Pesticides and fertility: the effects of a brief postnatal exposure on uterine development and female fertility.

MA. MERCEDES MILESI, ; JORGE G. RAMOS,; MÓNICA M. MUÑOZ-DE-TORO,; PAOLA I. INGARAMO,; MA. PAULA GASTIAZORO, ; JORGELINA G. VARAYOUD, ; ENRIQUE H. LUQUE. ; MARLISE L. GUERRERO SCHIMPF,; VIRGINIA LORENZ,

Mar del Plata, Argentina

Otro; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clinica.; 2016

The developmental programming hypothesis suggeststhat abnormal stimuli that occur during critical periods ofdevelopment can permanently reprogram normal physiologicalresponses and, consequently, give rise to reproductivehealth effects later in life. Early life exposures tochemicals in general, and pesticides in particular, havebeen associated with reproductive pathologies such asinfertility and gynecologic tumors. Our research focuseson the effects of pesticides exposure on uterine developmentand their lasting consequences manifested later inlife. The pesticides that we evaluated are the insecticideendosulfan and the herbicide glyphosate. In Argentina,glyphosate-based herbicides are the most commonlyused, and although endosulfan has been banned in 2013,large quantities of this chemical continue to contaminatethe environment because of its high persistence and lipophilicity.Using a rat model of early postnatal exposurewe observed that low doses of endosulfan and low dosesof a glyphosate-based herbicide disrupt the expressionof genes that regulate uterine development and differentiationduring the pre-pubertal period. In addition, westudied long-term effects on: 1) reproductive performance,2) implantation and post-implantation processes, and 3)epigenetic modifications of endocrinedependent genes.The results showed that both pesticides affected femalefertility but in different ways. Low doses of endosulfandecreased the number of implantation sites. In the case ofthe glyphosate-based herbicide, there was an increasednumber of resorption sites. To address the effects ofpostnatal pesticide exposure on the pregnant uterusat the molecular level, we evaluated the endometrialproliferation and the expression of implantation and decidualization-associatedgenes. Both pesticides impairedendometrial proliferation and altered the expression ofendocrine-regulated gene pathways. In addition, we foundmodifications on &0A methylation status of uterine genes, 42 MEDICINA - Volumen 76 - (Supl. I), 2016showing evidence of epigenetic regulation of alteredgene expression due to a postnatal pesticide exposure.Based on the evidence presented here and previouslypublished data, we conclude that some pesticides arelikely to diminish fertility in a laboratory animal model.More studies are needed to identify whether these orother pesticides may contribute to the decline in humanfertility observed in the past decades.