Hypoxia-induced DEC1 mediates trophoblast cell proliferation and migration via HIF1α signaling pathway

• Expression of HIF-1ɑ and DEC1 was significantly reduced in villi of URSA compared to normal pregnant women. • Hypoxia induces the expression of DEC1 in HTR-8/SVneo cells. • DEC1 promotes trophoblast cell proliferation and migration through HIF1α signaling pathway under hypoxia. In early pregnancy, hypoxia is a typical extrinsic factor that regulates EVT functions including proliferation, migration and invasion which are essential for a successful pregnancy. Human differentiated embryonic chondrocyte-expressed gene 1 (DEC1), a hypoxia-regulated gene, has been reported to be overexpressed in several types of cancers. Given that the placenta and the cancer share several similarities with respect to their capacity to proliferate and invade adjacent tissues, we focused on the role of DEC1 on trophoblast function in a physiologically hypoxic environment, which may be associated with unexplained recurrent spontaneous abortion (URSA).In our study, we measured the expression of HIF-1α and DEC1 in first-trimester villi through real-time-PCR (RT-PCR) and immunohistochemical analysis. in vitro , DEC1 expression was downregulated in trophoblast cells via DEC1-specific shRNA plasmid transfection. The expression of DEC1 and HIF-1α was detected via western blotting and RT-PCR analysis. The proliferation and migration of HTR-8/SVneo cells were assayed using CCK-8 and Transwell migration assays, respectively.Our results indicated that the expression of DEC1 was significantly reduced in villi of URSA compared to that in normal pregnant women. in vitro , hypoxia induced the expression of HIF-1ɑ and DEC1 and upregulated proliferation and migration of the HTR-8/SVneo cells. Knockdown of DEC1 inhibited proliferation and migration of HTR-8/SVneo cells exposure to hypoxia. Furthermore, inhibition of HIF1α expression resulted in a significant decrease in DEC1. These findings illustrate that hypoxia-induced DEC1 expression promotes trophoblast cell proliferation and migration through the HIF1α signaling pathway, which plays an important role during placentation.