Glyphosate herbicide: carcinogenic potential and reproductive toxicity

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

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2021

Glyphosate-based herbicides (GBHs) are the most widelyapplied pesticides in the world and are mainly used inassociation with GBH-tolerant crop varieties. Indiscriminateand negligent use of GBHs has promoted the emergenceof glyphosate resistant weeds, and consequentlythe rise in the use of these herbicides. In addition, alarminglyincreased levels of glyphosate, the active ingredientof all GBHs, have been detected in environmental matrixesand in foodstuff, becoming a matter of social concern.GBHs are composed of glyphosate and other chemicalsknown as co-formulants which enhance the herbicideaction. Currently, the safety of glyphosate and its formulationsremain to be a controversial issue. In 2015,the World Health Organization classified glyphosate asa “carcinogen type 2a” or a probable human carcinogen;however, nowadays its carcinogenic potential is underdiscussion. Our research work focused on investigatingwhether glyphosate or GBH could exhibit carcinogenicpotential and/or impair female fertility and fetal/placentalgrowth. We performed in vitro and in vivo studies toevaluate the effects and elucidate the mechanisms ofaction of the herbicide. For in vivo studies, we exposedfemale rats during high sensitivity periods of life (perinataland/or early postnatal period), and the effects weretested at adulthood. We analyzed endocrine disruptingendpoints and epigenetic markers using different experSYMPOSIA67imental conditions focusing our attention on the uterus.The results indicate that glyphosate and GBH producefemale 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 keygenes involved in uterine functional differentiation. Regardingcarcinogenic potential, we found: i) higher sensitivityto 17b-estradiol in uterine tissue, ii) induction ofpreneoplastic and neoplastic lesions in mammary gland,uterus and vagina, and iii) stimulation of epithelial mesenchymaltransition-related changes via ER-dependentpathway in Ishikawa cells. In conclusion, we provide evidenceon adverse reproductive outcomes and carcinogenicproperties of the herbicide. As our results indicatesimilar effects after glyphosate and GBH treatment, theactive principle might be responsible for the deleteriouseffects. Epidemiological studies are a priority to evaluatepossible deleterious effects on human health.