Environmental regulation of the neural epigenome

AbstractParental effects are a major source of phenotypic plasticity. Moreover, there is evidence from studies with a wide range of species that the relevant parental signals are influenced by the quality of the parental environment. The link between the quality of the environment and the nature of the parental signal is consistent with the idea that parental effects, whether direct or indirect, might serve to influence the phenotype of the offspring in a manner that is consistent with the prevailing environmental demands. In this review we explore recent studies from the field of ‘environmental epigenetics’ that suggest that (1) DNA methylation states are far more variable than once thought and that, at least within specific regions of the genome, there is evidence for both demethylation and remethylation in post-mitotic cells and (2) that such remodeling of DNA methylation can occur in response to environmentally-driven, intracellular signaling pathways. Thus, studies of variation in mother–offspring interactions in rodents suggest that parental signals operate during pre- and/or post-natal life to influence the DNA methylation state at specific regions of the genome leading to sustained changes in gene expression and function. We suggest that DNA methylation is a candidate mechanism for parental effects on phenotypic variation

Maternal Programming of Sexual Behavior and Hypothalamic-Pituitary-Gonadal Function in the Female Rat

Variations in parental care predict the age of puberty, sexual activity in adolescence and the age at first pregnancy in humans. These findings parallel descriptions of maternal effects on phenotypic variation in reproductive function in other species. Despite the prevalence of such reports, little is known about potential biological mechanisms and this especially true for effects on female reproductive development. We examined the hypothesis that parental care might alter hypothalamic-pituitary-ovarian function and thus reproductive function in the female offspring of rat mothers that vary pup licking/grooming (LG) over the first week postpartum. As adults, the female offspring of Low LG mothers showed 1) increased sexual receptivity; 2) increased plasma levels of luteinizing hormone (LH) and progesterone at proestrus; 3) an increased positive-feedback effect of estradiol on both plasma LH levels and gonadotropin releasing-hormone (GnRH) expression in the medial preoptic region; and 4) increased estrogen receptor α (ERα) expression in the anterioventral paraventricular nucleus, a system that regulates GnRH. The results of a cross-fostering study provide evidence for a direct effect of postnatal maternal care as well as a possible prenatal influence. Indeed, we found evidence for increased fetal testosterone levels at embryonic day 20 in the female fetuses of High compared to Low LG mothers. Finally, the female offspring of Low LG mothers showed accelerated puberty compared to those of High LG mothers. These data suggest maternal effects in the rat on the development of neuroendocrine systems that regulate female sexual behaviour. Together with studies revealing a maternal effect on the maternal behavior of the female offspring, these findings suggest that maternal care can program alternative reproductive phenotypes in the rat through regionally-specific effects on ERα expression

Mating behavior of the female offspring and the effect of cross-fostering.

<p>(a) Tested with a stud male in a small traditional testing arena, the mean (±SEM) lordosis rating in the adult female offspring of High LG mothers was lower compared to Low and Mid offspring (n = 10–12/group).* p<0.05. (b) Tested in a pacing chamber, the mean (±SEM) lordosis rating of adult female offspring of High LG mothers was lower compared to Low female offspring. * p<0.05. The inter-intromission interval showed no significant differences (n = 12/group). (c) Mean±SEM lordosis rating or inter-intromission interval in the adult female offspring of Low or High LG mothers fostered to and reared by Low (Low-Low; High-Low) or High (Low-High; High-High) tested with a stud male in the pacing chamber (n = 7–13/group). Groups lying underneath the line differ significantly (<i>p</i> <0.05) from the Low-Low group. (d) Mean±SEM testosterone level in amniotic fluid of embryonic day 20 female offspring of High or Low LG mothers (n = 20–25 pups from 12–14 litters/group; *p<.01).</p