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

ALARCÓN R; BIDNER X; ALEGRE AL; CAGLIERIS ML; MUÑOZ-DE-TORO M; LUQUE EH; INGARAMO PI

Mar del Plata

Congreso; REUNION CONJUNTA SAIC SAI&FAIC SAFIS 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, in adulthood, post-implantation failures associated with a diminished decidualized area of implantation sites (IS). The present work aimed to investigate the effects of neonatal exposure to GBH on gestational day 15 (GD15), when placenta development is considered complete. Female Wistar pups received saline solution (control, C) or an environmentally 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 on GD15. The IS were counted, and all fetuses and placentas were extracted, measured, and weighted. Two IS of each animal were used to investigate molecules associated with placental development by immunohistochemistry (IHC) or RT-PCR. Length of fetuses andnumber of implantation sites in the GBH0,2 group were decreased an 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 expression of iNOS decreased in both groups, 80% in GBH0,2 and 86% in GBH2. The mRNA expression of TNF-alpha also was lower in both groups: 58% in GBH0,2 and 53% in GBH2. Present results demonstrate that neonatal exposure to GBH interferes with the molecular pathway involved in decidualization and placental development showing more deleterious effects at the lower dose. Decreased TNF-alpha and iNOS would interfere with the relaxation of vascular smooth muscle impairing angiogenesis in early gestation. Deregulation of the studied molecules and ER-alpha expression during embryo development might explain reproductive failures observed in neonatal GBH-exposed rats.