Single-nucleotide polymorphisms in the human RAD21L gene may be a genetic risk factor for Japanese patients with azoospermia caused by meiotic arrest and Sertoli cell-only syndrome

Abstract

Genetic mechanisms are implicated in some cases of male infertility. Recently, it was demonstrated that male mice lacking the gene for RAD21L exhibited azoospermia caused by meiotic arrest. Mouse RAD21L is a functionally relevant meiotic α-kleisin that is essential for male fertility. Therefore, we hypothesized that RAD21L mutations or polymorphisms may be associated with male infertility, especially azoospermia secondary to meiotic arrest. To determine if RAD21L defects are associated with azoospermia in groups of patients with meiotic arrest, we performed direct sequencing of the RAD21L coding regions in 38 Japanese patients with meiotic arrest and in 200 normal controls. Three coding single-nucleotide polymorphisms (SNP1–SNP3) were detected in the meiotic arrest patient group. Sertoli cell-only syndrome is considered a common cause of non-obstructive azoospermia. For comparison, the RAD21L coding regions in which SNP1–SNP3 were detected were sequenced in 140 patients with Sertoli cell-only syndrome. Statistical analyses were used to compare the two groups of patients with the control group. Genotype and allele frequencies of SNP2 and SNP3 were notably higher in the two patient groups compared with the control group (Bonferroni adjusted p value <0.016). These results suggest a critical role for RAD21L in human spermatogenesis.

Keywords:

• Azoospermia
• meiotic arrest
• RAD21L
• SCOS
• single-nucleotide polymorphism

Acknowledgements

This work was supported by Grants-in-Aid from the Suhara Memorial Foundation; Scientific Research (Nos. 25462547, 26462469 and 24249019) from the Japan Society for the Promotion of Science; grants from the Ministry of Health, Labour and Welfare, Japan; the Strategic Research Program for Brain Sciences (No. 11105137) and by a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (No. 12024421).

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by Grants-in-Aid from the Suhara Memorial Foundation; Scientific Research [Nos. 25462547, 26462469 and 24249019] from the Japan Society for the Promotion of Science; grants from the Ministry of Health, Labour and Welfare, Japan; the Strategic Research Program for Brain Sciences [No. 11105137] and by a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan [No. 12024421].