KRÜPPEL-LIKE FACTOR 6 AND OXIDATIVE STRESS IN HUMAN EXTRAVILLOUS TROPHOBLAST CELLS

KOURDOVA, LUCILLE T; MIRANDA, ANDREA L; RACCA, A.C.; GENTI-RAIMONDI, S.; PANZETTA-DUTARI, G.M.

Buenos Aires

Congreso; SAIB 2017 - Reunión conjunta de Sociedades; 2017

Oxidative stress implies an imbalance between the generation of reactive oxygen species (ROS) and their clearance by defensive antioxidant molecules and mechanisms. Normal pregnancy requires an active placental antioxidant system to keep ROS level under control for normal trophoblast proliferation, invasion, and angiogenesis. On the other hand, impaired redox homeostasis is associatedwith miscarriage, preeclampsia, intrauterine growth restriction, and preterm birth. Krüppel-like factor 6 (KLF6) is a ubiquitous transcription factor enriched in the placenta. It has been implicated in angiogenesis, proliferation, apoptosis, and differentiation. However, its function is highly dependent on the cell context. We have previously demonstrated that KLF6 regulates the expression of pregnancy related genes such as PSG and β-hCG, it is required for propertrophoblast syncytialization, and hypoxia induces its expression in human term placenta and extravillous trophoblastic cells. Herein, we evaluated whether KLF6 contributes to ROS balance in HTR8/SVneo cells, a cell line derived from human first trimester extravillous trophoblasts. KLF6 expression was early up-regulated in response to chemical hypoxia, decreased serum concentration, and chlorpyrifos treatment, a pesticide that generates ROS. KLF6 expressionwas down-regulated with a specific siRNA (siK) or a non-targeting siRNA (siC). Cell viability was not compromised after 48 h of transfection; however, a significant increase in ROS was detected by flow cytometry in siK-cells compared to siC ones. In addition, higher levels of ROS were detected in siK-cells after 3 and 6 h of H2O2 treatment. Moreover, upon exposure to H2O2 for 24 h viability was reduced in KLF6-silenced cells compared to siC transfected and non-transfected cells. Altogether, these results suggest that KLF6 contributes to extravillous trophoblast survival under oxidative stress conditions. Supported by FONCyT, CONICET, SECyT-UNC