GLYPHOSATE-BASED HERBICIDE ALTERS DECIDUAL ANGIOGENESIS IN NEONATALLY EXPOSED RATS

ALARCON, RAMIRO; CAGLIERIS, LUZ; MUÑOZ-DE-TORO M; LUQUE, ENRIQUE H.; INGARAMO P. I.

Simposio; International Symposium on Reproductive Health: overcoming barriers for research in reproduction; 2021

ISRH

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 and increased cell proliferation. In addition, we reported a reduction of the implantation sites (IS) size and altered expression of decidualization-related molecules in association with increased post-implantation losses rates. 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 decreased in GBH group. On GD9, the vascular area and vessel diameter, cell proliferation, VEGF and Nestin protein expression, and VEGF, Notch1, iNOS and COX2 gene expression were downregulated in exposed animals. In conclusion, neonatal exposure to a GBH alters the expression of molecules involved in angiogenesis during uterine development at prepubertal age and during the decidual angiogenic process. These alterations might contribute to the increased post-implantation losses observed in GBH exposed rats.