Pathological changes in Sertoli cells and dysregulation of divalent metal transporter 1 with iron responsive element in the testes of idiopathic azoospermia patients

Iron is essential for rapidly dividing spermatocytes during normal mammalian spermatogenesis. Decreased transferrin and transferrin receptor levels were observed in seminal plasma from idiopathic azoospermia (IA) patients, suggesting disturbed iron metabolism in IA testes. However, how Sertoli cells (SCs) contribute to the iron homoeostasis in IA is still unclear. In this study, we analysed 30 IA and 30 age-matched obstructive azoospermia (OA) patients undergoing testicular sperm aspiration (TESA). SCs hyperplasia was indicated by higher SC density and Ki-67 labelling index in the IA TESA specimens. The attenuated expression of superoxide dismutase (SOD) suggested an impaired antioxidative capacity in IA testes. We further detected increased levels of iron importer divalent metal transporter 1 with iron responsive element (DMT1 + IRE) in IA testes, whereas the increasing trend of iron exporter ferroportin 1 (FPN1) was not statistically significant. Next, we demonstrated that iron regulatory protein 1 (IRP1) and hypoxia-inducible factor-1α (HIF-1α), which can potentially bind to the IRE and hypoxia-responsive element in the DMT1 + IRE mRNA, were both up-regulated in IA testes. Unexpectedly, HIF-2α was down-regulated in IA testes. These results indicate that there is a dysregulation of DMT1 + IRE in IA testes, which might due to the up-regulation of IRP1 and HIF-1α.