Nuclear morphology and gene expresion in human trophobast cells by organophosphates.

RIDANO ME, FLORES-MARTÍN J, MAGNARELLI G, GENTI-RAIMONDI S, PANCETA-DUTARI

Tucumán. Argentina

Congreso; XLV Reunión Anual de investigación en Bioquímica y Biología Molecular; 2009

Gene expression and cellular differentiation are tightly controlled bygenetic and epigenetic mechanisms which may be disrupted by toxiccompounds. Epidemiological data suggest an association betweenchronic organophosphate (OP) exposure of pregnant women and anincreased risk of spontaneous abortion, low weight offspring andintrauterine growth restriction. To address the molecular mechanism(s)underling these effects, we hypothesized that OPs exposition alterplacenta cell morphology and gene expression. Human trophoblastderived JEG3 cell line was used as an in vitro model to test thishypothesis. In an initial approach, cellular viability was assayed toselect chlorpyrifos, phosmet and methylazinphos concentrations forfurther experiments. Cell number with fragmented and/or condensednuclei increased with OP concentration (50 and 100μM) and incubationtime (24 and 48h) instead, no major effect was observed onspontaneous cell fusion. RT-PCR analysis revealed that chlorpyrifosinduced a reduction in GCM1 and KLF6 transcription factors and anincrease in StarD7 expression. In addition, immunofluorescent StarD7protein staining was augmented in the presence of OPs, especially incells with condensed nuclei. These data suggest that the OPs used inthese experiments impact on placental cell morphology and function