Neonatal exposure to a glyphosate-based herbicide disrupts angiogenesis in uterine decidualization in pregnant rats

INGARAMO P; VARAYOUD J; MILESI MM; ALARCÓN R; MUÑOZ DE TORO M; LUQUE EH

Congreso; Reunión conjunta de sociedades de Biociencias; 2017

The glyphosate-based herbicides (GBH) are commonly used to control weeds. Recently, it has been shown that neonatal treatment of Wistar rats with GBH alters the uterine development. These rats have reproductive problems as post-implantation failure associated with diminished decidualized area of implantation sites (IS). The aim of present work was to evaluate if decidualization failure in GBH-exposed rats could be caused by defective uterine angiogenesis. 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. On PND90 females were mated with fertile males non-exposed to GBH. Pregnant rats were sacrificed on gestation day 9 (GD9) to evaluate angiogenesis process in the IS. The newly formed blood vessels were detected by nestin immunostaining. The mRNA expression of VEGF and NOTCH1 were quantified using qRT-PCR. Macrophages were detected by immunohistochemistry and the results were expressed as volume density.GBH-exposed rats showed an increase of macrophages in the decidua, specifically in the antimesometrial zone (C: 1.2±0.1% vs GBH: 1.7±0.2%, p˂0.05). In addition, nestin positive area decreased in GBH-exposed rats (C: 2.9±0.5% vs GBH: 1.6±0.3%, p˂0.05). Furthermore, the mRNA expression of two angiogenic regulators VEGF and NOTCH1 wasdecreased in GBH-exposed rats (C: 55±3% vs GBH: 23±5% and C: 21±2% vs GBH: 12±2%, p˂0.05, respectively). Present results demonstrate that the neonatal exposure to GBH disrupts the mechanism involved in vascular adaptation during decidualization process. The recruitment of macrophages could be related with the angiogenic process may be modifying the expression patterns of their secretory products. All these results might be responsible for the reproductive failures found in neonatal GBH-exposed rats.