Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm
作者机构：Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesAnhui Medical UniversityHefei 230032China Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefei 230032China Hefei Xingzhike Biotechnology Co.Ltd.Hefei 230000China Reproductive and Genetic HospitalThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China
出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)
年 卷 期：2023年第25卷第3期
页 面：398-403页
核心收录：
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).
主 题：male infertility tapered-head sperm teratozoospermia WD repeat domain 12(WDR12)
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.484TG)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.484TG)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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