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Submitted on September 1, 2005
Accepted on February 23, 2006
Douglas Hospital Research Center, 6875 LaSalle Blvd, Montréal, Québec H4H 1R3, Canada. McGill Program for the Study of Behaviour, Genes and Environment.Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montréal, Québec H3G 1Y6, Canada
* To whom correspondence should be addressed. E-mail: michael.meaney{at}mcgill.ca.
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 Stat5 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 programing of individual differences in ER expression and maternal behavior in the female offspring.
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