Ethanol-induced inhibition of fetal hypothalamic–pituitary–adrenal axis due to prenatal overexposure to maternal glucocorticoid in mice

Autor: Jiang Zheng, Hui Wang, Gai Liang, Xiao liang Pan, Man Chen
Rok vydání: 2011
Předmět:
Male
Hypothalamo-Hypophyseal System
endocrine system
medicine.medical_specialty
Placenta
Pituitary-Adrenal System
Mice
Inbred Strains
Biology
Toxicology
Pathology and Forensic Medicine
Fetal Development
Mice
chemistry.chemical_compound
Fetus
Pregnancy
Corticosterone
11-beta-Hydroxysteroid Dehydrogenase Type 2
Internal medicine
medicine
Animals
Cholesterol Side-Chain Cleavage Enzyme
RNA
Messenger
Fetal Growth Retardation
Ethanol
Steroidogenic acute regulatory protein
Cholesterol side-chain cleavage enzyme
Body Weight
Central Nervous System Depressants
Gene Expression Regulation
Developmental
Membrane Transport Proteins
Fetal Body Weight
Cell Biology
General Medicine
medicine.disease
Specific Pathogen-Free Organisms
Endocrinology
medicine.anatomical_structure
Fetal Weight
chemistry
Maternal Exposure
Female
Glucocorticoid
Hypothalamic–pituitary–adrenal axis
medicine.drug
Zdroj: Experimental and Toxicologic Pathology. 63:607-611
ISSN: 0940-2993
DOI: 10.1016/j.etp.2010.04.015
Popis: 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.
Databáze: OpenAIRE
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