Dingkun Pill-Mediated TGF-β1/Smad2 Pathway Effects on Granulosa Cell Proliferation and Apoptosis.

Abstract

To investigate influences of Dingkun Pill on granulosa cell proliferation and apoptosis (P&A) in polycystic ovary syndrome (PCOS) mice and its association with the TGF-&#x3b2;1/Smad2 signaling pathway (SPW) activity. Forty-eight female SD mice were rolled into experimental group (EG, Dingkun Pill), control group (CG, metformin), model group (MG, distilled water), and normal group (NG, distilled water), with 12 mice per group. The Beloosesky method was employed to establish the PCOS mouse model. Serum hormone (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T)), expression of vascular endothelial growth factor (VEGF) in rat ovarian tissue and expression of HOXA10 in endometrial tissue, cell P&A, and expression level (EL) of TGF-&#x3b2;1 and Smad2 were compared among groups. Compared to the MG, the EG and CG exhibited significantly reduced levels of FSH, LH, and testosterone, while estradiol levels were significantly elevated. Furthermore, granulosa cell proliferation was notably enhanced, and the apoptosis rate was significantly decreased (P&#x2009;<&#x2009;0.05). In addition, the expression of VEGF in ovarian tissue, as well as the expression of TGF-&#x3b2;1 and Smad2, was significantly lower in EG and CG compared to MG, while the expression of the HOXA10 gene in the endometrium was significantly increased (P&#x2009;<&#x2009;0.05). Compared to CG, EG showed higher ovarian VEGF expression and lower HOXA10 gene expression (P&#x2009;<&#x2009;0.05).Dingkun Pill notably improves serum hormone in a PCOS mouse model, inhibits granulosa cell apoptosis, and enhances granulosa cell proliferation activity. This effect is likely mediated through the inhibition of the TGF-&#x3b2;1/Smad2 SPW, suggesting a protective role of Dingkun Pill in PCOS.