EXPOSURE TO A GLYPHOSATE-BASED HERBICIDE AFFECTS THE REPRODUCTIVE DEVELOPMENTAL PROGRAMMING WITH LONG-TERM CONSEQUENCES IN A RAT MODEL

LORENZ V; MILESI MM; GUERRERO SCHIMPF ML; GASTIAZORO M.P.; PACINI G; CADAVIZ FERNANDEZ DB; LUQUE EH; VARAYOU J.

Congreso; IFPA 2019 - VIII SLIMP; 2019

Objectives: Glyphosate-based herbicides (GBHs) could produce carcinogenic and endocrine disrupting effects on reproductive organs. Weinvestigate whether postnatal exposure to GBH affects the reproductivedevelopmental programming with long-term effects. We evaluate i)uterine sensitivity to estradiol (E2), ii) estrous cyclicity and steroid levels,and iii) carcinogenic effects in aged rats.Methods: Female pups were injected subcutaneously with saline solution(control) or GBH (2 mg of glyphosate/kg/day, secure dose according to EPA)during the first week of life. To evaluate the sensitivity to E2, rats wereovariectomized and exogenous treated with implants. Morphological andmolecular uterine response to E2 was determined on postnatal day 60.Other animals were used to evaluate the estrous cycle and the steroidserum levels (E2) by RIA and progesterone (P4) by ELISA. Finally, a group ofrats was maintained until 20 months of age. The uteri and vagina wereprocessed for histopathology.Results: GBH-treated rats showed a higher sensitivity to E2 evidenced by1) increased luminal epithelial height, hyperplasia and stromal nucleidensity, 2) increased cellular proliferation and induction of estrogenicgenes. Also, GBH exposure altered estrous cyclicity in association withincreased E2 and decreased P4 serum levels. Furthermore, GBH inducedpre-neoplastic and neoplastic lesions, such as glands with daughterglands, uterine leiomyoma and vaginal rhabdomyosarcoma.Conclusion: In conclusion, early life exposure to GBH affected the reproductive developmental programming increasing pre-neoplastic andneoplastic lesions in the uterus and vagina of aged rats. The enhancedsensitivity to E2 and the increased E2/P4 serum levels could be possiblemechanisms of induction of carcinogenic and endocrine disrupting effectsof GBH.