Chlorpyrifos exposure induces trophoblast barrier and stroma alterations in human chorionic villous explants

RIDANO ME; RACCA A; FLORES-MARTIN, J; BEVILACQUA, E; GENTI DE RAIMONDI S; FRETES R.; PANZETTA DE DUTARI GM

Simposio; VI Latin American Symposium on Maternal-Fetal Interaction and Placenta (VI SLIMP)- V Latin American Symposium on Reproductive Immunology (V LASRI); 2015

SLIMP

Chlorpyrifos (CPF) is one of the most widely used organophosphate pesticides (OP). Although an increased risk of pregnancy disorders has been reported in pregnant women exposed to OP, the effects of these pesticides on human placenta remain poorly investigated. We have previously shown that throphoblast cell lines and primary cultures of villous trophoblast are quite resistant to CPF cytotoxicity, even at concentrations in the higher range of potential human exposure. However, morphological alterations were observed in placental villous explants exposed to the same CPF concentrations.Objectives: Here, our aim was to further characterize the effects of CPF on chorionic villous structure by histopathological analysis.Methods: Human placental explants from normal term placentas were exposed during 36 h to 5, 10, 50, or 100 µM CPF dissolved in DMSO. Controls with DMSO or culture media alone were included. Tissue was fixed, and prepared for hematoxylin/eosine and Periodic acid?Schiff staining, as well as, immunohistochemical (CK-7, βhCG, Ki67) and ultrastructure studies under a transmission electron microscopy.Results: A dose-dependent damage on placental villi was observed in CPF-treated explants compared to control samples. Low CPF concentrations induced modifications in the morphology and arrangement of syncytiotrophoblast nuclei, thickening of the basal membrane, and alterations of the villous stroma. Higher doses induced villi structural changes, tissue degeneration, and placental barrier disruption. In addition, cell proliferation detected by Ki67 staining was reduced.Conclusions: Present results indicate that in-vitro exposure to CPF alters histological features of the chorionic villi. In addition, together with previous results, they suggest that damage on trophoblast cells depends on the interaction of the epithelial layer with the basal membrane or villous stroma. Supported by CONICET, FONCyT, SECyT-UNC and MINCyT-Cba.