Uterine glandular dysfunction in rats exposed to glyphosate or a glyphosate formulation: a possible mechanism of implantation failure

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

Congreso; Reunión Anual de Sociedades de Biociencias 2020; 2020

Glyphosate (Gly) is the active ingredient of multiple herbicide formulationsknown as glyphosate-based herbicides (GBHs), which arethe most globally used pesticides. We have shown that perinatalexposure to either Gly or GBH decreased the number of implantedembryos in female rats. Here, we investigated whether Gly or GBHexposure alter endometrial gland function as a possible mechanismresponsible for implantation failures. Pregnant rats (F0) were exposedto Gly or a GBH through food, in a dose of 2 mg of glyphosate/kg/day, from gestational day (GD) 9 until weaning. F1 females werepregnant and uteri were sampled on GD5 (pre-implantation period)for morphological, immunohistochemical and mRNA analysis. Uterinesections were stained with hematoxylin-eosin to analyze the followingmorphological features: luminal epithelial height, number ofglands, and thickness of myometrium and subepithelial stroma. Wealso determined the expression of molecules that regulate uterinegland function and implantation such as, Forkhead box A2 (FOXA2)and b-catenin which were evaluated by immunohistochemistry, andleukemia inhibitory factor (Lif) that was assessed by qPCR. A lowernumber of uterine glands in Gly (**p<0.01) and GBH (***p<0.001)groups was detected regarding to the control. Both Gly and GBHexposure (*p<0.05 vs control) decreased the expression of Lif. Also,FOXA2 (Gly: **p<0.01; GBH: *p<0.05 vs control) and b-catenin (Glyand GBH: **p<0.01 vs control) expression levels were decreased inthe glandular compartment in both groups. In conclusion, Gly andGBH exposure decreased the number of glands in the pre-implantationuterus, in association with a downregulation of key moleculesfor endometrial gland activity and implantation. These findings suggestthat uterine gland dysfunction might be a mechanism of GlyandGBH-induced implantation failures. Importantly, Gly and GBHinduced similar changes suggesting that both compounds may actthrough similar pathways.