Department of Obstetrics and Gynecology, Asahikawa Medical University, Asahikawa, Hokkaido 078-8510, Japan.
Asian J Androl. 2012 Jul;14(4):580-3. doi: 10.1038/aja.2011.180. Epub 2012 Mar 12.
Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormad1 is essential for mammalian gametogenesis as knockout male mice are infertile. Hormad1-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonemal complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 (c. 163A>G), SNP2 (c. 501T>G) and SNP3 (c. 918C>T), were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest (P<0.05). We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis.
遗传机制被认为是某些男性不育症的原因，但了解甚少。减数分裂是生殖细胞所特有的，对生殖至关重要。联会复合体是染色体配对、分离和重组的关键组成部分。Hormad1 对于哺乳动物的配子发生是必不可少的，因为敲除雄性小鼠是不育的。Hormad1 缺陷的睾丸在早期粗线期出现减数分裂停滞，无法观察到联会复合体。为了分析人类 HORMAD1 基因缺陷与因减数分裂停滞导致的人类无精子症之间的关联假说，对 30 名被诊断为因减数分裂停滞导致无精子症的日本男性的所有编码区域进行了突变分析，通过直接序列分析进行。通过序列分析，在exon 3、8 和 10 中发现了三个多态性位点，单核苷酸多态性 1（c.163A>G）、SNP2（c.501T>G）和 SNP3（c.918C>T）。对 30 名无精子症患者和 80 名正常妊娠证实的、有生育能力的男性进行了 HORMAD1 多态性分析。SNP1 和 SNP2 均与完全早期减数分裂停滞导致的人类无精子症相关（P<0.05）。我们认为，HORMAD1 在人类精子发生中具有重要的减数分裂功能。
