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

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

  • Sci Adv. 2025 Dec 12;11(50):eadw9006. doi: 10.1126/sciadv.adw9006.
Sichen Zhang 1,  Huidong Liu 1,  Tianyue Zhang 1,  Yansong Wang 2,  Mengtong Zhang 1,  Xiao Zhang 1,  Hansong Li 1,  Shuai Huang 1,  Lin Liang 1,  Ke Cheng 3,  Shaowei Wang 1
Affiliations

Affiliations

  • 1 Department of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology, No. 1 Dahua Road, Dong Dan, Beijing 100730, PR, China.
  • 2 Department of Research and Development, China Resources Zizhu Pharmaceutical Co. Ltd., No. 27, Chaoyang North Road, Chaoyang District, Beijing 100024, China.
  • 3 Department of Biomedical Engineering, Columbia University, NY, New York 10032, USA.
PMID: 41370396 DOI: 10.1126/sciadv.adw9006
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 mechanisms by which EVs mediate ovarian recovery and propose GOEs as a potential therapeutic strategy for the treatment of DO.

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