Different effects by sex on hypothalamic-pituitary axis of prepubertal offspring rats produced by in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP)

Abstract

This study investigated the effect of pre and perinatal exposure to di-(2-ethylhexyl) phthalate (DEHP) on the neuroendocrine parameters that regulate reproduction in prepubertal male and female rats. DEHP at doses of 3 and 30 mg/kg. bw/day was administered orally in the drinking water to dam rats since pregnancy onset until the moment of pups sacrifice at 15 days of age. In these animals gonadotropin serum level and the hypothalamic contents of the amino acids aspartate, glutamate and gamma-aminobutyric acid were determined. No changes in gonadotropin levels and amino acid neurotransmitters were detected at the low dose in both sexes. However, DEHP administered at high dose (30 mg/kg bw/day) to dams produced a significant decrease in the inhibitory neurotransmitter GABA and an increase in the stimulatory neurotransmitter aspartate in prepubertal male offspring rats. These modifications were accompanied by gonadotropin serum levels increase. On the contrary, in treated female rats this chemical increased both, aspartate and GABA, which exert a characteristic stimulatory action on gonadotropin in 15-day-old normal females. This study provides new data about changes produced by DEHP on the hypothalamic amino acid neurotransmitters involved in the neuroendocrine reproductive regulation, in prepubertal male and female rat offspring from dams exposed during gestational and lactational periods. These alterations induced by DEHP exposure could be related to the gonadotropin modifications also described in this work, and with changes in the production of sexual hormones previously reported by other authors.