{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T19:59:17Z","timestamp":1784145557648,"version":"3.55.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Male infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, we identified biallelic mutations of <jats:italic>CEP70<\/jats:italic> in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in <jats:italic>Cep70<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying <jats:italic>CEP70<\/jats:italic> variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Biallelic mutations of <jats:italic>CEP70<\/jats:italic> might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1133222","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T16:42:18Z","timestamp":1678380138000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification of biallelic variations of CEP70 in patients with male infertility"],"prefix":"10.3389","volume":"14","author":[{"given":"Tiechao","family":"Ruan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male Infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet (London England)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.clinbiochem.2018.03.012","article-title":"Fertility and infertility: Definition and epidemiology","volume":"62","author":"Vander Borght","year":"2018","journal-title":"Clin Biochem"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv016","article-title":"Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century","volume":"21","author":"Inhorn","year":"2015","journal-title":"Hum Reprod update"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30040-7","article-title":"Novel concepts in the aetiology of male reproductive impairment","volume":"5","author":"Tournaye","year":"2017","journal-title":"Lancet Diabetes endocrinology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2010.08.006","article-title":"Male Infertility: Pathogenesis and clinical diagnosis","volume":"25","author":"Krausz","year":"2011","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-018-0003-3","article-title":"Genetics of male infertility","volume":"15","author":"Krausz","year":"2018","journal-title":"Nat Rev Urology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/humupd\/dmab030","article-title":"A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships","volume":"28","author":"Houston","year":"2021","journal-title":"Hum Reprod update"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00709-013-0488-9","article-title":"CEP proteins: the knights of centrosome dynasty","volume":"250","author":"Kumar","year":"2013","journal-title":"Protoplasma>"},{"key":"B9","doi-asserted-by":"publisher","first-page":"110987","DOI":"10.1016\/j.mce.2020.110987","article-title":"The sperm centrioles","volume":"518","author":"Avidor-Reiss","year":"2020","journal-title":"Mol Cell endocrinology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1038\/s41467-022-29109-7","article-title":"CEP128 is involved in spermatogenesis in humans and mice","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.stem.2018.08.007","article-title":"Single-cell RNA sequencing analysis reveals sequential cell fate transition during human spermatogenesis","volume":"23","author":"Wang","year":"2018","journal-title":"Cell Stem Cell"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M112.020552","article-title":"Human sperm tail proteome suggests new endogenous metabolic pathways","volume":"12","author":"Amaral","year":"2013","journal-title":"Mol Cell Proteomics MCP"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nature02166","article-title":"Proteomic characterization of the human centrosome by protein correlation profiling","volume":"426","author":"Andersen","year":"2003","journal-title":"Nature>"},{"key":"B14","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/s41419-021-03755-z","article-title":"Loss of CEP70 function affects acrosome biogenesis and flagella formation during spermiogenesis","volume":"12","author":"Liu","year":"2021","journal-title":"Cell Death disease"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/cells7070067","article-title":"Rapid evolution of sperm produces diverse centriole structures that reveal the most rudimentary structure needed for function","volume":"7","author":"Avidor-Reiss","year":"2018","journal-title":"Cells"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13662","article-title":"Loss-of-function mutations in centrosomal protein 112 is associated with human acephalic spermatozoa phenotype","volume":"97","author":"Sha","year":"2020","journal-title":"Clin Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.gene.2017.08.033","article-title":"A homozygous CEP135 mutation is associated with multiple morphological abnormalities of the sperm flagella (MMAF)","volume":"633","author":"Sha","year":"2017","journal-title":"Gene>"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn0968","article-title":"Loss-of-function mutations in CEP78 cause male infertility in humans and mice","volume":"8","author":"Zhang","year":"2022","journal-title":"Sci Adv"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gms017","article-title":"Cep70 promotes microtubule assembly in vitro by increasing microtubule elongation","volume":"44","author":"Shi","year":"2012","journal-title":"Acta Biochim Biophys Sinica"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.06.017","article-title":"Cep70 regulates microtubule stability by interacting with HDAC6","volume":"589","author":"Shi","year":"2015","journal-title":"FEBS letters"},{"key":"B21","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1471-2121-10-17","article-title":"Cep70 and Cep131 contribute to ciliogenesis in zebrafish embryos","volume":"10","author":"Wilkinson","year":"2009","journal-title":"BMC Cell Biol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1133222\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T16:42:21Z","timestamp":1678380141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1133222\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":21,"alternative-id":["10.3389\/fendo.2023.1133222"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1133222","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,9]]},"article-number":"1133222"}}