EXPOSURE TO A GLYPHOSATE-BASED HERBICIDE ALTERS THE GESTATIONAL PROCESS IN WISTAR RATS IN THE LONG TERM

ALARCÓN R.; BIDNER X.; ALEGRE ANA L.; CAGLIERIS, LUZ; MUÑÓZ DE TORO M; LUQUE E; INGARAMO P

Congreso; Reunión Conjunta SAIC SAI SAFIS Noviembre 2022; 2022

It has been demonstrated that neonatal exposure of rats to glyphosate-based herbicides (GBH) alters fertility and uterine decidualization.Rats exposed during early postnatal days to GBH showed, inadulthood, post-implantation failures associated with a diminisheddecidualized area of implantation sites (IS). The present work aimedto investigate the effects of neonatal exposure to GBH on gestationalday 15 (GD15), when placenta development is considered complete.Female Wistar pups received saline solution (control, C) or anenvironmentally relevant dose of 0,2 mg/kg of glyphosate (GBH0,2)or 2 mg/kg of glyphosate (GBH2) by sc injection on postnatal days(PND) 1, 3, 5 and 7. When pups (n=8/group) grew up, on PND90,were mated with fertile males. Pregnant rats were sacrificed onGD15. The IS were counted, and all fetuses and placentas were extracted,measured, and weighted. Two IS of each animal were usedto investigate molecules associated with placental developmentby immunohistochemistry (IHC) or RT-PCR. Length of fetuses andnumber of implantation sites in the GBH0,2 group were decreasedan 8% and 6%, respectively, without changes in placental weight.The protein expression of ER-alpha in decidua basalis decreased(53%) in GBH0,2 without changes in GBH2. The mRNA expressionof iNOS decreased in both groups, 80% in GBH0,2 and 86% inGBH2. The mRNA expression of TNF-alpha also was lower in bothgroups: 58% in GBH0,2 and 53% in GBH2. Present results demonstratethat neonatal exposure to GBH interferes with the molecularpathway involved in decidualization and placental developmentshowing more deleterious effects at the lower dose. DecreasedTNF-alpha and iNOS would interfere with the relaxation of vascularsmooth muscle impairing angiogenesis in early gestation. Deregulationof the studied molecules and ER-alpha expression duringembryo development might explain reproductive failures observedin neonatal GBH-exposed rats.