LncPVT1 modulates decidualization and links to recurrent spontaneous abortions via glucose and lipid metabolic regulation.

Recurrent spontaneous abortion (RSA), defined by the occurrence of two or more consecutive pregnancy losses, significantly affects women’s quality of life. However, the intricate and complex mechanisms still pose bottlenecks in the diagnosis and treatment of RSA. Transcriptome analysis of decidual tissue, along with pathway analysis of differentially expressed genes, revealed that the most significant differences were observed in pathways related to linoleic acid metabolism, glycolysis/gluconeogenesis, glycerophospholipid metabolism, and arachidonic acid metabolism, all of which are integral to glucose and lipid metabolism. Through upstream mechanistic studies, it has been found that long non-coding plasmacytoma variant translocation 1 (lncPVT1) plays a crucial regulatory role in modulating these pathways. The present study aimed to verify the hypothesis that lncPVT1 modulates the biological functions of decidual tissue in RSA and to investigate the upstream mechanism involved. It was found that lncPVT1 was overexpressed in individuals with RSA. Furthermore, knockdown of lncPVT1 enhanced the proliferation, migration, and invasion of human endometrial stromal cells while decreasing apoptosis. In vitro experiments demonstrated that lncPVT1 knockdown influences the expression of key enzymes in the glycolytic pathway, including glucose transporter 1 (Glut1), glucose transporter 4 (Glut4), hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), as well as the expression of TNF receptor-associated factor 6 (TRAF6) in the lipid metabolism and RSA. Overall, our study demonstrated that lncPVT1 knockdown disrupts glycolysis and lipid metabolism, subsequently impacting the incidence of RSA. This study provides novel insights into understanding the molecular pathogenesis of RSA.