Dysregulation of angiogenesis-specific signalling in adult testis results in xenograft degeneration

Ectopic xenografting of testis is a feasible option for preservation of male fertility and angiogenesis plays a pivotal role in xenograft survival and functionality. When compared to immature testis, the adult testis is unable to establish functional xenografts due to potentially lower efficiency to induce angiogenesis. The precise molecular mechanism, however, remains elusive. In the present study, we compared adult and immature testis xenografts for survival, maturation and germ cell differentiation. Further, we evaluated differential expression of angiogenesis signalling-specific proteins in adult and immature testis and their xenografts. Results showed that adult testis xenografts degenerated whereas immature testis xenografts survived and established spermatogenesis with the production of haploid germ cells. Protein expression analysis demonstrated that immature testis xenografts were able to establish angiogenesis either through eNOS activation via VEGF and PI3K/AKT or through EGFR-mediated STAT3 pathway. The role of ERK/MAPK pathway in xenograft angiogenesis was ruled out. The absence or reduced expression of angiogenesis-specific proteins in adult testis and its xenografts possibly resulted in poor angiogenesis and in their subsequent degeneration. This study provides insight into angiogenesis mechanism that can be utilized to augment testis xenografting efficiency.