GLYPHOSATE-BASED HERBICIDE DISRUPTS ANGIOGENESIS IN THE RAT UTERUS

CAGLIERIS, LUZ; INGARAMO P. I.; MUÑOZ-DE-TORO M; ALARCÓN R.; LUQUE E

Congreso; Reunión Anual de la sociedad Argentina de Investigación Clínica; 2019

Abstract/Resumen: It has been demonstrated that neonatalexposure of rats to glyphosate-based herbicides (GBH) alters theuterine development and fertility. Rats neonatally exposed duringpostnatal days to GBH shows post-implantation failuresassociated with diminished decidualized area of implantationsites (IS). The aim of the present work was to investigate theeffects of neonatal exposure to GBH on angiogenesis in the ratuterus. Female Wistar pups received saline solution (control, C)or an environmentally relevant dose of GBH (2 mg/kg) by scinjection on postnatal day (PND) 1, 3, 5 and 7. Pups (n=8/group) were sacrificed on PND8 to evaluate angiogenesisimmediately after the end of treatment. On PND90, other groupof females were mated with fertile males and pregnant rats weresacrificed on gestation day 9 (GD9) to investigate genesassociated with angiogenesis in the IS. The uterine angiogenesiswas assessed on PND8 by IHC expression of VEGF. The mRNAexpression of iNOS, Notch1, COX2 and angiopoietin-2 (Ang-2)genes were assayed by RT-PCR in uterine samples on PND8 or inIS on GD9. On PND8, angiogenesis measure by VEGF increasedin luminal epithelium (2 vs. 26 %) and stromal compartment (9vs. 17 %) of GBH rats. On PND8, the uterine mRNA expression ofboth iNOS (83 vs. 54 %) and Notch1 (19 vs. 13 %) diminished inGBH rats. On IS of GBH-exposed group diminished the mRNAexpression of Notch1 (21 vs. 12 %), COX2 (19 vs. 5 %), andiNOS (47 vs. 20 %). While, the mRNA expression of Ang-2increased (28 vs. 62 %) on IS of GBH rats. Present resultsdemonstrate that the neonatal exposure to GBH interferes withthe molecular pathway responsible of vascular adaptation duringuterine development and decidualization process. Dysregulationof the studied molecules occurs early in GBH exposed rats andremains long even when pregnant rats begins embryoimplantation. Altered angiogenesis during embryo implantationmight explain reproductive failures found in neonatal GBHexposed rats.