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

作　　者：Juan Hua Lan Guo Yao Yao Wen Hu Yang-Yang Wan Bo Xu 

机构地区：[1]Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Anhui Medical University,Hefei 230032,China [2]Metabolic Disease Research Center,School of Basic Medicine,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

出　　处：《Asian Journal of Andrology》2023年第3期398-403,共6页亚洲男性学杂志（英文版）

基　　金：This research was supported by the National Key Research and Development Project(No.2019YFA0802600);the National Natural Science Foundation of China(No.82101685,No.82171599,and No.81971333);2020 Basic and Clinical Cooperative Research Promotion Program of Anhui Medical University(No.2020xkjT014).

摘　　要：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.

关 键 词：male infertility tapered-head sperm TERATOZOOSPERMIA WD repeat domain 12(WDR12) 

分 类 号：R697[医药卫生—泌尿科学]