Amniotic fluid-derived exosomes attenuated fibrotic changes in POI rats through modulation of the TGF-β/Smads signaling pathway
Nahideh Nazdikbin Yamchi, Shahin Ahmadian, Halimeh Mobarak, Farhad Amjadi, Rahim Beheshti, Amin Tamadon, Reza Rahbarghazi, Mahdi Mahdipour
Abstract
In the current study, we investigated the regenerative effects of amniotic fluid exosomes (AF-Exos) in a rat model for premature ovarian insufficiency (POI). POI is a condition characterized by a decrease in ovarian function that can lead to infertility. We induced POI by administering cyclophosphamide (CTX) for 15 consecutive days, and then transplanted AF-Exos directly into both ovarian tissues. Four weeks later, we measured the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2), and performed histopathological evaluations using H & E and Masson's trichrome staining. We also monitored the expression of genes related to the TGF-β signaling pathway using real-time PCR and examined the fertility rate of POI rats after AF-Exos therapy. Histological analysis showed an increase in atretic follicles and a decrease in healthy follicle count after POI induction. Four weeks post-AF-Exos intervention, the healthy follicle count increased (p < 0.01) while the atretic follicle count decreased (p < 0.001). In parallel, the deposition of collagen fibers also decreased following AF-Exos transplantation. The concentrations of FSH and LH hormones in sera remained unchanged after injection of AF-Exos, while E2 levels increased (p < 0.05). The expression of Smad-4 (p < 0.01) and Smad-6 (p < 0.05) was upregulated in POI rats that received AF-Exos, while Smad-2, TGF-β1, TNF-α, and IL-10 remained statistically unchanged. Our records showed a notable increase in litter number after AF-Exos compared to the non-treated POI rats. These results suggest that AF-Exos transplantation has the potential to restore ovarian function through the TGF-β/Smads signaling pathway in POI rats.