{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:29:38Z","timestamp":1790616578747,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32000587"],"award-info":[{"award-number":["32000587"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31890780"],"award-info":[{"award-number":["31890780"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32061143006"],"award-info":[{"award-number":["32061143006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-obstructive azoospermia (NOA), characterized by spermatogenesis failure and the absence of sperm in ejaculation, is the most severe form of male infertility. However, the etiology and pathology between meiosis-associated monogenic alterations and human NOA remain largely unknown. A homozygous MSH5 mutation (c.1126del) was identified from two idiopathic NOA patients in the consanguineous family. This mutation led to the degradation of MSH5 mRNA and abolished chromosome axial localization of MutS\u03b3 in spermatocytes from the affected males. Chromosomal spreading analysis of the patient\u2019s meiotic prophase I revealed that the meiosis progression was arrested at a zygotene-like stage with extensive failure of homologous synapsis and DSB repair. Therefore, our study demonstrates that the MSH5 c.1126del could cause meiotic recombination failure and lead to human infertility, improving the genetic diagnosis of NOA clinically. Furthermore, the study of human spermatocytes elucidates the meiosis defects caused by MSH5 variant, and reveals a conserved and indispensable role of MutS\u03b3 in human synapsis and meiotic recombination, which have not previously been well-described.<\/jats:p>","DOI":"10.3390\/ijms23126522","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T09:26:48Z","timestamp":1655026008000},"page":"6522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Homozygous Loss-of-Function Mutation in MSH5 Abolishes MutS\u03b3 Axial Loading and Causes Meiotic Arrest in NOA-Affected Individuals"],"prefix":"10.3390","volume":"23","author":[{"given":"Chenjia","family":"Gong","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei 230001, China"},{"name":"The CAS Key Laboratory 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1180-9799","authenticated-orcid":false,"given":"Qinghua","family":"Shi","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of University of Science and Technology of China, University of Science and Technology of China, Hefei 230001, China"},{"name":"The CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei 230027, China"},{"name":"School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"},{"name":"Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei 230027, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12958-015-0032-1","article-title":"A unique view on male infertility around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod. 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