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

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

Buenos Aires

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2017

Sociedad Argentina de Investigación Clínica (SAIC)

The glyphosate-basedherbicides (GBH) are commonly used to control weeds. Recently, it has beenshown that neonatal treatment of Wistar rats with GBH alters the uterinedevelopment. These rats have reproductive problems as post-implantation failureassociated with diminished decidualized area of implantation sites (IS). Theaim of present work was to evaluate if decidualization failure in GBH-exposedrats could be caused by defective uterine angiogenesis. Female Wistar pupsreceived saline solution (control, C) or an environmentally relevant dose ofGBH (2 mg/kg) by sc. injection on postnatal day (PND) 1, 3, 5 and 7. On PND90females were mated with fertile males non-exposed to GBH. Pregnant rats weresacrificed on gestation day 9 (GD9) to evaluate angiogenesis process in the IS.The newly formed blood vessels were detected by nestin immunostaining. The mRNAexpression of VEGF and NOTCH1 were quantified using qRT-PCR. Macrophages weredetected by immunohistochemistry and the results were expressed as volumedensity. 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% vsGBH: 1.6±0.3%, p˂0.05). Furthermore, the mRNA expression of two angiogenicregulators VEGF and NOTCH1 was decreased 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 demonstratethat the neonatal exposure to GBH interferes with the mechanism involved invascular adaptation during decidualization process. The recruitment ofmacrophages could evidence an inflammatory process linked to decreasedangiogenesis during decidualization that might be responsible for thereproductive failures found in neonatal GBH-exposed rats.