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

PACINI G; LORENZ V; CADAVIZ DB; VARAYOUD J; MILESI MM

Simposio; International Symposium on Reproductive Health; 2021

Glyphosate (Gly) is the active ingredient of all glyphosate-basedherbicides (GBHs), which are the most widely applied herbicides worldwide. Nowadays,the safety of Gly and its formulations remains to be a controversial issue. Weshowed that a GBH formulation administered during gestation and lactationinduces subfertility in F1 female rats due to a decrease in embryoimplantation. Here, we sought to investigate the effects of perinatal exposureto a GBH or Gly on female fertility, and the hormonal and uterine milieu duringthe preimplantation period. F0 pregnant rats orally received a GBH or Gly in adose of 2 mg of glyphosate/kg/day from gestational day (GD) 9 until weaning. F1females were evaluated to determine the reproductive performance on GD19; andthe sex steroid serum levels, the expression of estrogen receptor alpha (ERα),progesterone receptor (PR) and implantation-related genes on GD5(preimplantation period). Gly, similar to results of the commercial formulationinduced preimplantation losses in F1 rats. GBH and Gly groups exhibited higher17β-estradiol(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 serum levels on GD5. All animals showed an increaseof uterine ERαprotein expression: GBH animals in the subepithelialstroma, and Gly in glands.. No differences were detected on ERαat mRNA level.; and only Gly decreased PR mRNA expression. Also, GBH and Gly downregulatedHoxa10 and Lif  genes, withno difference in Muc1 and Areg expression (SI PONÉS LOS p iríanen todos los resultados….. To conclude, perinatal exposure to a GBH or Glydisrupted critical hormonal and uterine molecular targets during the receptivestate, possibly associated with the implantation failures. Overall, similarresults were found in GBH- and Gly-exposed rats, suggesting that the activeprinciple might be the main responsible for the deleterious effects.