Chronic exposure to a glyphosate-based herbicide alters the expression of key molecules involved in hypothalamic regulation of the rat oestrous cycle

ROSSETTI MF,; VARAYOUD JG,; STOKER C.; GASTIAZORO MP,; CANESINI G.; SCHUMACHER R; RAMOS JG.

Congreso; XXXV Annual Meeting Argentine Society for Research in Neurosciences.; 2020

SAN

Glyphosate-based herbicides (GBHs) are extensively used and it has been reported that they may act as endocrine disruptors. Activation of steroid receptors in specific hypothalamic regions like the anteroventral periventricular nucleus (AvPv) and the arcuate nucleus (Arc) is necessary for ovulation and a normal oestrous cycle. This study aimed to describe the effects of chronic exposure to GBH during adult life, at levels close to the reference dose, on the hypothalamic regulation of the oestrous cycle. Adult rats were exposed for 3 months to 2 mg/kg/day of GBH through their diet (GBH Group-GG; Control Group-CG with saline solution). mRNA expression of Kisspeptin (Kiss) was evaluated in brain nuclei isolated by micropunch. GBH rats showed a lower percentage of time in proestrus-oestrous stages when compared to controls. Immunohistochemistry for oestrogen receptor alpha (ERα) and progesterone receptor (PR) showed changes in expression in AvPv, Arc and medial preoptic nuclei (Mpo) in rats exposed to GBH, the same as for REA and SMTR (ERα co-regulators). Kiss mRNA results showed significantly lower expression in the Mpo of the GG. These results suggest that a dose of GBH considered safe alters the rat´s cyclicity and modifies expression of key brain molecules involved in its regulation. Therefore, these changes may provide new evidence of the possible effects of glyphosate on fertility at hypothalamic level.