GLYPHOSATE-BASED HERBICIDE ALTERS DECIDUAL ANGIOGENESIS IN NEONATALLY EXPOSED RATS

ALARCÓN, RAMIRO; CAGLIERIS, MARÍA LUZ; MUÑOZ-DE-TORO, MÓNICA; LUQUE, ENRIQUE HUGO; INGARAMO PAOLA INÉS

Workshop; International Symposium on Reproductive Health; 2021

Glyphosate-based herbicides (GBH) are the most employed agrochemicals around the globe. Although has been considered harmless for decades, growing evidence shows that GBHs might have adverse effects on human and animal health. In previous studies, we showed that female rats neonatally exposed to GBH exhibited, at prepuberal age,altered expression of molecules involved in uterine development with higher incidence of luminal epithelial hyperplasia andincreased cell proliferation. In addition, we reported a reduction of the implantation sites (IS) sizeand altered expression of decidualization-related moleculesin association with increased post-implantation lossesrates. Considering that decidualization comprises not only morphogenetic and biochemical but also vascular changes, our aim was to evaluate the effects of neonatal GBH exposure in angiogenesis on post-natal day (PND) 8 and on gestational day (GD)9 (post-implantation period). To achieve this, Wistar female rats were s.c.exposed to saline solution (vehicle; n=16) or to GBH (2 mg glyphosate/kg-bw/day; n=16) every 48h from PND1 to PND7. On PND8, eight animals from each group were euthanized, and uterine samples were collected. On PND90, the remaining animals were mated. In the morning of GD9, pregnant rats were sacrificed, and IS were collected. Histology was evaluated by H-E, while immunohistochemistry was performed to determine the VEGF, Nestin and Ki67 expression. Angiogenic-related molecules were also assessed by RT-PCR. On PND8,VEGF, Notch1, iNOS and Angpt2 mRNA levels were decreasedin GBH group. On GD9, the vascular area and vessel diameter,cell proliferation, VEGF and Nestinprotein expression,and VEGF, Notch1, iNOS and COX2 gene expressionweredownregulated in exposed animals. In conclusion, neonatal exposure to a GBH alters the expression of molecules involved in angiogenesis during uterine development at prepubertal ageand during the decidual angiogenic process. These alterations might contribute to the increased post-implantation losses observed in GBH exposed rats.