PERINATAL EXPOSURE TO GLYPHOSATE OR A COMMERCIAL FORMULATION DISRUPTS THE WINDOW OF UTERINE RECEPTIVITY REDUCING THE IMPLANTATION SITES IN RATS.

GUILLERMINA PACINI ; MARÍA R. REPETTI; JORGELINA VARAYOUD ; VIRGINIA LORENZ; LUISINA D. DEMONTE; MARÍA MERCEDES MILESI; DALMA B CADAVIZ; ENRIQUE H LUQUE

Congreso; Reunión Conjunta SAIC-SAI -SAFIS; 2018

Glyphosate is the active principle of the most globally used herbicides. The toxicity of commercial formulations (glyphosate-based herbicides, GBHs) vs. glyphosate alone is a matter of intense debate. Present study investigates the effects of perinatal exposure to glyphosate (Gly) or a GBH on female reproductive performance. Pregnant rats (F0) were exposed to Gly or a GBH through food, in a dose of 2 mg of glyphosate/kg/day, from gestational day (GD) 9 until weaning (lactational day (LD) 21). Glyphosate levels were measured in the serum of F0 dams during gestation and lactation by UHPLC?MS/MS. When F1 females reached the sexual maturity, they were bred and submitted to a fertility test to evaluate the pregnancy rate, and on GD19, the number of corpora lutea and the implantation and resorption sites. Other pregnant control or exposed females were sacrificed on GD5 to assess the hormonal and molecular milieu during the preimplantation period by determining: the serum levels of 17β-estradiol (E2) by radioimmunoassay, and in uterine samples, the protein expression of estrogen receptor alpha (ERα) and Ki67 proliferation marker by immunohistochemistry. Glyphosate serum concentrations in F0 dams were similar over the treatment period, and levels reached were 13.4 ± 2.3 ug/L and 38.7 ± 5.6 ug/L for Gly and GBH groups, respectively. Perinatal exposure of F1 female rats to Gly or GBH induced subfertility. The pregnancy rate was not affected, but we detected a decreased number of implantation sites. Moreover, both treatments increased the serum levels of E2 (Control: 21.4 ± 2.6 pg/ml; Gly: 30.4 ± 0.6 pg/ml; GBH: 30.4 ± 0.9 pg/ ml) at the preimplantation period, which was associated with higher uterine ERα expression and cell proliferation. We propose that estrogenic-proliferative alterations might disrupt the window of uterine receptivity, reducing the number of implantation sites.