Role of adipose-derived stem cell exosomes in paclitaxel-induced acute ovarian injury: An experimental approach

Paclitaxel (PTL) is commonly used in cancer therapy at varying doses and durations, often in combination with other chemotherapeutic agents. However, achieving therapeutic efficacy typically requires high doses, which are associated with considerable toxicity. Adipose-derived stem cells have shown therapeutic potential, particularly through the release of extracellular vesicles known as exosomes. This study investigated the potential protective effects of exosomes derived from adipose-derived mesenchymal stem cells (AMSC-Exos) in a rat model of PTL-induced acute ovarian injury. Twenty-eight rats were assigned to groups: control, PTL (7.5 mg/kg), AMSC-Exos (1 ×10⁶ exosomes), and PTL+AMSC-Exos (7.5 mg/kg PTL + 1 × 10⁶ exosomes). Three days after the administration, ovarian tissues were harvested for histological and biochemical analysis. Hematoxylin and eosin (H&E) and Masson's Trichrome (MT) staining revealed significant histopathological deterioration in the cortex and medulla of ovarian tissue in the PTL group compared to the PTL+AMSC-Exos group. Exosome treatment following PTL administration resulted in upregulation of VEGF and downregulation of HIF-1α, NF_KB-p65, and IL-1β immunostaining intensities. Additionally, AMH immunostaining intensity was increased in primary, preantral, and secondary follicles. Levels of TNF-α, IL-1β, and IL-6 were significantly lower in the exosome treated group than in the PTL group, according to the results of the ELISA. These findings demonstrate that AMSC-Exos exhibited beneficial effects against PTL-induced acute ovarian damage by reducing histopathological alterations, inflammation, and HIF-1α expression, while enhancing VEGF expression and ovarian reserve. AMSC-Exos may represent a promising therapeutic approach for preventing chemotherapy-induced ovarian toxicity.