Maternal Care Associated with Methylation of the Estrogen Receptor- 1b Promoter and Estrogen Receptor- Expression in the Medial Preoptic Area of Female Offspring

Variations in maternal behavior are associated with differences in estrogen receptor (ER)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 ER expression in the MPOA and are themselves high LG mothers. In the present studies, cross-fostering confirmed an association between maternal care and ER expression in the MPOA; the biological offspring of low LG mothers fostered at birth to high LG dams show increased ER 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 ER expression is associated with differences in methylation of the relevant ER promoter. Levels of cytosine methylation across the ER 1b 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 ER 1b 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 ER 1b promoter, providing a potential mechanism for the programming of individual differences in ER expression and maternal behavior in the female offspring. (Endocrinology 147: 2909–2915, 2006)