{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:38:12Z","timestamp":1792827492033,"version":"4.5.0"},"reference-count":19,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["xzy012023127"],"award-info":[{"award-number":["xzy012023127"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Experimental disruption of\n Zpbp<\/jats:italic>\n homologs in mice causes defective acrosomal biogenesis and male infertility. Human evidence remains limited to a small number of association\u2010based or case\u2010level reports linking\n ZPBP<\/jats:italic>\n alterations to abnormal sperm\u2010head or acrosomal phenotypes, without integrated characterization across protein abundance, ultrastructure, sperm chromatin integrity, and proteome\u2010wide changes.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n Our study aimed to characterize the genetic, structural, and molecular sperm phenotype associated with a novel homozygous frameshift variant in\n ZPBP<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n Whole\u2010exome sequencing (WES) and Sanger sequencing were performed in the proband. Semen parameters, Papanicolaou\u2010stained morphology, and FITC\u2010PSA\u2010defined acrosomal staining patterns were assessed. ZPBP protein abundance was evaluated by Western blotting. Sperm morphology and ultrastructure were examined by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Sperm chromatin structure assay, IZUMO1 immunofluorescence, and label\u2010free proteomic profiling were also performed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A man born to consanguineous parents carried a novel homozygous frameshift variant in\n ZPBP<\/jats:italic>\n (NM_007009.3:c.421_422del; p.Phe141Profs*4), classified as a variant of uncertain significance; parental samples were unavailable for segregation analysis. The proband had normal sperm concentration but markedly reduced motility and complete absence of morphologically normal spermatozoa, with predominantly head abnormalities, consistent with severe asthenoteratozoospermia. Head, midpiece, and principal\u2010piece abnormalities occurred in 99.33%\u00a0\u00b1\u00a00.47%, 14.67%\u00a0\u00b1\u00a02.62%, and 22.67%\u00a0\u00b1\u00a03.40% of spermatozoa, respectively. Abnormal, fragmented, or absent FITC\u2010PSA staining was observed in 84.33%\u00a0\u00b1\u00a01.70%. Western blotting demonstrated absence of ZPBP protein in patient sperm. SEM and TEM showed complete or partial acrosomal loss, membrane and matrix fragmentation, widening of the subacrosomal space, and nuclear\u2010acrosomal detachment. The DNA fragmentation index was 52.25% and high DNA stainability was 5.71%. IZUMO1 staining was markedly reduced or absent in the proband's sperm. Proteomic profiling showed coordinated lower abundance of multiple acrosome\u2010related proteins and negative enrichment of acrosomal pathways.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion and conclusion<\/jats:title>\n \n The findings associate the novel homozygous\n ZPBP<\/jats:italic>\n frameshift variant with severe acrosomal structural abnormalities, impaired acrosomal integrity, and broader sperm\u2010head molecular disruption. The abnormal FITC\u2010PSA pattern is not interpreted as direct evidence of spontaneous or premature acrosome exocytosis. Detailed acrosomal and sperm\u2010morphology phenotyping may support genetic diagnosis and counseling, but this case provides no direct evidence regarding fertilization competence or the optimal assisted\u2010reproduction strategy for the proband's own sperm.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/andr.70395","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:04:53Z","timestamp":1792825493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Homozygous\n ZPBP<\/i>\n Frameshift Variant Is Associated With Severe Acrosomal Structural Abnormalities in Asthenoteratozoospermia"],"prefix":"10.1111","author":[{"given":"Jie","family":"Yang","sequence":"first","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3898-2115","authenticated-orcid":false,"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7760-0723","authenticated-orcid":false,"given":"Huan","family":"Ren","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0704-7210","authenticated-orcid":false,"given":"Shengjia","family":"Shi","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0239-6670","authenticated-orcid":false,"given":"Junyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center School of Medicine Shanghai First Maternity and Infant Hospital Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjun","family":"Ding","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine in Gansu Provincial Maternity and Child\u2010Care Hospital, Gansu Provincial Central Hospital Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5673-5247","authenticated-orcid":false,"given":"Zhifeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center Renmin Hospital, Hubei University of Medicine Shiyan Hubei China"},{"name":"Hubei Clinical Research Center for Reproductive Medicine Shiyan Hubei China"},{"name":"Shiyan Key Laboratory of Reproduction and Genetics, Renmin Hospital Hubei University of Medicine Shiyan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanzi","family":"Shi","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3897-6838","authenticated-orcid":false,"given":"Sen","family":"Qiao","sequence":"additional","affiliation":[{"name":"Reproductive Center Northwest Women's and Children's Hospital Xi'an Shaanxi 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