Gestational Hypoxia Induces Sex-differential Methylation of Crhr1 Linked to Anxiety-like Behavior

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2013 Mar 27

PMID 23529784

Citations 19

Authors

Xi Wang

Fan-Sen Meng

Zong-Yun Liu

Jun-Ming Fan

Ke Hao

Xue-Qun Chen

Ji-Zeng Du

Affiliations

Soon will be listed here.

Abstract

Stress during gestation increases vulnerability to disease and changes behavior in offspring. We previously reported that hypoxia and restraint during pregnancy sensitized the hypothalamic-pituitary-adrenal (HPA) axis and induced anxiety-like behavior in the adult offspring. Here, we report that gestational intermittent hypoxia (GIH) elicited a sex-dependent anxiety-like behavior in male P90 offspring and activation of corticotropin-releasing hormone (CRH) and CRH type-1 receptor (CRHR1) mRNA in the hypothalamic paraventricular nucleus (PVN) and in male E19 hypothalamus. These linked to demethylation at several specific sites of CpG island of Crhr1 promoter in P90 PVN and E19 embryo hypothalamus in GIH groups. Crhr1 DNA demethylation is more crucial in CpG island 1 than island 2 for activation of CRHR1 mRNA. DNMT3b is required for the Crhr1 DNA methylation than DNMT1 and DNMT3a in increased CRHR1 mRNA. We first address a novel hypothesis that GIH-induced male-sex-dependent demethylation at CpG sites of Crhr1 DNA in promoter triggers elevation of CRHR1 mRNA in PVN and anxiety-like behavior in adult offspring.

Citing Articles

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CRHR1 mediates the transcriptional expression of pituitary hormones and their receptors under hypoxia.

Wang T, Xia F, Gong J, Xu X, Lv M, Chatoo M Front Endocrinol (Lausanne). 2022; 13:893238.

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