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Asian Journal of Andrology (2012) 14, 580-583; doi:10.1038/aja.2011.180; published online 12 March 2012
Single-nucleotide polymorphisms in HORMAD1 may be a risk factor for azoospermia caused by meiotic arrest in Japanese patients
Toshinobu Miyamoto1, Akira Tsujimura2, Yasushi Miyagawa2, Eitetsu Koh3, Mikio Namiki3, Michiharu Horikawa1, Yasuaki Saijo4 and Kazuo Sengoku1
1 Department of Obstetrics and Gynecology, Asahikawa Medical University, Asahikawa, Hokkaido 078-8510, Japan
2 Department of Urology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
3 Department of Integrated Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-1192, Japan
4 Division of Community Medicine and Epidemiology, Department of Health Science, Asahikawa Medical University, Asahikawa 078-8510, Japan
Correspondence: Dr T Miyamoto, (toshim@asahikawa-med.ac.jp)
Received 18 September 2011; Revised 22 October 2011; Accepted 8 December 2011
Advance online publication 12 March 2012.
| Abstract |
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.
Keywords: azoospermia; HORMAD1; male infertility; male meiosis; SNP |
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