严重寡精症ICSI精子供体的DAZ基因拷贝缺失研究

DAZ基因拷贝缺失与人类的生精障碍有关。为了解中国正常生精男性和ICSI中严重寡精症精子供体DAZ基因拷贝缺失的分布, 探讨DAZ基因拷贝数检测在严重生精障碍精子供体遗传缺陷筛查中的意义, 本研究运用多重PCR和PCR-RFLP技术, 对128例严重寡精症ICSI精子供体和287个正常生精男性的DAZ基因缺失进行了研究。发现DAZ1/DAZ2、DAZ3/DAZ4和全部4个拷贝缺失等3种拷贝缺失类型, 其中全部4个拷贝缺失仅见于严重寡精症患者, 频率为11.7%; DAZ1/DAZ2缺失的频率在严重寡精症患者中显著高于正常男性(9.4% vs 2.8%, P = 0.004); 在严重寡精症患者中DAZ基因拷贝完全缺失与DAZ1/DAZ2缺失的总发生率为21.1%。DAZ3/DAZ4缺失的频率在两组人群中无显著差异(7.0% vs 3.8%, P > 0.05)。这些结果提示, DAZ基因全部拷贝缺失是严重寡精症患者生精障碍的常见遗传病因, 而DAZ1/DAZ2缺失则可能是一种高风险因素。鉴于上述DAZ基因缺失在严重生精障碍精子供体中较高的发生率, 在应用ICSI进行辅助生育前, 建议对严重寡精症的精子供体进行DAZ基因全缺失与DAZ1/DAZ2共缺失筛查, 以评估其男性后代患病的风险。

Study on DAZ Gene Copy Deletion in Severe Oligozoospermia Sperm Donor for ICSI

Deletion of DAZ gene copies is related to spermatogenesis impairment. To investigate the distribution of DAZ gene copy deletions among Chinese men, we analyzed DAZ gene deletions by multiplex polymerase chain reaction (multi-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 128 infertile patients with severe oligozoospermia selected as semen donors for intracytoplasmic sperm injection (ICSI) and 287 normospermic men. Three patterns of DAZ gene deletions, namely DAZ1/DAZ2 deletion, DAZ3/DAZ4 deletion and complete deletion of all 4 DAZ copies, were found in the present study. Complete deletion of the entire DAZ family of genes was only present in 11.7% of severe oligozoospermic patients. The frequency of DAZ1/DAZ2 deletion was significantly higher in severe oligozoospermic patients than that in the controls(9.4% vs 2.8%, P = 0.004. The total frequency of complete DAZ deletion and DAZ1/DAZ2 deletion was 21.1%. No significant difference in the frequency of DAZ3/DAZ4 deletion was observed between the patient and control group (7.0% vs 3.8%, P > 0.05). These results suggest that complete DAZ deletion is a frequent genetic cause of severe oligozoospermia, and DAZ1/DAZ2 deletion is a high risk factor for the disease. Thus, it isnecessary to screen the two deletion patterns of DAZ genes in severely oligozoospermic sperm donors before ICSI during assisted reproduction.