Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood

Maternal psychosocial stress during pregnancy alters the epigenetic signature of the glucocorticoid receptor gene promoter in their offspring: a meta-analysis

“…Five of them analyzed maternal anxious-depressive status during pregnancy. [27][28][29][30][31] The remaining 2 papers focused on the effect of maternal exposure to violence (either intimate partner violence or war-related events) during pregnancy. 32,33 As depicted in Figure 2, there is an overlap of 5 analyzed CpG sites (35 to 39) at the promoter of the exon 1 F among 6 of the 7 papers meta-analyzed herein (see also Figure 3 for specific location in the sequence).…”

“…[36][37][38] Nevertheless, meta-analyzed papers which already assessed methylation in these extended regions did not report any correlation between pregnant anxiousdepressive symptomatology and methylation at CpG sites 40-47, thus implying that prenatal stress may not modulate neurobehavior and neuroendocrine response as mediated by NR3C1 methylation. [27][28][29] Prenatal stress-induced methylation changes are thought to partially arise due to increased fetal circulating cortisol levels. Recent evidence points to the essential role of the placental enzyme 11 b-hydroxysteroid dehydrogenase type 2 (11b-HSD2) in regulating the cortisol flux from the mother to the fetus.…”

“…This variability might be biasing the meta-analysis results as each technique has its own limitations. As a matter of fact, both Murgatroyd et al 31 and Hompes et al 29 reported methylation values as for pairs of CpG sites due to the reduced resolution of mass spectrometry analyses thus compromising the comparison. Second, none of the studies explored paired GR expression in association with methylation; therefore, the phenotypic effect of CpG site 36 methylation remains unknown.…”

“…19 Accordingly, the epigenetic modulation caused by anxious-depressive diagnosis during pregnancy seems to impact harder the fetuses when it takes place during the early stages of pregnancy as shown both in animal and human studies. 25,27,29 Thus, the restricted correlations reported by Conradt et al 28 could be due to inclusion of women who experienced either depression or anxiety at any time during pregnancy without specifying the trimester. Fourth, given the length of the NR3C1 promoter area and the preliminary results correlating DNA methylation at additional CpG sites to distinct early stressors, other regions besides exon 1 F could have been investigated.…”

Back to the future: transgenerational transmission of xenobiotic-induced epigenetic remodeling

“…168 Of interest and not surprisingly, the methylation state of the glucocorticoid receptor gene promoter in genomic DNA from cord blood mononuclear cells was significantly associated with maternal anxiety. 169 How stress-initiated epigenetic events in the womb cross-talk with xenobiotic effects at the same level remain to be elucidated.…”