A REPRESENTATIVE RAT MODEL OF HUMAN GLY- PHOSATE EXPOSURE AND ITS CONSEQUENCES ON BODY WEIGHT AND REPRODUCTIVE HEALTH

RACCA, ME; GASTIAZORO, MP; CEPEDA, J; DURANDO, M.; MILESI, MM; VARAYOUD, J

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

When evaluating the toxicity of glyphosate-based herbicides (GBHs), variations in the window and length of exposure and ad-ministration routes may influence the effects that are observed. In this sense, prior investigations have demonstrated the impact of glyphosate (Gly) and GBHs on health when exposed during criti-cal developmental periods using different experimental approaches. Nonetheless an evaluation of long-term oral exposure that better mimics the human condition has yet to be conducted. This study aims to investigate whether long-term oral exposure to a safe dose of a GBH alters body weight and reproductive outcomes. Female Wistar rats were fed a control (CON) and GBH supplemented chow-based paste (GBH, 2 mg of Gly/kg bw/day) diets from weaning un-til adulthood (postnatal day (PND)100). Food and tap water were administered ad libitum. Data of body weight and food intake was registered. On PND100, a group was sacrificed and uteri were re-moved for morphometric analysis. The remaining animals were mat-ed and euthanized on gestational day 19. To assess reproductive outcomes, the number of corpora lutea, implantation and resorption sites were determined. Feto-placental parameters were evaluated using data of fetal and placental weight and placental index. Long-term exposure to GBH increased body weight, with no changes in food intake. Endometrial hyperplasia was detected in 100-day-old females exposed to GBH, evidenced by an increased density of uterine glands and stromal nuclei. GBH females had an increase in the rate of pre-implantation embryo losses and a decrease in fetal weight and length. These results suggest long-term oral exposure to GBH induces uterine hyperplasia and affects rat weight, fertility and fetal development. We emphasize the need to deepen the mecha-nisms related to these findings, and to include long-term and oral exposure models for assessing the toxicity of pesticides for being more representative of human exposure.