P–376 S100P in syncytiotrophoblast regulates lipid metabolism during early pregnancy

Abstract

Abstract Study question Does S100P involve in the regulation of lipid metabolism in trophoblast syncytialization during the early stage of pregnancy? Summary answer S100P suppressed lipid droplets overloading in trophoblast syncytialization during the early stage of pregnancy. What is known already S100P is a 95-amino acid protein belongs to the large family of S100 calcium-binding proteins and is exclusively expressed in syncytiotrophoblast layer of placenta, enhancing trophoblast cells proliferation, motility and invasion. Recent studies indicated S100P was aberrantly expressed in various malignant tumors, promoting their proliferation, survival, the formation and invasion of vessels, and has a close relationship with their grade malignancy, hormone dependency and the drug-resistance. Syncytialization is trophoblast cells differentiated from cytotrophoblasts fused into multinucleated cell clusters with cell boundaries deficiency. Study design, size, duration Tissues were collected from elective first trimester pregnancy terminations of healthy people and patients with recurrent spontaneous abortion. Human trophoblast stem cells (hTSCs) were isolated from Week 6 to Week 8 of fresh placental tissues (n = 8) and use forskolin to induce syncytialization. Participants/materials, setting, methods Tissues were collected from elective first trimester surgical pregnancy terminations to determine localization, abundance and function of S100P. The level of S100P protein and gene was measured by Real-time quantitative PCR (RT-qPCR), western blot, ELISA and immunofluorescence in hTSC induced ST(2D)-TSCT. The lipid droplets were assessed by Oil red O stain, BODIPY and electron microscope. Serum S100P concentration in normal and recurrent miscarriage patients were measured by ELISA. Main results and the role of chance S100P was exclusively localized in syncytiotrophoblast layer of the placental villous from gestational weeks 6–8 (n = 4); S100p serum concentration was increased markedly as the gestation progressed (n = 40, p < 0.05); the protein abundance of S100P was increased during syncytialization of hTSCs; Lipid droplets increased during syncytialization and knockdown of S100P leads to trophoblast cell death with the overload of lipid droplet; The expression of S100P was down regulated and the amount of lipid droplets apparently accumulated in villus of recurrent miscarriage patients (n = 4). Limitations, reasons for caution The role of S100P on placenta lacks the evidence from animal models. Wider implications of the findings: S100P is an important factor facilitating in trophoblast syncytialization in the first trimester of pregnancy and could be a biomarker of the early pregnancy sustenance. Trial registration number Not applicable