DEVELOPMENTAL EXPOSURE TO A GLYPHOSATE-BASED HERBICIDE INCREASES THE RISK OF NEOPLASTIC LESIONS IN UTERUS AND VAGINA OF AGED RATS

GUERRERO SCHIMPF M; MILESI MM; GASTIAZORO MP; LUQUE EH; VARAYOUD J

Puerto Alegre

Congreso; II Latin American Congress of Clinical and Laboratorial Toxicology; 2018

Introduction: Glyphosate-basedherbicides (GBHs) have been one of the most intensive herbicide used over thelast two decades. In the last years, it has been controversy regarding itscarcinogenic potential. While the European Food Safety Authority concluded ?noevidence of carcinogenicity was confirmed in either rats or mice?, theInternational Agency for Research on Cancer found there is ?sufficient evidenceof carcinogenicity in animals?. Thus, the carcinogenic potential of glyphosateand GBHs in laboratory animals remains uncertain. Estrogens have beenimplicated as important etiologic agents of cancer in the female reproductivesystem. Increased serum 17â-estradiol (E2)/progesterone (P4) ratio has beendemonstrated to be a mechanism of carcinogenesis in estrogen-dependent tissues.Objectives: Investigatewhether a brief postnatal exposure to GBH disrupts estrous cyclicity andhormone steroid levels, and causes gynecologic neoplastic lesions in aged rats.Methodology: All proceduresused in this study were approved by the Institutional Ethics Committee of theSchool of Biochemistry and Biological Sciences (UNL). Female Wistar pups wereinjected subcutaneously with saline solution (control, C) or GBH at a dose of 2mg/kg/day (reference dose, EPA) on postnatal days (PND) 1, 3, 5, and 7. Animalswere kept with feed and water ad libitumwithout further treatment until adulthood. From PND120 the estrous cycle was dailymonitored by vaginal smears. In addition, blood from the tail was obtained at theestrous stage to determine E2 and P4 serum levels by RIA and ELISA,respectively. Finally, the animals were sacrificed at 20 months of age, and theuteri and vagina were dissected and processed for histopathology.Results/Discussion: GBH-exposedrats showed alterations in estrous cyclicity associated with changes in E2 andP4 serum levels. An increased level of E2 (C: 28.94±1.36 vs. GBH: 33.46±1.03 pg/ml, p<0.05) and decreased level of P4 (C:10.91±0.19 vs. GBH: 7.39±0.65 ng/ml,p<0.001) was detected in GBH-exposed rats. Control aged rats showed uterineglandular abnormalities (pre-neoplastic lesions) associated with aging, such asglands with squamous metaplasia and glands with daughter glands (GDG).GBH-exposed rats showed an increased incidence of GDG (C: 2/11 vs. GBH: 5/10). Furthermore, GBHexposure elicited the development of neoplastic lesions. Uterine leiomyoma (10%of rats) and vaginal rhabdomyosarcoma (20% of rats) were detected inGBH-exposed rats.Conclusions: Developmentalexposure to GBH increases the risk to develop pre-neoplastic and neoplasticlesions in the uterus and vagina of aged rats. A possible mechanisticexplanation of these effects could be associated with increased E2/P4 serum levelsand abnormal estrous cyclicity.Acknowledgments: This work wassupported by grants from CONICET, ANPCyT and UNL.