Co-administration of Bone Marrow-derived Mesenchymal Stem Cells and Royal Jelly Improved Ovarian Tissue Function in PCOS Rats via the Regulation of Inflammation and Angiogenesis.

BACKGROUND: This study aimed to investigate the possible restorative effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) along with royal jelly (RJ) on a rat model of polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: In this experimental study, 50 female Wistar rats (150-200 g) were randomly assigned to five groups: control, PCOS, PCOS+BM-MSCs, PCOS+RJ, and PCOS+BM-MSCs+RJ. PCOS was induced by subcutaneous injection of testosterone enanthate (100 mg/kg). BM-MSCs were administered via tail vein every two weeks. RJ was given orally (500 mg/kg/day) for 14 days. Two weeks post-treatment, blood samples were analyzed for interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX2), using ELISA. Ovarian tissues were examined histologically, and bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) levels were measured by Western blot. RESULTS: RJ and BM-MSCs improved abnormal follicle structure in PCOS rats. The mean serum levels of IL-6 (P=0.016) and TNF-α (P<0.0001) were significantly reduced in the PCOS+RJ+BM-MSCs group compared to the PCOS rats. However, there was no statistically significant reduction in expression of VEGF (P=0.090) and COX-2 (P=0.104). The expression levels of BMP15 and GDF9 proteins were significantly reduced in PCOS rats compared to the control group (P<0.0001), while in the PCOS+RJ+BM-MSCs group, the expression of BMP15 (P<0.001) and GDF9 (P<0.0001) proteins increased compared to the PCOS group. CONCLUSION: RJ and BM-MSCs may restore ovarian function by regulating inflammation, angiogenesis, and oocyte quality.