{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:08:16Z","timestamp":1789549696827,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Macrozoospermia is a rare form of teratozoospermia characterized by tetraploids, large\u2010headed spermatozoa with multiple flagella, usually caused by bi\u2010allelic\n                      <jats:italic>AURKC<\/jats:italic>\n                      mutations. The etiology of atypical phenotypes with a lower proportion of large headed spermatozoa and single flagella however often remains unresolved.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the genetic cause of severe sperm\u2010head abnormalities with moderate macrozoospermia without multiflagellated spermatozoa in a patient with repeated ICSI failure. An infertile male with three failed ICSI attempts underwent semen analysis, revealing complete teratozoospermia, including 25% macrocephalic spermatozoa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Multi\u2010probe FISH targeting chromosomes 13, 18, 21, X, Y assessed chromosomal segregation. Whole\u2010exome sequencing (WES) was performed to identify a candidate variant associated with meiotic abnormalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FISH analysis revealed a high proportion of spermatozoa with n (23) chromosomes and 2c DNA content, consistent with sister chromatid non\u2010disjunction during meiosis II. WES identified a homozygous missense variation in\n                      <jats:italic>CCNA1<\/jats:italic>\n                      , coding for a protein described to be essential for meiotic progression and chromatin remodeling in male germ cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      The variant affects a highly conserved residue within a functional domain and is predicted to be deleterious. This study establishes the first clinical association between\n                      <jats:italic>CCNA1<\/jats:italic>\n                      mutations and chromatid non\u2010disjunction in human spermatogenesis. It highlights the limitations of current morphology\u2010based diagnostic thresholds and supports cytogenetic and genomic assessment for severe teratozoospermia (especially head abnormalities) and ART failure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Expanding genetic screening panels to include\n                      <jats:italic>CCNA1<\/jats:italic>\n                      may improve diagnostic precision and clinical management in atypical macrozoospermia cases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70387","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:41:33Z","timestamp":1789548093000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A CCNA1 Missense Variant Associated With Chromatid Non\u2010Disjunction in Abnormal\u2010Headed Sperm and Male Infertility"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5354-762X","authenticated-orcid":false,"given":"Aurore","family":"Perrin","sequence":"first","affiliation":[{"name":"Inserm, EFS, UMR1078, GGB Brest University  Brest France"},{"name":"Service De G\u00e9n\u00e9tique M\u00e9dicale Et De Biologie De La reproduction, CHU Brest  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-2477","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Morel","sequence":"additional","affiliation":[{"name":"Inserm, EFS, UMR1078, GGB Brest University  Brest France"},{"name":"Service De G\u00e9n\u00e9tique M\u00e9dicale Et De Biologie De La reproduction, CHU Brest  Brest 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