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

RIDANO, MAGALÍ; FLORES-MARTÍN JÉSICA; MAGNARELLI GLADIS; GENTI-RAIMONDI SUSANA; PANZETTA-DUTARI GRACIELA

San Miguel de Tucumán, Tucumán

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

SAIB

Gene expression and cellular differentiation are tightly controlled by genetic and epigenetic mechanisms which may be disrupted by toxic compounds. Epidemiological data suggest an association between chronic organophosphate (OP) exposure of pregnant women and an increased risk of spontaneous abortion, low weight offspring and intrauterine growth restriction. To address the molecular mechanism(s) underling these effects, we hypothesized that OPs exposition alter placenta cell morphology and gene expression. Human trophoblast derived JEG3 cell line was used as an in vitro model to test this hypothesis. In an initial approach, cellular viability was assayed to select chlorpyrifos, phosmet and methylazinphos concentrations for further experiments. Cell number with fragmented and/or condensed nuclei increased with OP concentration (50 and 100mM) 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 in GCM1 and KLF6 transcription factors and an increase in StarD7 expression. In addition, immunofluorescent StarD7 protein staining was augmented in the presence of OPs, especially in cells with condensed nuclei. These data suggest that the OPs used in these experiments impact on placental cell morphology and function. Supported by SACyT, CONICET, FONCyT, MinCyT of Córdoba and SECyT-UNC .