GLYPHOSATE-BASED HERBICIDE DISRUPTS ANGIOGENESIS IN THE RAT UTERUS

INGARAMO PI; ALARCÓN R; CAGLIERIS ML; VARAYOUD J; MUÑOZ-DE-TORO M; LUQUE EH

Congreso; Reunión Anual de Sociedades de Biociencia 2019; 2019

It has been demonstrated that neonatal exposure of rats toglyphosate-based herbicides (GBH) alters the uterine development and fertility. Rats neonatally exposed during postnatal days to GBHshows post-implantation failures associated with diminished decidualized area of implantation sites (IS). The aim of the present work was to investigate the effects of neonatal exposure to GBH on angiogenesis in the rat uterus. Female Wistar pups received saline solution (control, C) or an environmentally relevant dose of GBH (2 mg/kg) by sc injection on postnatal day (PND) 1, 3, 5 and 7. Pups (n= 8/group) were sacrificed on PND8 to evaluate angiogenesis immediately after the end of treatment. On PND90, other group of females were mated with fertile males and pregnant rats were sacrificed on gestation day 9 (GD9) to investigate genes associated with angiogenesis in the IS. The uterine angiogenesis was assessed on PND8 by IHC expression of VEGF. The mRNA expression of iNOS, Notch1, COX2 and angiopoietin-2 (Ang-2) genes were assayed by RT-PCR in uterine samples on PND8 or in IS on GD9. On PND8, angiogenesis measure by VEGF increased in luminal epithelium (2 vs. 26 %) and stromal compartment (9 vs. 17 %) of GBH rats. OnPND8, the uterine mRNA expression of both iNOS (83 vs. 54 %) and Notch1 (19 vs. 13 %) diminished in GBH rats. On IS of GBH-exposed group diminished the mRNA expression of Notch1 (21 vs. 12 %), COX2 (19 vs. 5 %), and iNOS (47 vs. 20 %). While, the mRNA expression of Ang-2 increased (28 vs. 62 %) on IS of GBH rats. Present results demonstrate that the neonatal exposure to GBH interferes with the molecular pathway responsible of vascular adaptation during uterine development and decidualization process. Dysregulation of the studied molecules occurs early in GBH exposed rats and remains long even when pregnant rats begins embryo implantation. Altered angiogenesis during embryo implantation might explain reproductive failures found in neonatal GBH-exposed rats.