Effect of chemotherapy on the prepubertal testis

Abstract

With an increase in long term survival rates for childhood cancers, more focus is now being placed on quality of life issues resulting from long term side effects of treatment. Infertility in later life is a known side effect of chemotherapy in patients that have survived childhood cancer. The testis contains two irreplaceable cell populations for subsequent fertility, the proliferating stem germ cells and the somatic Sertoli cells that support the development of the germ cells. First different methods to culture mouse testicular tissue were examined and then compared to in vivo time points to validate the model used. In order to examine which cell type is effected by exposure to chemotherapy, neonatal mouse testes were exposed to varying concentrations of either phosphoramide mustard (PM), cisplatin (CIS), or doxorubicin (DOX) on the second day of a four day in vitro culture (n ≥ 8 for each treatment). Immunofluorescent analysis showed that exposure to PM, CIS and DOX resulted in a specific loss of germ cells in the neonatal mouse testis at doses within the range found in patients’ serum. Finally, preliminary cultures using human foetal tissue were developed in order to compare the effects of chemotherapy between the mouse and human. In conclusion, the results presented here suggest that infertility following chemotherapy in childhood is due to a specific loss of germ cells from the seminiferous tubules.