and liver\n Gr<\/jats:italic>\n \/\n C<\/jats:italic>\n \/\n ebp\u03b1<\/jats:italic>\n expression levels were elevated, while the serum IGF1 and liver IGF1 signaling pathway levels were decreased.\n In vitro<\/jats:italic>\n , cortisol (not caffeine) upregulated\n GR<\/jats:italic>\n and\n C\/EBP\u03b1<\/jats:italic>\n expression and downregulated\n IGF1R<\/jats:italic>\n expression. The\n IGF1R<\/jats:italic>\n expression downregulated by cortisol was partially reversed by GR or C\/EBP\u03b1 knockdown. In conclusion, PCE-induced liver developmental dysfunction in fetal rats and catch-up growth in IUGR offspring. The mechanisms may be closely associated with GR\/C\/EBP\u03b1 upregulation and IGF1\/IGF1R signaling pathway downregulation in the fetal liver, caused by intrauterine programming of the liver glucocorticoid\u2013IGF1 axis induced by glucocorticoid overexposure.\n <\/jats:p>","DOI":"10.1530\/joe-19-0066","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T15:16:07Z","timestamp":1563981367000},"page":"211-226","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":34,"title":["Prenatal caffeine exposure induces liver developmental dysfunction in offspring rats"],"prefix":"10.1530","volume":"242","author":[{"given":"Bo","family":"He","sequence":"first","affiliation":[{"name":"1Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, China"},{"name":"2School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinxian","family":"Wen","sequence":"additional","affiliation":[{"name":"3Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China"},{"name":"4Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwei","family":"Hu","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Hu","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Magdalou","sequence":"additional","affiliation":[{"name":"5UMR 7561 CNRS-Universit\u00e9 de Lorraine, Facult\u00e9 de M\u00e9dicine, Vandoeuvre-l\u00e8s-Nancy, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liaobin","family":"Chen","sequence":"additional","affiliation":[{"name":"3Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China"},{"name":"4Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, China"},{"name":"4Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/242\/3\/JOE-19-0066.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/242\/3\/JOE-19-0066.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:44Z","timestamp":1784555804000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/242\/3\/211-226\/5159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/joe-19-0066","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9]]}}}