Molecular and cellular response of human trophoblast cells exposed to chlorpyrifos

RIDANO ME; RACCA AC; GENTI-RAIMONDI S; PANZETTA DE DUTARI G.

Congreso; XLVIII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2012

SAIB

Chlorpyrifos (CPF) is one of the most widely used pesticides. Several reports suggest that prenatal exposure leads to cognitive impairments and increased risk of pregnancy disorders. Although placental function and differentiation is intimately related to fetal health, information on CPF´s effect on placenta is still scarce. Previously, we reported that CPF increased the expression of the ABCG2 efflux transporter and βhCG subunit in JEG-3 choriocarcinoma cell line. Herein, we assessed primary human cytotrophoblasts (CTBs) response to CPF exposure. CTBs purified from normal term placentas were exposed to 0-100 μM CPF during 22 or 64h. Under control conditions, CTBs do not proliferate but differentiate and fuse forming syncytium-like structures. In the presence of CPF, no morphological signs of cell damage or impairment of syncytialization were detected, while mitochondrial metabolic rate, measured using MTT, was augmented. qRT-PCR revealed an early (22h) increase in βhCG and p-glycoprotein efflux transporter and a late (64h) increase in ABCG2 expression in CPFtreated CTBs. Instead, mRNA level of the PSG3 differentiation marker and KLF6 transcription factor remained unmodified at the time points assayed. These results suggest that villous trophoblasts may activate protection mechanisms in order to preserve placental function. Supported by CONICET, FONCyT, MinCyT & SECyT-UNC.