Chlorpyrifos exposure induces trophoblast barrier and stroma alterations in Human Chorionic villous Explants

RIDANO, M.E; RACCA A; FLORES MARTIN J; BEVILACQUA E; GENTI RAIMONDI S; FRETES RE; PANZETTA DUTARI G

Mar del Plata, Buenos Aires

Congreso; VI SLIMP | V LASRI: Interacción Materno-Fetal: Desde la Fertilización hasta la Próxima Generación; 2015

Sociedad Latinoamericana de Interacción Materno-Fetal y Placenta

Chlorpyrifos (CPF) is one of the most widely used organophosphate pesticides(OP). Although an increased risk of pregnancy disorders has beenreported in pregnant women exposed to these pesticides, the effects of OPon human placenta remain poorly investigated.We have previously shownthat cell lines and primary cultures of villous trophoblast cells are quiteresistant to CPF cytotoxicity, even at concentrations in the higher range ofpotential human exposure. However, morphological alterations wereobserved in placental villous explants exposed to the same CPFconcentrations.Objectives: Here, our aim was to further characterize the effects of CPF onthe chorionic villous structure by histopathological analysis.Methods: Human placental explants from normal term placentas wereexposed to 5, 10, 50 and 100 mM CPF or 0.04% DMSO (diluent) or culturemedium alone for 36 h. Tissue was fixed, and prepared for histochemical(hematoxylin/eosin and Periodic acideSchiff staining), immunohistochemical(CK-7, bhCG, Ki67) or ultra-structural studies.Results: A dose-dependent damage on placental villi was observed in CPFtreatedexplants compared to control samples. Low CPF concentrationsinduced modifications in the morphology and arrangement of syncytiotrophoblastnuclei, thickening of the basal membrane, and alteration of thevillous stroma. Higher doses induced villous structural changes, tissuedegeneration and placental barrier disruption. In addition, cell proliferationdetected by Ki67 staining was reduced.Conclusions: The current results indicate that CPF alters the histologicalfeatures of chorionic villi after in vitro exposure to this pesticide. In addition,together with previous results, they suggest that CPF-induced damageon trophoblast cells depends on the interaction of the trophoblastlayer with the basal membrane or villous stroma.Supported by CONICET, FONCyT and SECyT-UNC