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

Gestational hypoxia induced anxiety-like behaviors in newborn male rats.

“Another prenatal stressor, gestational hypoxia (GIH), induced anxiety-like behaviors in newborn male rats.”

Decreased expression of DNMT3B in the PVN persisted into adulthood in 90-d-old male GIH rats.

“The decreased expression of DNMT3B in the PVN persisted into adulthood in 90-d-old male GIH rats (Wang et al., 2013).”

Hypomethylation of Crhr1 initiated in utero persists even after birth into adulthood.

“suggesting that the hypomethylation of Crhr1 initiated in utero persists even after birth into adulthood (Wang et al., 2013).”

In both 19-d-old male embryos and 90-d-old male GIH offspring, hypomethylation of CpG islands within the Crhr1 promoter was observed.

“In both 19-d-old male embryos and 90-d-old male GIH offspring, hypomethylation of CpG islands within the Crhr1 promoter were observed, suggesting that the hypomethylation of Crhr1 initiated in utero persists even after birth into adulthood (Wang et al., 2013).”

Dnmt1 and Dnmt3a were unaltered in male and female GIH embryos.

“Wang et al. (2013) reported that while Dnmt1 and Dnmt3a were unaltered in male and female GIH embryos, contrary to aforementioned anxiety studies (though different stress paradigms and brain regions were used), DNMT3B was downregulated in male embryos and upregulated in female embryos, possibly explaining the methylation differences of Crhr1 in male and female offspring.”

The CRH/Crf studies of Wang et al. (2013) and Elliott et al. (2010) show a direct correlation between Dnmt3b levels and CRF-associated genes in the PVN, suggesting that in this brain region Dnmt3b may be responsible for modulating their expression via methylation.

“The CRH/Crf studies of both Wang et al. (2013) and Elliott et al. (2010) show a direct correlation between Dnmt3b levels and CRF-associated genes in the PVN, suggesting that in this brain region, Dnmt3b may be responsible for modulating their expression via methylation.”

In the hypothalamic PVN, an increase in CRH and CRHR1 was observed in male GIH offspring, but not females.

“In the hypothalamic PVN, an increase in CRH and CRHR1 (a CRH receptor gene) was observed in male offspring, but not females, suggesting a sex-related positive stress adaptation in female animals (Wang et al., 2013).”

The sex difference in CRH and CRHR1 increase suggests a sex-related positive stress adaptation in female animals.

“suggesting a sex-related positive stress adaptation in female animals (Wang et al., 2013).”

The DNMT3B expression differences possibly explain the methylation differences of Crhr1 in male and female offspring.

“possibly explaining the methylation differences of Crhr1 in male and female offspring.”

DNMT3B was downregulated in male GIH embryos and upregulated in female GIH embryos.

“DNMT3B was downregulated in male embryos and upregulated in female embryos, possibly explaining the methylation differences of Crhr1 in male and female offspring.”