Dietary influence on the impact of ethinylestradiol-induced alterations in the endocrine/reproductive system with perinatal maternal exposure

Abstract

We investigated the effects of two diets, differing in phytoestrogen contents, on the phenotypic changes induced in the endocrine/reproductive system by perinatal exposure to an estrogen agonist during a critical period for brain sexual differentiation in rats. Ethinylestradiol (EE) was mixed at a concentration of 0.5 ppm into two diets: CRF-1, a standard rodent diet containing soybean-derived phytoestrogens; and a soy-free (SF) diet. These diets were provided to maternal Sprague–Dawley rats during gestational day 15 to postnatal day 10. Growth suppression of offspring was evident with EE especially during the exposure period and was slightly enhanced with the SF diet. On the other hand, most of the female offspring exposed to EE with CRF-1 showed early onset of vaginal opening, strong irregularity in estrous cycle (persistent estrus) and profound histopathological alterations, such as multifollicular ovaries, endometrial hypertrophy, and diffuse hyperplasia of the anterior pituitary. These EE-induced changes were much less pronounced with the SF diet. The results thus demonstrated differential effects of perinatal EE depending on the basal diet used, with enhancement of typical estrogenic responses in females by potential soybean-derived factor(s).