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

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

Modalidad virtual

Simposio; International Symposium on Reproductive Health; 2021

Glyphosate-based herbicides (GBHs) are the most widely applied pesticides in the world. Glyphosate (Gly), the active ingredient of all GBHs, is combined with other chemicals known as co-formulants to enhance herbicide action. Little is known about the contribution of co-formulants to the toxicity of herbicides. In addition, evidence is not conclusive whether the adverse effects are caused by Gly or GBH. Recently we have shown that perinatal exposure to either Gly or GBH decreased the number of implanted embryos in rats. In the present work, we sought toinvestigate whether implantation failures in Gly and GBH exposed female rats are related to alterations in endometrial gland function. Pregnant rats (F0) were exposed to Gly or GBH through food, in a dose of 2 mg of glyphosate/kg/day, from gestational day (GD) 9 until weaning. Sexually mature F1 females became pregnant and were euthanized on GD5 (pre-implantation period) to assess the number of glands in uterine samples and the expression of molecules that regulate uterine gland function and implantation such as, leukemia inhibitory factor (Lif) assessed by qPCR, and Forkhead box A2 (FOXA2) and b-catenin evaluated by immunohistochemistry. A lower number of uterine glands in Gly and GBH-exposed groups was detected in relation to the control. Both Gly and GBH exposure decreased the expression of Lif. Also, FOXA2 and b-catenin expression levels were downregulated in the glandular compartment in both exposed groups. In conclusion, perinatal exposure to Gly or GBH decreased the number of glands in the preimplantation uterus and downregulated molecules with key roles for endometrial gland activity and implantation. These morphological and molecular alterations suggest that uterine gland dysfunction might be a mechanism of Glyand GBH-induced implantation failures. Importantly, Gly and GBH induced similar changes suggesting that both compounds may act through similar pathways.