Repair of female reproductive function by GDF-9-overexpressing extracellular vesicles via ACVR1B/SMAD2 regulation in ovarian granulosa.

ABSTRACT: Aging in females is characterized by dysfunctional ovaries (DOs). While human umbilical cord mesenchymal stem cell (HucMSC)-derived extracellular vesicles (EVs) have shown promise in ameliorating DO, the mechanisms underlying their effects remain poorly understood. In this study, we investigated the therapeutic potential of growth differentiation factor 9 (GDF-9)-overexpressing EVs (GOEs) on granulosa cells. We identified the activin A receptor type 1B (ACVR1B) as a critical target for the restoration of ovarian function. Genetic modification of HucMSCs to overexpress GDF-9 resulted in the production of GOEs, which, through ACVR1B activation, induced SMAD2 phosphorylation in the nucleus, thereby rescuing ovarian function. These findings provide previously unknown insights into the mechanis

SUBMITTER: Zhang S 

PROVIDER: S-EPMC12693986 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature