ArticleAmerican journal of human genetics2020
Bi-allelic DNAH8 Variants Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Primary Male Infertility.
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Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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89 citing papers in PubMed, 200 citations in OpenAlex.
- Biallelic Variants in ATP1A4 Are Associated with Oligoasthenoteratozoospermia and Male Infertility.Clinical genetics · 2026Article
- Application of Whole-Exome Sequencing in Identifying the Molecular Basis of Idiopathic Male Infertility.Journal of clinical medicine · 2026Review
- Biallelic loss-of-function variants in DNAH12 cause inner dynein arm defects and sperm head abnormalities leading to male infertility.Journal of assisted reproduction and genetics · 2026Article
- Biallelic loss-of-function variants in DNAH12 cause inner dynein arm defects and sperm head abnormalities leading to male infertility.Journal of assisted reproduction and genetics · 2026Article
- The potential role of dynein heavy chain genes in the pathophysiology of undescended testis.Pediatric surgery international · 2026Article
- Deficiency of primate-specific TFDP3 causes male infertility with oligoasthenoteratozoospermia in humans and cynomolgus monkeys.Science China. Life sciences · 2026Article
- A Testis-Specific Aralkylamine N-Acetyltransferase Regulates Dimorphic Sperm Function and Male Fertility in Moths.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNAH3 interacts with DNALI1 and is required for sperm flagellum function and male fertility.Reproductive biology and endocrinology : RB&E · 2026Article
- The intricate dance of RNA-binding proteins: unveiling the mechanisms behind male infertility.Human reproduction update · 2026Review
- Single-cell analysis of adult mouse testes exposed to cigarette smoke.Journal of assisted reproduction and genetics · 2026Article
- Mutations in CFAP57 disrupt the localization of MYH10 and IFT88, leading to flagellogenesis failure in humans and mice.Human genomics · 2025Article
- Reproductive physiological impacts of high ambient temperature on animals: the impaired testicular function and compromised sperm quality in C57BL/6 mice.Biological research · 2025Article
- Prenatal Low Testosterone Levels Induced byBiomedicines · 2025Article
- A novel frameshift variant in AXDND1 may cause multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family.Asian journal of andrology · 2025Article
- Of mice and men: translating mouse knockout models of human male infertility.Reproduction (Cambridge, England) · 2025Review
- How exome sequencing improves the diagnostics and management of men with non-syndromic infertility.Andrology · 2025Review
- Novel bi-allelic variants in DNAH10 lead to multiple morphological abnormalities of sperm flagella and male infertility.Asian journal of andrology · 2025Article
- Function of manchette and intra-manchette transport in spermatogenesis and male fertility.Cell communication and signaling : CCS · 2025Review
- Deficiency in DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice.eLife · 2025Article
- A novel homozygous splicing mutation in AK7 causes multiple morphological abnormalities of sperm flagella in patients from consanguineous Pakistani families.Asian journal of andrology · 2025Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 13 institutions in 3 countries.
Chunyu LiuObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China; State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211116, China.
Haruhiko MiyataResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Yang GaoReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China.
Yanwei ShaDepartment of Andrology, United Diagnostic and Research Center for Clinical Genetics, School of Public Health & Women and Children's Hospital, Xiamen University, Xiamen 361005, Fujian, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
Shuyan TangObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Zoulan XuResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
Marjorie WhitfieldINSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université de Paris, Paris 75014, France.
Catherine PatratINSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université de Paris, Paris 75014, France; Laboratoire d'Histologie Embryologie-Biologie de la Reproduction-CECOS Groupe Hospitalier Universitaire Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris 75014, France.
Huan WuReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China.
Emmanuel DulioustINSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université de Paris, Paris 75014, France; Laboratoire d'Histologie Embryologie-Biologie de la Reproduction-CECOS Groupe Hospitalier Universitaire Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris 75014, France.
Shixiong TianObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Keisuke ShimadaResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Jiangshan CongObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Taichi NodaResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Hang LiReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China.
Akane MorohoshiResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Caroline CazinTeam Genetics Epigenetics and Therapies of Infertility, Institute for Advanced Biosciences, Grenoble Alpes University (UGA), INSERM U1209, Centre National de la Recherche Scientifique UMR 5309, Grenoble 38000, France; UM de genetique de l'infertilite et de diagnostic pre-implantatoire (GI-DPI), Centre Hospitalier Universitaire Grenoble Alpes (CHUGA), Grenoble 38000, France; Service de Génétique, Laboratoire Eurofins Biomnis, Lyon, France.
Zine-Eddine KherrafTeam Genetics Epigenetics and Therapies of Infertility, Institute for Advanced Biosciences, Grenoble Alpes University (UGA), INSERM U1209, Centre National de la Recherche Scientifique UMR 5309, Grenoble 38000, France; UM de genetique de l'infertilite et de diagnostic pre-implantatoire (GI-DPI), Centre Hospitalier Universitaire Grenoble Alpes (CHUGA), Grenoble 38000, France.
Christophe ArnoultTeam Genetics Epigenetics and Therapies of Infertility, Institute for Advanced Biosciences, Grenoble Alpes University (UGA), INSERM U1209, Centre National de la Recherche Scientifique UMR 5309, Grenoble 38000, France.
Li JinObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China.
Xiaojin HeReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China.
Pierre F RayTeam Genetics Epigenetics and Therapies of Infertility, Institute for Advanced Biosciences, Grenoble Alpes University (UGA), INSERM U1209, Centre National de la Recherche Scientifique UMR 5309, Grenoble 38000, France; UM de genetique de l'infertilite et de diagnostic pre-implantatoire (GI-DPI), Centre Hospitalier Universitaire Grenoble Alpes (CHUGA), Grenoble 38000, France.
Yunxia CaoReproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei 230032, China.
Aminata TouréINSERM U1016, Institut Cochin, Paris 75014, France; Centre National de la Recherche Scientifique UMR8104, Paris 75014, France; Faculté de Médecine, Université de Paris, Paris 75014, France.
Feng ZhangObstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China; State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211116, China. Electronic address: zhangfeng@fudan.edu.cn.
Masahito IkawaResearch Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan; Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. Electronic address: ikawa@biken.osaka-u.ac.jp.
The University of Osaka · JPFudan University · CNInserm · FRAnhui Medical University · CNCentre National de la Recherche Scientifique · FRMinistry of Education of the People's Republic of China · CNShanghai Institute of Planned Parenthood Research · CNCentre de Gestion Scientifique · FRCentre Hospitalier Universitaire de Grenoble · FRFirst Affiliated Hospital of Anhui Medical University · CNOsaka University of Pharmaceutical Sciences · JPUniversité Grenoble Alpes · FRXiamen University · CN
Funding
Targeting sperm-specific proteins during meiosis and sperm morphogenesisP01HD087157 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI GARCIA, THOMAS · 2017 to 2021
$6.2MFunctional analysis of novel testis-expressed secreted and transmembrane proteinsR01HD088412 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI MARTIN M. MATZUK · 2016 to 2026
$4.5MNICHD NIH HHS P01 HD087157NICHD NIH HHS R01 HD088412
Abstract
Sperm malformation is a direct factor for male infertility. Multiple morphological abnormalities of the flagella (MMAF), a severe form of asthenoteratozoospermia, are characterized by immotile spermatozoa with malformed and/or absent flagella in the ejaculate. Previous studies indicated genetic heterogeneity in MMAF. To further define genetic factors underlying MMAF, we performed whole-exome sequencing in a cohort of 90 Chinese MMAF-affected men. Two cases (2.2%) were identified as carrying bi-allelic missense DNAH8 variants, variants which were either absent or rare in the control human population and were predicted to be deleterious by multiple bioinformatic tools. Re-analysis of exome data from a second cohort of 167 MMAF-affected men from France, Iran, and North Africa permitted the identification of an additional male carrying a DNAH8 homozygous frameshift variant. DNAH8 encodes a dynein axonemal heavy-chain component that is expressed preferentially in the testis. Hematoxylin-eosin staining and electron microscopy analyses of the spermatozoa from men harboring bi-allelic DNAH8 variants showed a highly aberrant morphology and ultrastructure of the sperm flagella. Immunofluorescence assays performed on the spermatozoa from men harboring bi-allelic DNAH8 variants revealed the absent or markedly reduced staining of DNAH8 and its associated protein DNAH17. Dnah8-knockout male mice also presented typical MMAF phenotypes and sterility. Interestingly, intracytoplasmic sperm injections using the spermatozoa from Dnah8-knockout male mice resulted in good pregnancy outcomes. Collectively, our experimental observations from humans and mice demonstrate that DNAH8 is essential for sperm flagellar formation and that bi-allelic deleterious DNAH8 variants lead to male infertility with MMAF.
Indexed as
Abnormalities, MultipleAllelesAnimalsAxonemal DyneinsCohort StudiesExomeExome SequencingFemaleFlagellaGenetic VariationHomozygoteHumansInfertility, MaleMaleMiceMice, KnockoutAxonemal DyneinsDnah8 protein, mouseCRISPRDNAH17DNAH8dyneinexomeflagellaICSIinfertilityknockoutsperm
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