(339) Bgp-15 Treatment Attenuates Collagen Deposition, Favors Angiogenesis, and Improves Follicle Survival in Mice Ovaries After Subcutaneous Transplantation

Paulo H.A. Campos¹; Luiza A.A.C. Pereira¹; Karine S.S.A Dias¹; Larissa A. Freitas¹; Camila S. Ferreira¹; Amanda P. Paz¹

¹ Laboratory for Research about Reproductive Biology, Federal University of São João del Rei, São João del Rei, Minas Gerais, Brazil

Abstract Text:

Ovary transplantation is a promising alternative for fertility preservation, however, for its broad application this technique still requires further studies to improve the quality of derived oocytes. BGP-15 is a hydroxylamine derivative that optimizes mitochondrial function, reduces collagen deposition and reverse aging effects in ovaries. Thus, the aim of this study was to investigate the effect of BGP-15 treatment on transplanted ovarian function and folliculogenesis progression. Female C57Bl6J mice (n=34, 4 weeks-old 6986150322) were submitted to ovary transplantation followed by a 5 days BGP-15 (i.p. - 10 mg/kg) treatment or vehicle (daily). 6 or 22 days after transplantation, euthanasia was performed and ovaries were directed to follicular quantification, immunohistochemistry, and Picrosirius Red assay (PSR). For the oocyte recovery,  20UI of hCG was administered and 48h later, ovaries were collected and punctured. Body weight and estrous cycle were also evaluated. BGP-15 treatment did not alter biometric parameters (p >0.05). An increased number of transitional (p=0.0134 - Vehicle 1.394±0.1226; BGP-15 2.298±0.2615) and primary (p=0.0148 - Vehicle 1.500±0.1409; BGP-15 2.185±0.2724) follicles were observed on the BGP-15 treated animals, contrasting to a lower number of secondary (p=0.0441 - Vehicle 1.700±0.3; BGP-15 1.000±0.01) and atretic (p< 0.0001 - Vehicle 0.2394±0.08140; BGP-15 0.04317±0.01730) on the sixth day. 22 days after transplantation, the number of primordial (p=0.0259, Vehicle 2.415± 0.2324; BGP-15 3.266±0.2429), transitional (p=0.0206, Vehicle 1.543±0.1553; BGP-15 2.730±0.4644), primary (p=0.0125, Vehicle 1.500±0.1409; BGP-15 2.125±0.2025), secondary (p=0.0428, Vehicle 1.400±0.1633; BGP-15 2.733±0.4925) and atretic (p=0.0381, Vehicle 3.386±0.3702; BGP-15 2.600±0.1884) follicles were increased by BGP-15 treatment. An increased follicular ratio was observed on the BGP-15 treated animals concerning the secondary/primary follicles (p=0.0006, Vehicle 0.01061±0.006719; BGP-15 0.1445±0.02343). An increased diameter of transitional oocytes was observed on the BGP-15 (p=0.377, Vehicle 10.35±0.6767; BGP-15 11.87±0.9350). A lower macrophage number (F480+) both in the capsule (p< 0.0001 - Vehicle 19.50±1.338; BGP-15 8.275±0.9157) and in the ovary  (p< 0.0001 - Vehicle 48.18±2.119; BGP-15 5.750±0.7105) were observed on the BGP-15 treated. A decreased PSR positive area in the capsule (p=0.0344, Vehicle 0.02071±0.004844; BGP-15 0.00873±0.001982) and in the ovary (p=0.0465, Vehicle 0.007568±0.002311; BGP-15 0.002409±0.0009132) were observed on the BGP-15 treated. An increased number of vessels (CD31+) were observed on BGP-15 treated (p< 0.0001 - Vehicle 39.2±3.294; BGP-15 43.24±2.689). Our findings demonstrated, for the first time in the literature, that BGP-15 treatment was able to reduce ovarian collagen deposition, which could act to improve transplant quality through the reduction of fibrosis and promote neovascularization.
Finantial support: CAPES, CNPQ, FAPEMIG, FINEP, GOV. MG, UFSJ.