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

MA. MERCEDES MILESI; VIRGINIA LORENZ; ENRIQUE H. LUQUE; GUILLERMINA PACINI; JORGELINA G. VARAYOUD

Congreso; Reunión Conjunta de Biociencias.; 2017

Glyphosate is the active ingredient in a wide variety of broad-spectrum non-selective herbicides. Commercial formulations of glyphosate include other compounds which act as adjuvants. Recently, wefound that perinatal exposure to either glyphosate (Gly) or a glyphosate-based herbicide (GBH) caused subfertility in female rats associated with implantation failures. In this work, we studied whetherthese alterations might be induced by a defective uterine functionaldifferentiation during the pre-implantation period. Pregnant rats (F0)were orally exposed to Gly or a GBH through food, in a dose of2 mg of glyphosate/kg/day (RfD, EPA), from gestational day (GD)9 until weaning (lactational day 21). Sexually mature F1 femaleswere pregnant and uterine samples collected on GD5 (pre-implantation period) for morphological and mRNA analysis. Uterine sectionswere stained with hematoxylin and eosin to analyze the followingmorphological features: luminal epithelial height, number of glands,and thickness of myometrium and subephitelial stroma. The expression of implantation-associated genes, such as progesteronereceptor (PR), the homeobox Hoxa10 and leukemia inhibitory factor(LIF), was assessed by RT-qPCR. At the morphological level, a lower number of uterine glands was detected in Gly- and GBH-treatedrats. These results are in accordance with the lower expression ofLIF in both groups, since it is mainly secreted by glands. A downregulation of PR was found in glyphosate-treated rats, which correlatedwith a decreased expression of Hoxa10 detected in both exposedgroups. In conclusion, perinatal exposure to Gly or GBH induceduterine morphological and molecular alterations during the pre-implantation period, which might explain, at least in part, the implantation failures triggered by Gly and GBH treatments. These resultsalso suggested that the active principle, glyphosate, is the responsible of the observed effects.