A REPRESENTATIVE RAT MODEL OF HUMAN GLYPHOSATE EXPOSURE AND ITS CONSEQUENCES ON BODY WEIGHT AND REPRODUCTIVE HEALTH

RACCA, MARÍA EMILIA; GASTIAZORO, MARÍA PAULA; DURANDO, MILENA; MILESI, MARÍA MERCEDES; VARAYOUD, JORGELINA; CEPEDA, JULIETA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias.; 2023

When evaluating the toxicity of glyphosate-based herbicides (GBHs), variations in the window and length of exposure and administration 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 critical 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 doseof a GBH alters body weight and reproductive outcomes. Female Wistar rats were fed a control (CON) and GBH supplemented chowbased paste (GBH, 2 mg of Gly/kg bw/day) diets from weaning until 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 removed for morphometric analysis. The remaining animals were mated 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. Longterm 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 mechanisms 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.