Weikert Steffen, Schrader Mark, Christoph Frank, Schulze Wolfgang, Krause Hans, Müller Markus, Miller Kurt
Department of Urology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
Int J Androl. 2005 Aug;28(4):224-9. doi: 10.1111/j.1365-2605.2005.00549.x.
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.
生殖细胞凋亡失调可能导致男性不育以及恶性转化。凋亡抑制蛋白(IAP)家族成员Survivin在所有最常见的人类恶性肿瘤中均过度表达,但在正常组织中几乎检测不到。我们使用实时聚合酶链反应(PCR)来定量检测正常睾丸组织(n = 22)、生精功能缺陷睾丸组织(n = 26)和睾丸生殖细胞肿瘤(TGCTs;n = 16)中Survivin mRNA的表达。Survivin在正常睾丸组织中高水平表达。不育患者睾丸组织中Survivin水平与生精功能障碍的严重程度呈负相关(p < 0.001),在大多数减数分裂前生精停滞的标本以及所有生精细胞发育不全的标本中均未检测到Survivin的表达。与正常睾丸组织相比,TGCTs中Survivin的表达水平较低。虽然在大多数具有未分化成分的TGCTs中检测到了Survivin的表达(13例中有12例),但在所有成熟畸胎瘤(n = 3)中均未检测到。这些数据表明,Survivin在正常和转化的生殖细胞中均有表达。其在生精障碍中的下调表明,Survivin可能有助于维持生殖细胞增殖和凋亡之间的正常平衡。在TGCTs中,Survivin的表达似乎随着体细胞分化而消失。