Shakti Sharma | PubMed Health

PubMed2004

Epigenetic programming by maternal behavior.

Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.

Acetylation↗

PubMed2003

Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area.

Lactating rats exhibit stable individual differences in pup licking/grooming (LG) over the first week postpartum. Such naturally occurring variations in maternal behavior are associated with differences in estrogen-inducible oxytocin receptors in the medial preoptic area (MPOA) of the hypothalamus. We compared levels of ER alpha and ER beta mRNA in the MPOA of lactating High or Low LG mothers as well as in their nonlactating, female offspring, which inherit the maternal phenotype of their mothers. Among lactating females, High LG females exhibited significantly elevated levels of ER alpha mRNA compared with Low LG females. Likewise, the adult, virgin female offspring of High LG mothers showed higher levels of ER alpha mRNA in the MPOA compared with those of Low LG mothers. There were no group differences in levels of ER beta mRNA. Differences in ER alpha protein expression in the MPOA were confirmed using Western blot analysis. To further characterize the effects of estrogen in the MPOA, cFos immunoreactivity was compared in ovariectomized, adult offspring of High and Low LG dams treated with estradiol or oil. Increased cFos activity in the anterior ventral nucleus of the MPOA was observed in estradiol-treated High LG, but not Low LG females. These findings suggest that natural variations in maternal care are associated with differences in ER alpha expression in the MPOA and that such differences are transmitted from the mother to her female offspring.

Animals↗