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Volume 25, Issue 3 (May 2023) 25, 398–403; 10.4103/aja202269

Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm

Juan Hua1, Lan Guo2, Yao Yao2, Wen Hu3, Yang-Yang Wan4, Bo Xu4

1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences; Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei 230032, China
    2 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China
    3 Hefei Xingzhike Biotechnology Co., Ltd., Hefei 230000, China
    4 Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China

Correspondence: Dr. YY Wan (wanyangyang1988@126.com) or Dr. B Xu (bio_xubo@163.com)



    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.
    Keywords: male infertility; tapered-head sperm; teratozoospermia; WD repeat domain 12 (WDR12)

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.