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

RAMIRO ALARCÓN; PAOLA I. INGARAMO ; ENRIQUE H. LUQUE; MA. MERCEDES MILESI ,; MÓNICA M. MUÑOZ-DE-TORO; JORGELINA G. VARAYOUD

Congreso; Reunión Conjunta de Biociencias.; 2017

The glyphosate-based herbicides (GBH) are commonly used to control weeds. Recently, ithas been shown that neonatal treatment of Wistar rats with GBH alters the uterinedevelopment. These rats have reproductive problems as post-implantation failure associatedwith diminished decidualized area of implantation sites (IS). The aim of present work was toevaluate if decidualization failure in GBH-exposed rats could be caused by defective uterineangiogenesis. Female Wistar pups received saline solution (control, C) or an environmentallyrelevant dose of GBH (2 mg/kg) by sc. injection on postnatal day (PND) 1, 3, 5 and 7. OnPND90 females 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 newlyformed blood vessels were detected by nestin immunostaining. The mRNA expression ofVEGF and NOTCH1 were quantified using qRT-PCR. Macrophages were detected byimmunohistochemistry and the results were expressed as volume density. GBH-exposed ratsshowed 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 GBHexposed rats (C: 2.9±0.5% vs GBH: 1.6±0.3%, p˂0.05). Furthermore, the mRNA expressionof two angiogenic regulators 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 resultsdemonstrate that the neonatal exposure to GBH interferes with the mechanism involved invascular adaptation during decidualization process. The recruitment of macrophages couldevidence an inflammatory process linked to decreased angiogenesis during decidualizationthat might be responsible for the reproductive failures found in neonatal GBH-exposed rats.