Perinatal exposure to glyphosate or a glyphosate-based formulation disrupts hormonal and uterine milieu during the receptive state in rats

PACINI, GUILLERMINA; LORENZ, VIRGINIA; CADAVIZ, DALMA B.; VARAYOUD, JORGELINA; MILESI, MARÍA M.

Buenos Aires (Modalidad Virtual)

Simposio; International Symposium on Reproductive Health: overcoming barriers for research in reproduction; 2021

Centro de Estudios Farmacológicos y Botánicos (CEFyBO) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)

Glyphosate (Gly) is the active ingredient of all glyphosate-based herbicides (GBHs), which are the most widely applied herbicides worldwide. Nowadays, the safety of Gly and its formulations remains to be a controversial issue. We showed that a GBH formulation administered during gestation and lactation induces subfertility in F1 female rats due to a decrease in embryo implantation. Here, we sought to investigate the effects of perinatal exposure to a GBH or Gly on female fertility, and the hormonal and uterine milieu during the preimplantation period. F0 pregnant rats orally received a GBH or Gly in a dose of 2 mg of glyphosate/kg/day from gestational day (GD) 9 until weaning. F1 females were evaluated to determine the reproductive performance on GD19; and the sex steroid serum levels, the expression of estrogen receptor alpha (ERa), progesterone receptor (PR) and implantation-related genes on GD5 (preimplantation period). GBH and Gly induced preimplantation losses in F1 rats. GBH and Gly groups exhibited higher 17ß-estradiol serum levels (Control: 21.40 ± 2.61 pg/mL; GBH: 30.41 ± 0.93 pg/mL; Gly: 30.41 ± 0.61 pg/mL) without changes in progesterone. Both compounds increased the uterine ERa protein expression: while GBH induced a significant increase in ERa expression in the subepithelial stroma, Gly did in the gland compartment. No differences were detected for ERa at mRNA level between the experimental groups; and only Gly decreased PR mRNA expression. Also, GBH and Gly downregulated Hoxa10 (*p < 0.05) and Lif (*p < 0.05) genes, with no difference in Muc1 and Areg expression. To conclude, perinatal exposure to a GBH or Gly disrupted critical hormonal and uterine molecular targets during the receptive state, possibly associated with the implantation failures. Overall, similar results were found in GBH- and Gly-exposed rats, suggesting that the active principle might be the main responsible for the deleterious effects.