Nuclear morphology and gene expression are altered in human trophoblast cells by organophosphates

RIDANO ME; FLORES-MARTÍN J; MAGNARELLI G; GENTI-RAIMONDI S; PANZETTA-DUTARI GM

Tucuman

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2009

Gene expression and cellular differentiation are tightly controlledby genetic and epigenetic mechanisms which may be disrupted bytoxic compounds. Epidemiological data suggest an associationbetween chronic organophosphate (OP) exposure of pregnantwomen and an increased risk of spontaneous abortion, low weightoffspring and intrauterine growth restriction. To address themolecular mechanism(s) underling these effects, we hypothesizedthat OPs exposition alter placenta cell morphology and geneexpression. Human trophoblast derived JEG3 cell line was used asan in vitro model to test this hypothesis. In an initial approach,cellular viability was assayed to select chlorpyrifos, phosmet andmethylazinphos concentrations for further experiments. Cellnumber with fragmented and/or condensed nuclei increased withOP concentration (50 and 100µM) and incubation time (24 and 48h)instead, no major effect was observed on spontaneous cell fusion.RT-PCR analysis revealed that chlorpyrifos induced a reduction inGCM1 and KLF6 transcription factors and an increase in StarD7expression. In addition, immunofluorescent StarD7 protein stainingwas augmented in the presence of OPs, especially in cells withcondensed nuclei. These data suggest that the OPs used in theseexperiments impact on placental cell morphology and function.