Maternal Care Associated with Methylation of the Estrogen Receptor-α1b Promoter and Estrogen Receptor-α Expression in the Medial Preoptic Area of Female Offspring

McGill University, Montréal, Quebec, Canada
Endocrinology (Impact Factor: 4.5). 07/2006; 147(6):2909-15. DOI: 10.1210/en.2005-1119
Source: PubMed


Variations in maternal behavior are associated with differences in estrogen receptor (ER)-alpha expression in the medial preoptic area (MPOA) and are transmitted across generations such that, as adults, the female offspring of mothers that exhibit increased pup licking/grooming (LG) over the first week postpartum (i.e. high LG mothers) show increased ERalpha expression in the MPOA and are themselves high LG mothers. In the present studies, cross-fostering confirmed an association between maternal care and ERalpha expression in the MPOA; the biological offspring of low LG mothers fostered at birth to high LG dams show increased ERalpha expression in the MPOA. Cross-fostering the biological offspring of high LG mothers to low LG dams produces the opposite effect. We examined whether the maternal programing of ERalpha expression is associated with differences in methylation of the relevant ERalpha promoter. Levels of cytosine methylation across the ERalpha1b promoter were significantly elevated in the adult offspring of low, compared with high, LG mothers. Differentially methylated regions included a signal transducer and activator of transcription (Stat)5 binding site and the results of chromatin immunoprecipitation assays revealed decreased Stat5b binding to the ERalpha1b promoter in the adult offspring of low, compared with high, LG mothers. Finally, we found increased Stat5b levels in the MPOA of neonates reared by high, compared with low, LG mothers. These findings suggest that maternal care is associated with cytosine methylation of the ERalpha1b promoter, providing a potential mechanism for the programming of individual differences in ERalpha expression and maternal behavior in the female offspring.

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    • "y profiles that par - allel those of the mother ( Champagne , Weaver , Diorio , Sharma , & Meaney , 2003 ) . Cross - fostering and methylation studies have elu - cidated that these intergenerational links are contingent on the epigenetic regulation of gene expression , modulated by the quality of maternal care during the offspring ' s early life ( Champagne et al . , 2006 ; Kundakovic & Champagne , 2014 ) . Similar epigenetic pathways ( arrow ⑧ ) have been found to guide the development of the HPA ( Weaver et al . , 2004 ) , VP ( Veenema , 2012 ) , DA ( Peña , Neugut , Calarco , & Champagne , 2014 ) , and BDNF systems ( Roth & Sweatt , 2011 ) , whose reciprocal interactions with the OT system ( arrow ⑨ )"
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