Amniotic fluid-derived exosomes attenuated fibrotic changes in POI rats through modulation of the TGF-β/Smads signaling pathway
Nazdikbin Yamchi N. Ahmadian S. Mobarak H. Amjadi F. Beheshti R. Tamadon A. Rahbarghazi R. Mahdipour M.
December 2023BioMed Central Ltd
Journal of Ovarian Research
2023#16Issue 1
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.
Amniotic derived exosome , Fertility restoration , Ovarian tissue regeneration , Premature ovarian insufficiency
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Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Faculty of Veterinary Medicine, Shabestar Islamic Azad University, Shabestar, Iran
PerciaVista R&D Co., Shiraz, Iran
Department for Scientific Work, Marat Ospanov Medical University, West, Aktobe, Kazakhstan
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Stem Cell Research Center
Faculty of Veterinary Medicine
PerciaVista R&D Co.
Department for Scientific Work
Drug Applied Research Center
Department of Applied Cell Sciences
Department of Reproductive Biology
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