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Prenatal Exposure to Ethanol and the Epigenetic Regulation of Serotonin Transporter ( Slc6a4 ) and Glucocorticoid Receptor ( Nr3c1 ) Genes
Author(s) -
Ngai Ying Fai Tiffany,
Sulistyoningrum Dian C,
Innis Sheila M,
Weinberg Joanne,
Devlin Angela M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.990.20
Subject(s) - endocrinology , medicine , glucocorticoid receptor , serotonin transporter , hypothalamus , offspring , epigenetics , hippocampus , glucocorticoid , biology , dna methylation , gene expression , receptor , serotonin , pregnancy , gene , genetics
Fetal Alcohol Spectrum Disorder (FASD) causes a range of cognitive impairment however the molecular aetiology underlying FASD is not fully understood. We hypothesize that developmental programming of gene expression via epigenetic mechanisms may contribute to FASD. We studied the expression of the glucocorticoid receptor ( Nr3c1 ) and the serotonin transporter ( Slc6a4 ) in the hippocampus and hypothalamus of young adult rats exposed prenatally to ethanol. Female Sprague‐Dawley rats were fed a liquid ethanol diet (E), a pair‐fed liquid control diet (PF), or lab chow (C) throughout pregnancy and the adult offspring were studied at 55 days of age. Female rats from E dams had lower ( P <0.05) Nr3c1 mRNA levels in hippocampus and lower ( P <0.01) Slc6a4 mRNA levels in hypothalamus than female rats from PF dams. Male rats from E dams had higher ( P <0.05) Slc6a4 mRNA levels in hippocampus and lower ( P <0.01) Slc6a4 mRNA levels in hypothalamus than male rats from C dams. Further analysis of the methylation status of 23 CpG sites in the 5′ regulatory region of Slc6a4 in hypothalamus showed lower ( P <0.05) methylation in female and male rats from E dams compared to female and male rats, respectively, from C and PF dams. These findings suggest that prenatal exposure to alcohol may affect the developmental programming of gene expression in hypothalamus via epigenetic mechanisms.

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