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<p>Polycystic ovarian syndrome (PCOS) is a common endocrine-metabolic condition characterized by persistent anovulation, and hormonal imbalance leading to disrupted follicular maturation, and overall ovarian dysfunction. This study aimed to investigate the regenerative effects of adipose-derived mesenchymal stem cell-derived exosomes (AD-MSCs-Exo) on ovarian restoration, and granulosa cells (GCs) functionality in a PCOS murine model. PCOS was induced via a single subcutaneous injection of estradiol valerate. Exosomes were isolated from AD-MSCs using the ExoCIB kit and characterized by DLS, TEM and flowcytometery. NMRI mice received intraperitoneal injection of AD-MSCs-Exo (25, 50, 75, and 100&#xa0;µg/kg body weight) twice over a two-week period. Following treatment, the mice were anaesthesia and sacrificed by cervical dislocation. The harvested ovarian tissues were subjected to histological assessment; FSH, LH, and estradiol levels were measured from serum. Further, GCs were isolated, and identified through FSH expression. Subsequently, the levels of GCs key regulator genes including FOXO3, Map1lc3b, and SF-1 were assessed by qRT-PCR. AD-MSCs-Exosome-like nanovesicles isolated in range of 30–80&#xa0;nm with bi-membrane spherical shape and 54.8% expression of CD9. The hormonal analysis revealed improved estradiol levels and a lowered LH/FSH ratio, indicating endocrine stabilization under exposure with AD-MSCs-Exo. In addition, treatment with AD-MSCs-Exo significantly improved ovarian histoarchitecture, and the optimum response was observed following exposure to 75&#xa0;µg/kg of AD-MSCs-Exo. However, administration of the highest dose (100&#xa0;µg/kg) was associated with inflammatory responses and partial tissue degeneration. Gene expression analysis also showed a marked up-regulation of FOXO3, along with increased Map1lc3b and SF-1 levels. Accordingly, AD-MSCs-Exosome like nanovesicles at optimum concentration exert regenerative effects on PCOS-induced ovarian dysfunction, which emphasizes the necessity for precise dose selection to achieve maximal therapeutic efficacy as a promising cell-free strategy for PCOS treatment.</p>

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Therapeutic Effects of Adipose-Derived Mesenchymal Stem Cell Exosome like Nanovesicles on Granulosa Cell Function in a Mouse Model of Polycystic Ovarian Syndrome: Involvement of FOXO3, Map1lc3b, SF-1 Genes

  • 期刊论文

  • 发表日期：

    2026年7月1日

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  • Fatemeh Khorram,
  • Elaheh Amini,
  • Mahnaz Azarnia,
  • Azadeh Niknejad

摘要

Polycystic ovarian syndrome (PCOS) is a common endocrine-metabolic condition characterized by persistent anovulation, and hormonal imbalance leading to disrupted follicular maturation, and overall ovarian dysfunction. This study aimed to investigate the regenerative effects of adipose-derived mesenchymal stem cell-derived exosomes (AD-MSCs-Exo) on ovarian restoration, and granulosa cells (GCs) functionality in a PCOS murine model. PCOS was induced via a single subcutaneous injection of estradiol valerate. Exosomes were isolated from AD-MSCs using the ExoCIB kit and characterized by DLS, TEM and flowcytometery. NMRI mice received intraperitoneal injection of AD-MSCs-Exo (25, 50, 75, and 100 µg/kg body weight) twice over a two-week period. Following treatment, the mice were anaesthesia and sacrificed by cervical dislocation. The harvested ovarian tissues were subjected to histological assessment; FSH, LH, and estradiol levels were measured from serum. Further, GCs were isolated, and identified through FSH expression. Subsequently, the levels of GCs key regulator genes including FOXO3, Map1lc3b, and SF-1 were assessed by qRT-PCR. AD-MSCs-Exosome-like nanovesicles isolated in range of 30–80 nm with bi-membrane spherical shape and 54.8% expression of CD9. The hormonal analysis revealed improved estradiol levels and a lowered LH/FSH ratio, indicating endocrine stabilization under exposure with AD-MSCs-Exo. In addition, treatment with AD-MSCs-Exo significantly improved ovarian histoarchitecture, and the optimum response was observed following exposure to 75 µg/kg of AD-MSCs-Exo. However, administration of the highest dose (100 µg/kg) was associated with inflammatory responses and partial tissue degeneration. Gene expression analysis also showed a marked up-regulation of FOXO3, along with increased Map1lc3b and SF-1 levels. Accordingly, AD-MSCs-Exosome like nanovesicles at optimum concentration exert regenerative effects on PCOS-induced ovarian dysfunction, which emphasizes the necessity for precise dose selection to achieve maximal therapeutic efficacy as a promising cell-free strategy for PCOS treatment.