GLYPHOSATE HERBICIDE: CARCINOGENIC POTENTIAL AND REPRODUCTIVE TOXICITY

VARAYOUD, JORGELINA; LORENZ V; GUERRERO SCHIMPF ML; GASTIAZORO MP; ZANARDI MV; DURANDO M; MILESI MM

Congreso; Reunión conjunta SAIC - SAi - AAFE; 2021

Glyphosate-based herbicides (GBHs) are the most widely applied pesticides in the world and are mainly used in association with GBH-tolerant crop varieties. Indiscriminate and negligent use of GBHs has promoted the emergence of glyphosate resistant weeds, and consequently the rise in the use of these herbicides. In addition, alarmingly increased levels of glyphosate, the active ingredient of all GBHs, have been detected in environmental matrixes and in foodstuff, becoming a matter of social concern. GBHs are composed of glyphosate and other chemicals known as co-formulants which enhance the herbicide action. Currently, the safety of glyphosate and its formulations remain to be a controversial issue. In 2015, the World Health Organization classified glyphosate as a ?carcinogen type 2a? or a probable human carcinogen; however, nowadays its carcinogenic potential is under discussion. Our research work focused on investigating whether glyphosate or GBH could exhibit carcinogenic potential and/or impair female fertility and fetal/placental growth. We performed in vitro and in vivo studies to evaluate the effects and elucidate the mechanisms of action of the herbicide. For in vivo studies, we exposed female rats during high sensitivity periods of life (perinatal and/or early postnatal period), and the effects were tested at adulthood. We analyzed endocrine disrupting endpoints and epigenetic markers using different experimental conditions focusing our attention on the uterus. The results indicate that glyphosate and GBH produce female subfertility by impairing the implantation process, and induce fetal growth retardation in their offspring. Both compounds show endocrine disrupting effects mediated, at least in part, by epigenetic dysregulation of key genes involved in uterine functional differentiation. Regarding carcinogenic potential, we found: i) higher sensitivity to 17β-estradiol in uterine tissue, ii) induction of preneoplastic and neoplastic lesions in mammary gland, uterus and vagina, and iii) stimulation of epithelial mesenchymal transition-related changes via ER-dependent pathway in Ishikawa cells. In conclusion, we provide evidence on adverse reproductive outcomes and carcinogenic properties of the herbicide. As our results indicate similar effects after glyphosate and GBH treatment, the active principle might be responsible for the deleterious effects. Epidemiological studies are a priority to evaluate possible deleterious effects on human health.