Ethanol-induced inhibition of fetal hypothalamic-pituitary-adrenal axis due to prenatal overexposure to maternal glucocorticoid in mice.
Prenatal ethanol exposure has been well documented to be one of the etiological factors responsible for intrauterine growth retardation (IUGR). Previous studies have shown that chronic ethanol exposure during pregnancy elevated the basic level of corticosterone in fetus. However, the potential mechanisms behind them are still unclear. The aim of the present study was to investigate the effects of prenatal ethanol exposure on maternal and fetal hypothalamic-pituitary-adrenal (HPA) axis as well as placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), and to clarify the mechanism of ethanol-induced IUGR. Pregnant mice were intragastricly administrated with ethanol at a dose of 6.4 g kg(-1) d(-1) from day 11 to 17 of gestation and parameters representing fetal growth and development were recorded either. The level of corticosterone in maternal serum was determined by ELISA kit. The mRNA expressions of steroidogenic acute regulatory protein (StAR) and cytochrome P450 cholesterol side chain cleavage (P450scc) both in maternal and fetal adrenal, and placental 11β-HSD-2 were detected by real-time quantitative PCR, respectively. The results showed that fetal body weight significantly decreased, and the incidence of IUGR was obviously increased after prenatal ethanol exposure. Maternal serum corticosterone level was elevated, and the expressions of StAR and P450scc were increased in maternal adrenal while decreased in fetal adrenal. The expression of placental 11β-HSD-2 was significantly reduced. These results suggest that prenatal ethanol exposure induces an inhibition of fetal HPA axis activity and IUGR occurs. The mechanism may be associated with ethanol-induced maternal HPA axis activation and high glucocorticoid condition, which impair the placental barrier, and lead to an overexposure of elevated maternal glucocorticoid to fetus, and eventually result in the inhibition of the fetal HPA axis.
Liang
Gai
G
Pharmacology Department of Basic Medical College, Wuhan University, Wuhan 430071, China.
Chen
Man
M
Pan
Xiao-liang
XL
Zheng
Jiang
J
Wang
Hui
H
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005317:Fetal Growth Retardation / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
D002492:Central Nervous System Depressants; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C499209:Stard4 protein, mouse; D000431:Ethanol; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003345:Corticosterone