Oleic acid stimulation of motility of human extravillous trophoblast cells is mediated by stearoyl-CoA desaturase-1 activity

STUDY QUESTION: Do fatty acids regulate development and motility of human extravillous trophoblast cells (EVTs)? SUMMARY ANSWER: Oleic acid is a promising lipid molecule that has beneficial effects on motility and development of human EVTs. WHAT IS KNOWN ALREADY: Fatty acid uptake into trophoblast cells is important for maintaining cellular events during pregnancy, but the molecular mechanisms of action of various fatty acids, including trans fatty acids, saturated fatty acids and monounsaturated fatty acids, in EVT cell lines are not clear. STUDY DESIGN, SIZE, DURATION: Effects of oleic acid, elaidic acid, palmitic acid and stearic acid on HTR8/SVneo cells were assessed in diverse assays in a dose- and time-dependent manner. PARTICIPANTS/MATERIALS, SETTING, METHODS: Effects of fatty acids on cell proliferation, migration, invasion and apoptosis (Annexin V expression, propidium iodide staining, TUNEL and invasion assays) of HTR8/SVneo cells were determined. Signal transduction pathways in HTR8/SVneo cells in response to fatty acids were determined by Western blot analyses. Regulation of fatty acids on oxidative conditions in EVTs were determined and validated by measurement of production of cellular reactive oxygen species, intracellular concentrations of free Ca2+ and lipid peroxidation assays. MAIN RESULTS AND THE ROLE OF CHANCE: In present study, we confirmed different effects of oleic acid and elaidic acid on migration, invasion, proliferation and apoptosis of the EVT cell line, HTR8/SVneo. We also investigated stearoyl-CoA desaturase-1 (SCD1) to determine if its activity contributed to oleic acid-induced migration of HTR8/SVneo cells. Next, we analyzed cell signaling molecules mediated by oleic acid and elaidic acid treatment, including MAPK and PI3K/AKT pathways in HTR8/SVneo cells. We further established whether selective inhibition of signaling molecules altered the ability of fatty acids to cause changes in migration and proliferation of HTR8/SVneo cells. Last, we examined the regulatory effects of oleic acid and SCD1 on oxidative stress in HTR8/SVneo cells. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The lack of in vivo animal studies is a major limitation of this research. Effectiveness of oleic acid to stimulate migration of human EVT cells requires further investigation. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that oleic acid can play an important role in promoting invasion of human EVT cell lines while both trans fatty acids and saturated fatty acids are not conducive to normal placentation. This may have implications for the prevention of pre-eclampsia and intrauterine growth restriction. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by a grant from the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (No. HI15C0810) awarded to G.S. and (No. HI17C0929) awarded to W.L. There are no conflicts of interest.