Perinatal exposure to glyphosate or its commercial formulations: uterine molecular mechanisms involved in embryo implantation failures

PACINI G; LORENZ V; VARAYOUD J; LUQUE EH; MILESI MM

Buenos Aires

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2017

Sociedad Argentina de Investigación Clínica (SAIC)

Glyphosate is the active ingredient in a widevariety of broad-spectrum non-selective herbicides. Commercial formulations ofglyphosate include other compounds which act as adjuvants. Recently, we foundthat perinatal exposure to either glyphosate (Gly) or a glyphosate-basedherbicide (GBH) caused subfertility in female rats associated with implantationfailures. In this work, we studied whether these alterations might be inducedby a defective uterine functional differentiation during the pre-implantationperiod. Pregnant rats (F0) were orally exposed to Gly or a GBH through food, ina dose of 2 mg of glyphosate/kg/day (RfD, EPA), from gestational day (GD) 9until weaning (lactational day 21). Sexually mature F1 females were pregnant and uterine samples collected onGD5 (pre-implantation period) for morphological andmRNA analysis. Uterine sections were stained with hematoxylin and eosin to analyzethe following morphological features: luminal epithelial height, number ofglands, and thickness of myometrium and subephitelial stroma. The expression ofimplantation-associated genes, such as progesterone receptor (PR), the homeoboxHoxa10 and leukemia inhibitory factor (LIF), was assessed by RT-qPCR. At themorphological level, a lower number of uterine glands was detected in Gly- andGBH-treated rats. These results are in accordance with the lower expression of LIFin both groups, since it is mainly secreted by glands. A downregulation of PR was found in glyphosate-treatedrats, which correlated with a lower expression of Hoxa10 detected in bothexposed groups. In conclusion, perinatal exposure to Gly or GBH induced uterine morphological and molecularalterations during the pre-implantation period, which might explain, at leastin part, the implantationfailures triggered by Gly and GBH treatments. These results also suggestedthat the active principle, glyphosate, is the responsible of the observedeffects.    Keywords: Glyphosate, Uterus, Subfertility, Implantation