title: Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms.
abstract: Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a "two-programming" mechanism for PEE-induced adrenal developmental toxicity: "the first programming" is a lower functional programming of adrenal steroidogenesis, and "the second programming" is GC-metabolic activation system-related GC-IGF1 axis programming.
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Hegui
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Kou
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000014:Abnormalities, Drug-Induced / Q000097:blood / Q000209:etiology* / Q000235:genetics; D000311:Adrenal Glands / Q000002:abnormalities* / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001835:Body Weight; D049109:Cell Proliferation; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D000431:Ethanol; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D020567:Fetal Weight; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar; D012737:Sex Factors; D015398:Signal Transduction; D015430:Weight Gain; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D019394:Ki-67 Antigen; D010750:Phosphoproteins; C548904:insulin-like growth factor-1, rat; D000098682:Steroidogenic Acute Regulatory Protein; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D015096:3-Hydroxysteroid Dehydrogenases; D003345:Corticosterone
keywords: Adrenal steroidogenesis; Glucocorticoid-metabolic system; Glucocorticoid–insulin-like growth factor 1 axis; Intrauterine growth retardation; Intrauterine programming; Prenatal ethanol exposure