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This study aimed to elucidate the intrauterine programming mechanisms of adult hypercholesterolemia. The results showed that prenatal nicotine exposure (PNE) caused intrauterine growth retardation and hypercholesterolemia in male adult offspring rats. Hepatic cholesterol synthesis and output were deceased\n                    <jats:italic>in utero<\/jats:italic>\n                    but increased in adults; hepatic reverse cholesterol transport (RCT) persistently deceased before and after birth. Meanwhile, PNE elevated serum corticosterone level and decreased hepatic IGF1 pathway activity in male fetuses, whereas converse changes were observed in male adults. The chronic stress model and cortisol\u2010treated HepG2 cells verified that excessive glucocorticoid (GC)\u2010induced GC\u2010IGF1 axis programming enhanced hepatic cholesterol synthesis and output. In addition, PNE decreased the expression of specific protein 1 and P300 enrichment and H3K27 acetylation at the promoter region of genes responsible for RCT both in fetal and adult, male livers and reduced expression of those genes, similar alterations were also confirmed in cortisol\u2010treated HepG2 cells, suggesting that excessive GC\u2010related programming induced continuous RCT reduction by epigenetic modification. Taken together, the \u201c2\u2010programming\u201d approach discussed above may ultimately contribute to the development of hypercholesterolemia in male adult offspring.\u2014Zhou, J., Zhu, C., Luo, H., Shen, L., Gong, J., Wu, Y., Magdalou, J., Chen, L., Guo, Y., Wang, H. Two intrauterine programming mechanisms of adult hypercholesterolemia induced by prenatal nicotine exposure in male offspring rats. FASEB J. 33, 1110\u20131123 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201800172r","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T13:55:01Z","timestamp":1534427701000},"page":"1110-1123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Two intrauterine programming mechanisms of adult hypercholesterolemia induced by prenatal nicotine exposure in male offspring rats"],"prefix":"10.1096","volume":"33","author":[{"given":"Jin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwen","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Zhongnan Hospital Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Magdalou","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche (UMR) 7561 Centre National de la Recherche Scientifique (CNRS) Nancy Universit\u00e9  Vandoeuvre\u2010l\u00e8s\u2010Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liaobin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Zhongnan Hospital Wuhan University  Wuhan China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Wuhan University  Wuhan China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Wuhan University  Wuhan China"},{"name":"Hubei Provincial Key Laboratory of Developmentally Originated Disease  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000196306.42418.0e"},{"key":"e_1_2_9_3_1","first-page":"25","article-title":"Resistant hypercholesteremia in clinical practice: new insight into the causes and methods of treatment [in Russian]","volume":"331","author":"Kuchmin A. 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