Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm
Teratozoospermia is a rare disease associated with male infertility. Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology, but the genetic basis of tapered-head sperm is not well understood. In this study, whole-exome sequencing (WES) identified a ho...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Asian Journal of Andrology |
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| Online Access: | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2023;volume=25;issue=3;spage=398;epage=403;aulast= |
| _version_ | 1797824464971366400 |
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| author | Juan Hua Lan Guo Yao Yao Wen Hu Yang-Yang Wan Bo Xu |
| author_facet | Juan Hua Lan Guo Yao Yao Wen Hu Yang-Yang Wan Bo Xu |
| author_sort | Juan Hua |
| collection | DOAJ |
| description | Teratozoospermia is a rare disease associated with male infertility. Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology, but the genetic basis of tapered-head sperm is not well understood. In this study, whole-exome sequencing (WES) identified a homozygous WD repeat domain 12 (WDR12; p.Ser162Ala/c.484T>G) variant in an infertile patient with tapered-head spermatozoa from a consanguineous Chinese family. Bioinformatic analysis predicted this mutation to be a pathogenic variant. To verify the effect of this variant, we analyzed WDR12 protein expression in spermatozoa of the patient and a control individual, as well as in the 293T cell line, by Western blot analysis, and found that WDR12 expression was significantly downregulated. To understand the role of normal WDR12, we evaluated its mRNA and protein expression in mice at different ages. We observed that WDR12 expression was increased in pachytene spermatocytes, with intense staining visible in round spermatid nuclei. Based on these results, the data suggest that the rare biallelic pathogenic missense variant (p.Ser162Ala/c.484T>G) in the WDR12 gene is associated with tapered-head spermatozoa. In addition, after intracytoplasmic sperm injection (ICSI), a successful pregnancy was achieved. This finding indicates that infertility associated with this WDR12 homozygous mutation can be overcome by ICSI. The present results may provide novel insights into understanding the molecular mechanisms of male infertility. |
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| id | doaj.art-c8fac589f447480499fc992757214521 |
| institution | Directory Open Access Journal |
| issn | 1008-682X 1745-7262 |
| language | English |
| last_indexed | 2024-03-13T10:39:22Z |
| publishDate | 2023-01-01 |
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| series | Asian Journal of Andrology |
| spelling | doaj.art-c8fac589f447480499fc9927572145212023-05-18T04:59:34ZengWolters Kluwer Medknow PublicationsAsian Journal of Andrology1008-682X1745-72622023-01-0125339840310.4103/aja202269Biallelic mutations in WDR12 are associated with male infertility with tapered-head spermJuan HuaLan GuoYao YaoWen HuYang-Yang WanBo XuTeratozoospermia is a rare disease associated with male infertility. Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology, but the genetic basis of tapered-head sperm is not well understood. In this study, whole-exome sequencing (WES) identified a homozygous WD repeat domain 12 (WDR12; p.Ser162Ala/c.484T>G) variant in an infertile patient with tapered-head spermatozoa from a consanguineous Chinese family. Bioinformatic analysis predicted this mutation to be a pathogenic variant. To verify the effect of this variant, we analyzed WDR12 protein expression in spermatozoa of the patient and a control individual, as well as in the 293T cell line, by Western blot analysis, and found that WDR12 expression was significantly downregulated. To understand the role of normal WDR12, we evaluated its mRNA and protein expression in mice at different ages. We observed that WDR12 expression was increased in pachytene spermatocytes, with intense staining visible in round spermatid nuclei. Based on these results, the data suggest that the rare biallelic pathogenic missense variant (p.Ser162Ala/c.484T>G) in the WDR12 gene is associated with tapered-head spermatozoa. In addition, after intracytoplasmic sperm injection (ICSI), a successful pregnancy was achieved. This finding indicates that infertility associated with this WDR12 homozygous mutation can be overcome by ICSI. The present results may provide novel insights into understanding the molecular mechanisms of male infertility.http://www.ajandrology.com/article.asp?issn=1008-682X;year=2023;volume=25;issue=3;spage=398;epage=403;aulast=male infertility; tapered-head sperm; teratozoospermia; wd repeat domain 12 (wdr12) |
| spellingShingle | Juan Hua Lan Guo Yao Yao Wen Hu Yang-Yang Wan Bo Xu Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm Asian Journal of Andrology male infertility; tapered-head sperm; teratozoospermia; wd repeat domain 12 (wdr12) |
| title | Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm |
| title_full | Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm |
| title_fullStr | Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm |
| title_full_unstemmed | Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm |
| title_short | Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm |
| title_sort | biallelic mutations in wdr12 are associated with male infertility with tapered head sperm |
| topic | male infertility; tapered-head sperm; teratozoospermia; wd repeat domain 12 (wdr12) |
| url | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2023;volume=25;issue=3;spage=398;epage=403;aulast= |
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