Implantation failure caused by uterine glandular dysfunction in rats exposed to glyphosate or a commercial glyphosate-based formulation.

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

Simposio; International Symposium on Reproductive Health; 2021

 Embryo implantation is a complex process that requiresthe temporal interaction between developmentally competent blastocysts andareceptive uterus.Estradiol serum levels and/or uterine estrogenreceptor alpha (ERα) expression are known to be crucial in determining thereceptivity window and the success of implantation.Our previous resultsshowed thatin utero and lactationalexposure toa glyphosate based herbicide (GBH) or its active principle,glyphosate (Gly), impairsfemale fertility by reducing the number of implantedembryos and increasing the rate of pre-implantation embryo losses. Inthe present work we sought to investigatewhether implantation failures in Glyand GBH exposed females are related to alterations in estradiol serumconcentrations, levels of uterine ERα expression and/or cellular events thatunder that the control of estrogens during the receptive stage. Pregnant rats(F0) were exposed to Gly or GBH through food, in a dose of 2 mg ofglyphosate/kg/day, from gestational day (GD) 9 until weaning. F1 females werepregnant and sacrificed on GD5 (pre-implantation period) to assess: i) theserum levels of 17β-estradiol (E2) by RIA, ii) the uterine expression of ERα byinmmunohistochemistry, iii) the cell proliferation index in the endometrium byKi67 immunostaining, and vi) the expression of cell proliferation-associatedgenes (Fos, Egr1 and Cyclin B1 and D1)by RT-qPCR.Gly and GBH exposed femalesshowed increased serum levels of E2 along with higher protein expression of ERα.Bothcompounds induced an increase in the cell proliferation index in theendometriumbut no changes were detected in the expression of any of theproliferation associated-genes studied. In conclusion, perinatal exposure to Glyor GBH induced hormonal, molecular and cellular long-term alterations that leadto a hiperestrogenicity stage. These alterations may close the window ofuterine receptivity in advance, triggering implantation embryo losses.