Acute uterine effects and long-term reproductive alterations in postnatally exposed female rats to a mixture of commercial formulations of endosulfan and glyphosate

Abstract

Endosulfan and glyphosate are widely used pesticides and have been associated to reproductive disorders. We examine the acute and long-term effects of postnatal exposure to commercial formulations of endosulfan (EF), glyphosate (glyphosate-based herbicide, GBH) and a mixture of both pesticides (MIX). After birth, female pups of Wistar rats received saline solution (CONTROL), EF (600 μg/kg of b.w/day), GBH (2 mg/kg of b.w/day) or a mixture (at the same doses) from postnatal day (PND) 1 to PND7. The uterine histology and expression of Hoxa10, estrogen (ERα) and progesterone (PR) receptors were evaluated on PND8. Reproductive performance was evaluated on gestational day 19. GBH and MIX rats showed an increment of 1) the incidence of luminal epithelial hyperplasia, 2) PR and Hoxa10 expression. EF modified ERα and Hoxa10 expression. During adulthood, MIX and GBH rats showed higher post-implantation losses while EF alone produced an increase of pre-implantation losses. We showed that the co-administration of both pesticides produced acute uterine effects and long–term deleterious reproductive effects that were similar to those induced by GBH alone. We consider important to highlight the necessity to evaluate the commercial pesticide mixture as a more representative model of human exposure to a high number of pesticides.