Quantification of survivin mRNA in testes of infertile patients and in testicular germ cell tumours: high levels of expression associated with normal spermatogenesis.
Deregulated apoptosis of germ cells may contribute to male infertility as well as malignant transformation. Survivin, an inhibitor of apoptosis (IAP), is overexpressed in all the most common human malignancies, but barely detectable in normal tissues. We used real-time polymerase chain reaction (PCR) to quantify survivin mRNA expression in normal testes (n = 22), testes with defective spermatogenesis (n = 26) and testicular germ cell tumours (TGCTs; n = 16). Survivin was expressed at high levels in normal testes. Testicular survivin levels in infertile patients were related inversely to the severity of spermatogenic failure (p <0.001), with a lack of expression in most specimens with pre-meiotic spermatogenic arrest and in all those with germ cell aplasia. Lower levels of expression were observed in TGCTs than in normal testes. While survivin expression was detected in most TGCTs with undifferentiated components (12 of 13), it was absent in all mature teratomas (n = 3). These data show that survivin is expressed in normal and transformed germ cells. Its downregulation in spermatogenic disorders indicates that survivin may contribute to the normal balance between germ cell proliferation and apoptosis. In TGCTs, survivin expression appears to be lost with somatic differentiation.
Deregulated apoptosis of germ cells may contribute to male infertility as well as malignant transformation. Survivin, an inhibitor of apoptosis (IAP), is overexpressed in all the most common human malignancies, but barely detectable in normal tissues. We used real-time polymerase chain reaction (PCR) to quantify survivin mRNA expression in normal testes (n = 22), testes with defective spermatogenesis (n = 26) and testicular germ cell tumours (TGCTs; n = 16). Survivin was expressed at high levels in normal testes. Testicular survivin levels in infertile patients were related inversely to the severity of spermatogenic failure (p <0.001), with a lack of expression in most specimens with pre-meiotic spermatogenic arrest and in all those with germ cell aplasia. Lower levels of expression were observed in TGCTs than in normal testes. While survivin expression was detected in most TGCTs with undifferentiated components (12 of 13), it was absent in all mature teratomas (n = 3). These data show that survivin is expressed in normal and transformed germ cells. Its downregulation in spermatogenic disorders indicates that survivin may contribute to the normal balance between germ cell proliferation and apoptosis. In TGCTs, survivin expression appears to be lost with somatic differentiation.