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

PACINI, GUILLERMINA; LORENZ, VIRGINIA; VARAYOUD, JORGELINA; LUQUE, ENRIQUE HUGO; MILESI, MARÍA MERCEDES

Buenos aires

Congreso; Reunión conjunta de Sociedades de Biociencias - Sociedad Argentina de Investigación en Clínica (SAIC) - LXII Reunión Anual; 2017

SAIC, SAIB, SAI, SAFE, SAH, SAP, SAB, SAFIS, SAA

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, we found 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 whether these alterations might be induced by a defective uterine functional differentiation during the pre-implantation period. Pregnant rats (F0) were orally exposed to Gly or a GBH through food, in a dose of 2 mg of glyphosate/kg/day (RfD, EPA), from gestational day (GD) 9 until weaning (lactational day 21). Sexually mature F1 females were pregnant and uterine samples collected on GD5 (pre-implantation period) for morphological and mRNA analysis. Uterine sections were stained with hematoxylin and eosin to analyze the following morphological features: luminal epithelial height, number of glands, and thickness of myometrium and subephitelial stroma. The expression of implantation-associated genes, such as progesterone receptor (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-treated rats. These results are in accordance with the lower expression of LIF in both groups, since it is mainly secreted by glands. A downregulation of PR was found in glyphosate-treated rats, which correlated with a lower expression of Hoxa10 detected in both exposed groups. In conclusion, perinatal exposure to Gly or GBH induced uterine 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 results also suggested that the active principle, glyphosate, is the responsible of the observed effects.