Human UC-MSC-derived exosomes facilitate ovarian renovation in rats with chemotherapy-induced premature ovarian insufficiency

Front Endocrinol (Lausanne). 2023 Jul 26:14:1205901. doi: 10.3389/fendo.2023.1205901. eCollection 2023.

Abstract

Premature ovarian insufficiency (POI) induced by chemotherapy is an intractable disorder with a considerable incidence that commonly results in insufficient fertility and concomitant complications in female patients. Due to limitations in the current progress in POI diagnosis and treatment, there is an urgent need to develop novel remedies to improve ovarian function and protect fertility. The ameliorative effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and exosomes derived from them in POI treatment could be a new hope for patients. Herein, we identified exosomes from hUCMSCs (hUCMSC-Exos). Then, systematic infusion of hUCMSC-Exos was accomplished via tail intravenous injection to investigate the feasibility of the treatment of rats with chemotherapy-induced POI by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). Ovarian functions in the indicated group were evaluated, including oestrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, proliferation and apoptosis of granulosa cells (GCs), and reproductive ability testing. Furthermore, the potential influence of hUCMSC-Exos on ovarian tissues was illuminated by conducting RNA-seq and multifaceted bioinformatics analyses. POI rats with hUCMSC-Exos transplantation exhibited a decrease in follicle-stimulating hormone (FSH) and apoptosis of GCs but an increase in oestradiol (E2), anti-Müllerian hormone (AMH), and the number of ovarian follicles and foetuses in the uterus. And the immunomodulation- and cellular vitality-associated gene sets in rats had also undergone moderate changes. Our data indicated the feasibility of hUCMSC-Exos in improving ovarian function and protecting fertility in chemotherapy-induced POI rats. HUCMSC-Exos can improve the local microenvironment of ovarian tissue in POI rats by participating in immune regulation, cellular viability, inflammation regulation, fibrosis and metabolism, and other related signal pathways.

Keywords: HUCMSCs; exosomes; gene expression profile; ovarian function; premature ovarian insufficiency (POI).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / adverse effects
  • Exosomes* / metabolism
  • Female
  • Humans
  • Menopause, Premature*
  • Primary Ovarian Insufficiency* / chemically induced
  • Primary Ovarian Insufficiency* / pathology
  • Primary Ovarian Insufficiency* / therapy
  • Rats

Substances

  • Antineoplastic Agents

Grants and funding

This work was supported by the Science and Technology Project of Guizhou (Qiankehejichu-[2020]1Y337), Zhukehetong ([2019]9-1-1), Qiankehejichu-ZK[2023] Key project 040, 2019 Science and Technology Project of Health Commission of Guizhou Province (gzwjkj2019-1-008), the National Natural Science Foundation of China (82260261), the National Natural Science Foundation of China (82260031), the Science and Technology Projects of Guizhou Province (QKH-J-ZK [2021]-107), and the Natural Science Foundation of Jiangxi Province (20212BAB216073, 20224BAB206077).