CONICET | Buscador de Institutos y Recursos Humanos

Glyphosate exposure during critical periods of development induced adverse effects on the reproductive system of male rats, suggesting an endocrine disruption action. In addition, we have shown that the male rat mammary gland is susceptible to endocrine disruption. Here, we evaluated whether perinatal exposure to a glyphosate based herbicide (GBH) alters the mammary gland morphology and endocrine response in postpubertalmale animals. Pregnant rats were exposed orally through the diet to vehicle (saline solution), 350 or 3.5 mg/kg/day of GBH from gestational day 9 until weaning. On postnatal day 60, the male offspring were sacrificed and mammarygland and blood samples were collected. Testosterone (T) and estradiol (E) serum levels were measured and, total area, perimeter, longitudinal growth and mammary density were analyzed in mammary gland whole-mounts (WMs). Relative epithelial area, estrogen (ESR1) and androgen receptor (AR) protein expression and proliferation index were also evaluated in histological sections. T and E serum levels were similar between groups; however, the exposure to GBH350 increased the longitudinal growth and reduced the mammary density, without modifying the total area or perimeter of the mammary gland. In accordance with these results, the proliferation index, relativeepithelial area and ESR1 expression were also reduced in GBH350-exposed animals, whereas no difference was detected in AR expression. On the other hand, GBH3.5-exposed animals presented similar WM and histological parameters to controls rats. Also, in this last group, ESR1 expression was decreased and AR levels were increased, without altering the proliferation index. Our results demonstrate that perinatal exposure to GBH alters the morphology of the malerat mammary gland long after exposure ended and suggest that the effects may bedue to an altered ESR1 expression.