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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 (4 g/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 developmentalmore » 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. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.« less

Authors:
; ; ; ; ;  [1];  [1];  [2]
  1. Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China)
  2. (China)
Publication Date:
OSTI Identifier:
22687769
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 288; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADRENAL GLANDS; CHOLESTEROL; CORTICOSTERONE; CYTOCHROMES; ECOLOGICAL CONCENTRATION; ELECTRONS; EOSIN; ETHANOL; GROWTH FACTORS; HEMATOXYLIN; INSULIN; METABOLIC ACTIVATION; MINERALOCORTICOIDS; OXIDOREDUCTASES; PHOSPHOTRANSFERASES; RATS; RECEPTORS; TRANSMISSION ELECTRON MICROSCOPY

Citation Formats

Huang, Hegui, He, Zheng, Zhu, Chunyan, Liu, Lian, Kou, Hao, Shen, Lang, Wang, Hui, E-mail: wanghui19@whu.edu.cn, and Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.07.005.
Huang, Hegui, He, Zheng, Zhu, Chunyan, Liu, Lian, Kou, Hao, Shen, Lang, Wang, Hui, E-mail: wanghui19@whu.edu.cn, & Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071. Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms. United States. doi:10.1016/J.TAAP.2015.07.005.
Huang, Hegui, He, Zheng, Zhu, Chunyan, Liu, Lian, Kou, Hao, Shen, Lang, Wang, Hui, E-mail: wanghui19@whu.edu.cn, and Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071. Thu . "Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms". United States. doi:10.1016/J.TAAP.2015.07.005.
@article{osti_22687769,
title = {Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms},
author = {Huang, Hegui and He, Zheng and Zhu, Chunyan and Liu, Lian and Kou, Hao and Shen, Lang and Wang, Hui, E-mail: wanghui19@whu.edu.cn and Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071},
abstractNote = {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 (4 g/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. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.},
doi = {10.1016/J.TAAP.2015.07.005},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 288,
place = {United States},
year = {2015},
month = {10}
}