Impact of Neutral Sphingomyelinase Inhibition on Small Extracellular Vesicle Production by Mural Granulosa Cells and In Vitro Folliculogenesis in Mice.

ABSTRACT: Small extracellular vesicles (sEVs) function as critical regulators of ovarian follicular development. Although several pathways, including one involving neutral sphingomyelinase (nSMase), contribute to sEV production, the specific pathway active in ovarian follicles has not been clearly identified. In this study, we investigated GW4869, a specific inhibitor of nSMase activity, to determine its impact on sEV production by mouse mural granulosa cells (MGCs), the primary source of follicular sEVs. We also examined how nSMase inhibition affects the in vitro growth of oocyte‒granulosa cell complexes (OGCs) derived from secondary follicles. Transcripts encoding nSMases (Smpd2 and Smpd4) were detected in MGCs, and GW4869 treatment significantly reduced sEV production in MGC monolayer cultures. C

SUBMITTER: Matsushita K 

PROVIDER: S-EPMC12529890 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature