BGP-15 Treatment Improves Follicle Growth and Alters Collagen Deposition in Mouse Transplanted Ovaries

Ovarian transplantation causes a loss of follicular reserve, requiring new strategies to optimize post-transplant follicular growth. This study investigated N-(2-hydroxy-3-piperidin-1-ylpropoxy)pyridine-3-carboximidamide; dihydrochloride (BGP-15), a mitochondrial modulator, as a follicular growth stimulator and a collagen-depositing inhibitor, thereby improving graft quality. In vitro, neonatal mouse ovaries were treated with different concentrations of BGP-15. In vivo, adult mice undergoing ovarian autotransplantation received 10 mg/kg of BGP-15. Follicular quantification, gene expression by qRT-PCR (Sirt1, Sirt3, Nampt, Foxo3a, KitL, Pten, Amh), collagen deposition by Picrosirius assay, neoangiogenesis, macrophage infiltration, biometric parameters, and the estrous cycle were evaluated. In vitro, 0.001 µM BGP-15 induced follicular growth. reducing the percentage of primordial follicles (p < 0.0001) and upregulating Sirt1 (p < 0.0001), Sirt3 (p = 0.026), Nampt (p = 0.002), Pten (p = 0.012), and downregulating Amh (p = 0.031). In vivo, BGP-15 treatment in transplanted mice resulted in an earlier resumption of the estrous cycle (p = 0.0458). After transplantation, BGP-15 improved follicular outcome on day 22, increasing healthy follicles (transitional p = 0.0206; primary p = 0.0125; secondary p = 0.0428) and reducing atretic follicles (p = 0.0381). Treated animals exhibited decreased macrophage numbers (p < 0.0001) and collagen deposition (ovary: p = 0.0465; capsule: p = 0.0344), and increased blood vessel density (p < 0.0001). BGP-15 improves follicular growth and survival in ovarian grafts, coinciding with mitochondrial gene dysregulation and reduced collagen deposition. These findings suggest BGP-15 as a promising candidate for improving follicular outcomes after ovarian transplantation.