Effects of hypoxia inducible factors-1α on autophagy and invasion of trophoblasts

Clin Exp Reprod Med. 2012 Jun;39(2):73-80. doi: 10.5653/cerm.2012.39.2.73. Epub 2012 Jun 30.

Abstract

Objective: This study was undertaken to determine the effect of hypoxia inducible factor (HIF)-1α on the cell death, autophagy, and invasion of trophoblasts.

Methods: To understand the effect of HIF-1α, we inhibited HIF-1α using siRNA under normoxia and hypoxia conditions. Invasion assay and zymography were performed to determine changes in the invasion ability of HIF-1α. Western blotting and immunofluorescence were performed to determine some of the signal events involved in apoptosis and autophagy.

Results: There was no difference in cell death through the inhibition of HIF-1α expression by siRNA; however, the expression of LC3 and autophagosome formation increased. On the other hand, autophagy was increased, and the invasive ability of trophoblast cells decreased according to the inhibition of HIF-1α expression by siRNA. These experimental results mean that HIF-1α genes regulate the invasive ability of trophoblasts by increasing autophagy.

Conclusion: This study contributes important data for understanding the mechanism of early pregnancy implantation and the invasive ability of trophoblasts by defining the relationship between the roles of HIF-1α and autophagy.

Keywords: Hypoxia; Invasiveness; Placenta; Programmed cell death type II; Trophoblasts.