NEONATAL EXPOSURE TO A GLYPHOSATE-BASED HERBICIDE DISRUPTS ANGIOGENESIS IN UTERINE DECIDUALIZATION IN PREGNANT RATS

INGARAMO P. I.; VARAYOUD J; MILESI M.; ALARCON, RAMIRO; MUÑOZ-DE-TORO M; LUQUE EH

Santa Fe

Congreso; Reunion conjunta de sociedades de biociencias; 2017

SAIC-SAIB-SAI-SAA-SAB-SAFE-SAFIS-SAH-SAP

The glyphosate-based herbicides (GBH) are commonly used tocontrol weeds. Recently, it has been shown that neonatal treatmentof Wistar rats with GBH alters the uterine development. These ratshave reproductive problems as post-implantation failure associatedwith diminished decidualized area of implantation sites (IS). The aim of present work was to evaluate if decidualization failure inGBH-exposed rats could be caused by defective uterine angiogenesis.Female Wistar pups received saline solution (control, C) or anenvironmentally relevant dose of GBH (2 mg/kg) by sc. injection onpostnatal day (PND) 1, 3, 5 and 7. On PND90 females were matedwith fertile males non-exposed to GBH. Pregnant rats were sacrificedon gestation day 9 (GD9) to evaluate angiogenesis process inthe IS. The newly formed blood vessels were detected by nestin immunostaining.The mRNA expression of VEGF and NOTCH1 werequantified using qRT-PCR. Macrophages were detected by immunohistochemistryand 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 VEGFand 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 demonstrate that the neonatal exposure to GBH interferes with the mechanism involved in vascular adaptation during decidualization process. The recruitment of macrophages could evidence an inflammatory process linked to decreased angiogenesisduring decidualization that might be responsible for the reproductivefailures found in neonatal GBH-exposed rats.