Krüppel-like factor 6 and oxidativestress in human extravillous trophoblast cells.

LUCILE KOURDOVA; ANDREA MIRANDA; RACCA ANA; GENTI DE RAIMONDI SUSANA; PANZETA DE DUTARI GRACIELA

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Oxidative stress implies an imbalance between the generation ofreactive oxygen species (ROS) and their clearance by defensive antioxidantmolecules and mechanisms. Normal pregnancy requiresan active placental antioxidant system to keep ROS level undercontrol for normal trophoblast proliferation, invasion, and angiogenesis.On the other hand, impaired redox homeostasis is associatedwith miscarriage, preeclampsia, intrauterine growth restriction, andpreterm birth. Krüppel-like factor 6 (KLF6) is a ubiquitous transcriptionfactor enriched in the placenta. It has been implicated in angiogenesis,proliferation, apoptosis, and differentiation. However, itsfunction is highly dependent on the cell context. We have previouslydemonstrated that KLF6 regulates the expression of pregnancyrelated genes such as PSG and β-hCG, it is required for propertrophoblast syncytialization, and hypoxia induces its expression inhuman term placenta and extravillous trophoblastic cells. Herein, weevaluated whether KLF6 contributes to ROS balance in HTR8/SVneocells, a cell line derived from human first trimester extravilloustrophoblasts. KLF6 expression was early up-regulated in responseto chemical hypoxia, decreased serum concentration, and chlorpyrifostreatment, a pesticide that generates ROS. KLF6 expressionwas down-regulated with a specific siRNA (siK) or a non-targetingsiRNA (siC). Cell viability was not compromised after 48 h of transfection;however, a significant increase in ROS was detected byflow cytometry in siK-cells compared to siC ones. In addition, higherlevels of ROS were detected in siK-cells after 3 and 6 h of H2O2treatment. Moreover, upon exposure to H2O2 for 24 h viability wasreduced in KLF6-silenced cells compared to siC transfected andnon-transfected cells. Altogether, these results suggest that KLF6contributes to extravillous trophoblast survival under oxidative stressconditions