Effects of perinatal exposure to a glyphosate based herbicide on the mammary gland of pre and postpubertal male rats

GOMEZ AL; ALTAMIRANO GA; DELCONTE MB; MASAT E; OSTI MR; LUQUE EH; MUÑOZ-DE-TORO M; KASS L

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

Glyphosate exposure during critical periods of development induced adverse effects on the reproductive system of male rats, suggesting an endocrine disruption action. In addition, it has been reported that the male rat mammary gland (MG) is affected by the action of endocrine disruptors. Here, we evaluated whether perinatal exposure to a glyphosate based herbicide (GBH) modifies the MG development of pre and postpubertal male animals. Pregnant rats (F0) were exposed orally through the diet to vehicle (C, saline solution) or 350 mg/kg/day of GBH from gestational day 9 until weaning. On postnatal day 21 (PND21) and PND60 F1 males were sacrificed and MG and blood samples were collected. The MG samples were processed for whole mount (WM) or kept at -80°C for RT-PCR analysis. On PND21 and PND60 serum levels of testosterone (T) were measured and WMs were analyzed. On PND60, the mRNA expression of estrogen receptor alpha (ESR1) and androgen receptor (AR) was also evaluated. The treatment with GBH produced no signs of abnormal maternal or nursing behaviors, or changes in the body weight gain or pellet consumption of the F0 dams. The length of gestation was unaltered, and no gross malformations were observed in the F1 pups at delivery or weaning. No differences were observed in T serum levels between experimental groups and T concentration was higher on PND60 (C: 1.93±0.43 ng/ml; GBH: 1.83±0.60 ng/ml) compared to PND21 (C: 0.27±0.06; GBH: 0.27±0.12 ng/ml). On PND21, the treatment with GBH reduced MG total area. In contrast, on PND60, total area, longitudinal growth and perimeter were increased in GBH-exposed group; no differences were observed in the epithelial area. In addition, GBH treatment decreased the mRNA expression of ESR1 on PND60 animals, whereas AR mRNA levels were increased. Our results demonstrate that perinatal exposure to GBH alters MG morphology and gene expression long after exposure ended and suggest that the effects may be due to endocrine disruption.