{"title":"Establishing the causative link between CFAP221 variants and asthenoteratozoospermia in humans.","authors":"Gan Shen, Erpo Tian, Chuan Jiang, Yunchuan Tian, Yingteng Zhang, Xiang Wang, Jiang Gu, Ying Shen, Fei Geng","doi":"10.1007/s10815-025-03472-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To identify the novel genetic causes of male infertility related to asthenoteratozoospermia in two unrelated Chinese families.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) and sanger sequencing were performed on peripheral blood samples from two infertile patients' families. Papanicolaou stain, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) revealed the morphology and ultrastructure of the infertile patients' spermatozoon. Immunofluorescence staining and single-cell RNA sequencing analysis identified the expression of CFAP221 in the different stages of spermatogenesis sperm cells in mouse and human testes. Bioinformatics analysis predicted the protein interactions involving CFAP221.</p><p><strong>Results: </strong>Pathogenic biallelic variants in CFAP221 were detected in two unrelated infertile men by whole-exome sequencing. Abnormalities in the morphology and ultrastructure of sperm flagella were detected in the two patients. Moreover, during the spermatogenesis, CFAP221 was primarily localized in the flagella of elongating and elongated sperm in humans and mice. Bioinformatics analysis predicted that CFAP221 interacts with flagellum development related proteins such as CFAP74, CFAP194, CFAP246, and CFAP297, and is co-expressed with these proteins in various spermatids during mouse spermatogenesis. Furthermore, intracytoplasmic sperm injection (ICSI) treatment can rescue male infertility caused by harmful variants in CFAP221.</p><p><strong>Conclusion: </strong>Our findings suggested that CFAP221 is a novel causative gene for male infertility and our findings would guide clinical ICSI treatment and diagnosis of male infertility.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"1975-1987"},"PeriodicalIF":2.7000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229367/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Assisted Reproduction and Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10815-025-03472-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/24 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: To identify the novel genetic causes of male infertility related to asthenoteratozoospermia in two unrelated Chinese families.
Methods: Whole-exome sequencing (WES) and sanger sequencing were performed on peripheral blood samples from two infertile patients' families. Papanicolaou stain, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) revealed the morphology and ultrastructure of the infertile patients' spermatozoon. Immunofluorescence staining and single-cell RNA sequencing analysis identified the expression of CFAP221 in the different stages of spermatogenesis sperm cells in mouse and human testes. Bioinformatics analysis predicted the protein interactions involving CFAP221.
Results: Pathogenic biallelic variants in CFAP221 were detected in two unrelated infertile men by whole-exome sequencing. Abnormalities in the morphology and ultrastructure of sperm flagella were detected in the two patients. Moreover, during the spermatogenesis, CFAP221 was primarily localized in the flagella of elongating and elongated sperm in humans and mice. Bioinformatics analysis predicted that CFAP221 interacts with flagellum development related proteins such as CFAP74, CFAP194, CFAP246, and CFAP297, and is co-expressed with these proteins in various spermatids during mouse spermatogenesis. Furthermore, intracytoplasmic sperm injection (ICSI) treatment can rescue male infertility caused by harmful variants in CFAP221.
Conclusion: Our findings suggested that CFAP221 is a novel causative gene for male infertility and our findings would guide clinical ICSI treatment and diagnosis of male infertility.
期刊介绍：
The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species.
The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.
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