LONG-TERM EFFECTS OF NEONATAL EXPOSURE TO ENVIRONMENTAL RELEVANT DOSE OF GLYPHOSATE-BASED HERBICIDE ON UTERINE DECIDUALIZATION

INGARAMO P; VARAYOUD J; MILESI,MM; GUERRERO SCHIMPF M; MUÑOZ-DE-TORO M; LUQUE EH

Congreso; SAIC 2016; 2016

In Argentina, glyphosate-based herbicides (GBH) are commonly used to control weeds. Although regulatory agencies have asserted that are relatively safe, reports from our laboratory suggest that GBH may have endocrine disrupting effects. The aim of present work was to evaluate the long-term effects of neonatal exposure to a GBH assessing parameters related to uterine decidualization in rats. Female Wistar pups received saline solution (control, C) or an environmental relevant dose of GBH (2 mg/kg) by sc injection on postnatal day (PND) 1, 3, 5 and 7. On PND90 female rats were mated with fertile non-exposed male. Pregnant rats were sacrificed on gestation day (GD) 19 and GD9 to evaluate molecular markers in the implantation sites (IS). Desmin immunostaining was used as a marker of decidualization. The newly formed blood vessels were detected by nestin immunostaining. The Wnt5a, Wn7a and β-catenin expressions were evaluated in IS for their key roles on decidualization. On GD19, GBH group showed a high incidence of fetal resorptions. On GD9, a significant decrease in the decidualized area (DA) (C: 1.55±0.32 mm2 vs GBH: 0.71±0.18 mm2, p˂0.05) linked to a decreased caliber of newly formed vessels was found at the IS of the GBH group (C: 0.06±0.01 µm vs GBH: 0.04±0.01 µm, p˂0.05). Moreover, Wnt5a expression decreased on antimesometrial zone of IS of GBH group (C: 7.12±0.66 vs GBH: 4.88±0.43, p˂0.05) and Wnt7a expression was downregulated in luminal epithelium of mesometrial zone (C: 10.32±1.86 vs GBH: 3.46±1.57, p˂0.05). No changes were observed in β-catenin expression between the groups. Long-term effect of neonatal exposure to GBH was evidenced by an increased incidence of abortion associated with altered decidualization process. A decreased DA associated with impaired blood supply in GBH exposed rats may be due to an altered Wnts activation pathway. These mechanisms may be responsible for the high incidence of abortion in GBH treated rats.