Human Umbilical Cord-Derived Mesenchymal Stem Cell Secretome Modulates Ovarian TNF-α, Oxidative Stress, and Serum Estradiol in Letrozole-Induced PCOS Rats
Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, chronic inflammation, and oxidative stress. Current treatments mainly relieve symptoms without addressing ovarian damage. Human umbilical cord–derived mesenchymal stem cell (hUC-MSC) secretome is a cell-free product with anti-inflammatory, antioxidant, and regenerative effects that avoids cell-related risks, but its role in PCOS remains unclear. This study was conducted to evaluate its effects on ovarian tumor necrosis factor (TNF)-α, oxidative stress, and serum estradiol in letrozole-induced PCOS rats.
METHODS: Thirty female Wistar rats were assigned to a normal group, untreated PCOS-induced group, and PCOS-induced groups treated with either 200, 300, or 400 µL hUC-MSC secretome. PCOS was induced with letrozole for 21 days, and confirmed by vaginal cytology on day-22. Ovarian TNF-α expression, serum estradiol, ovarian malondialdehyde (MDA), and ovarian superoxide dismutase (SOD) activity were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), the thiobarbituric acid reactive substances (TBARS) assay, and the water-soluble tetrazolium salt (WST) assay, respectively.
RESULTS: Letrozole successfully induced PCOS characteristics, which was marked by persistent diestrus and ovarian histological alterations in PCOS-induced groups. Compared with the untreated PCOS group, group receiving 200 µL hUC-MSC secretome showed lower ovarian TNF-α expression and MDA levels, as well as higher SOD activity and serum estradiol concentrations, approaching normal control values, although these differences were not statistically significant. Compared with the other hUC-MSC concentrations, the 200 µL dose showed the most consistent trend across inflammatory, oxidative stress, and hormonal parameters.
CONCLUSION: Administration of hUC-MSC secretome, especially 200 µL dose, showed a trend toward reduced ovarian inflammation and oxidative stress in PCOS rats. These findings suggest that hUC-MSC secretome may have potential as a complementary treatment for PCOS.
KEYWORDS: polycystic ovary syndrome, hUC-MSC secretome, TNF-α, oxidative stress, estradiol
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DOI: https://doi.org/10.18585/inabj.v18i5.4283
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