Effects of Neonatal Resveratrol Exposure on Adult Male and Female Reproductive Physiology and Behavior

Abstract

Resveratrol (RES) is a phytoestrogen that has the ability to bind to estrogen receptors (ERs) and evoke biological effects that parallel those exerted by endogenous and synthetic estrogens. We have shown in previous studies that adult female rats acutely exposed to RES exhibit estrous cycle irregularity, ovarian hypertrophy, and alterations in sociosexual behavior. The present experiment characterizes the prolonged effects of maternal RES exposure throughout the lactational period on subsequent behavior, reproductive tissues, and brain morphology of the adult offspring. During adulthood, female offspring exposed to RES throughout nursing exhibited reduced body weight and increased ovarian weight, but exhibited normal estrous cyclicity and sociosexual behavior, without changes in the volume of the sexually dimorphic nucleus of the preoptic area or the anteroventral periventricular nucleus of the hypothalamus. During adulthood, males exposed to RES throughout nursing exhibited decreased body weight and plasma testosterone concentration, increased testicular weight, and reduced sociosexual behavior. These males also had significantly smaller sexually dimorphic nucleus of the preoptic area volumes and larger anteroventral periventricular nucleus volumes compared to male controls. These data suggest that postnatal exposure to RES may affect estrogenic activity in specific peripheral tissues (e.g., the gonads), while inducing antiestrogenic effects in the brain. Thus, the present study supports recent in vitro and in vivo findings that RES differs from most other phytoestrogens by acting as a possible mixed ER agonist/antagonist, depending on the tissue-specific availability of ER subtypes that are preferentially localized in specific brain regions and throughout the reproductive tract. More importantly these data indicate that maternal consumption of phytoestrogens during lactation can have lasting effects on the offspring that may not become apparent until they reach adulthood.