Single-cell RNA sequencing reveals the follicle microenvironment of patients with premature ovarian insufficiency

Abstract

Abstract Background Premature ovarian insufficiency (POI) has a highly heterogeneous etiology, but its pathogenesis remains unclear. Methods To investigate the follicle microenvironment of POI patients and identify potential targeted therapeutic strategies, we performed scRNA-seq on follicular fluid samples from normal individuals, older persons, and POI patients. Results A total of 87,323 cells were isolated and grouped into six clusters, T cells, B cells, neutrophils, basophils, mononuclear phagocytes, and granular cells. Further analysis demonstrated that the proportions of granulosa cells 6, which are characterized by high expression levels of MALAT1, NEAT1, XIST, KCNQ1OT1, and AC016831.5, and monocytes (characterized by high VCAN expression) were elevated in older individuals and POI patients, whereas the population of GDT cells (which express TRGC1 and TRDC) was decreased. We also found that the genes that were differently expressed in GDT cells and monocytes were enriched for ribosome and endoplasmic reticulum-related pathways. Moreover, the monocytes from older individuals and POI patients did not exhibit VEGFA/FLT1 interaction. These data suggest that the loss of VEGFA/FLT1 interaction in monocytes, along with enhanced ER and ribosome pathways may drive excess inflammation, which accelerates GC senility and the state of infertility. Conclusions This study provides new insights into the pathogenesis of POI and aging and highlights VEGFA/FLT1 interaction as a potential therapeutic strategy for reducing inflammation and treating POI.