{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T06:54:30Z","timestamp":1781506470464,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2702600"],"award-info":[{"award-number":["2022YFC2702600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402187"],"award-info":[{"award-number":["82402187"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"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>Oligoasthenoteratozoospermia (OAT), characterized by reduced sperm count, impaired motility, and abnormal morphology, is a major cause of male infertility with substantial genetic heterogeneity. However, the underlying genetic etiology remains unresolved in a large proportion of affected individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to identify novel genetic causes of human OAT and to investigate the molecular and clinical consequences of the identified variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Whole\u2010exome sequencing was performed in infertile men diagnosed with severe OAT. Identified variants were evaluated by population database screening and functional analyses, including quantitative mRNA assessment, label\u2010free proteomics, immunofluorescence staining, and transmission electron microscopy (TEM). Clinical outcomes following assisted reproductive treatment were also documented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified\n                      <jats:italic>CCDC189<\/jats:italic>\n                      as a novel pathogenic gene associated with human OAT. Two unrelated infertile men carried homozygous variants in\n                      <jats:italic>CCDC189<\/jats:italic>\n                      , including a frameshift variant (c.709_711del, p.W237Afs*3) and a missense variant (c.898C&gt;T, p.R300W), both of which were rare in population databases. Clinically, both individuals exhibited severe OAT with profound acrosomal abnormalities and multiple morphological defects of the sperm flagella. TEM analysis revealed acrosomal detachment, cytoplasmic retention, loss of radial spokes, and absence of the central pair complex, indicating severe disruption of axonemal architecture. Consistently,\n                      <jats:italic>CCDC189<\/jats:italic>\n                      mRNA levels were markedly reduced, and proteomic and immunofluorescence analyses confirmed the loss of CCDC189 protein along with its interacting partner CABCOCO1. Despite severe structural abnormalities, intracytoplasmic sperm injection (ICSI) using ejaculated sperm from one patient resulted in normal fertilization, high\u2010quality embryo development, and an ongoing clinical pregnancy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings establish\n                      <jats:italic>CCDC189<\/jats:italic>\n                      as a pathogenic gene underlying human OAT and expand the spectrum of coiled\u2010coil domain\u2013containing proteins essential for sperm morphogenesis. The favorable ICSI outcome underscores the clinical importance of genetic diagnosis in\n                      <jats:italic>CCDC189<\/jats:italic>\n                      \u2010related infertility and supports ICSI as an effective therapeutic option for affected couples.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70272","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T06:34:38Z","timestamp":1781505278000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss\u2010of\u2010Function Variants in\n                    <i>CCDC189<\/i>\n                    Cause Human Oligoasthenoteratozoospermia by Disrupting Sperm Flagellar and Acrosomal Architecture"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1127-749X","authenticated-orcid":false,"given":"Jianteng","family":"Zhou","sequence":"first","affiliation":[{"name":"Centre For Reproduction and Genetics Hefei National Research Center for Physical Sciences at the Microscale First Affiliated Hospital of USTC University of Science and Technology of China  Hefei China"},{"name":"Jiangsu Engineering Center For Precision Diagnosis and Treatment Research of Polygenic Diseases Department of Genetics Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghulam","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Centre For Reproduction and Genetics Hefei National Research Center for Physical Sciences at the Microscale First Affiliated Hospital of USTC University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Lin","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine Center For Reproductive Medicine Women and Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Clinical Research Center for Reproductive Medicine Chongqing Health Center For Women and Children  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Ye","sequence":"additional","affiliation":[{"name":"Centre For Reproduction and Genetics Hefei National Research Center for Physical Sciences at the Microscale First Affiliated Hospital of USTC University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Centre For Reproduction and Genetics Hefei National Research Center for Physical Sciences at the Microscale First Affiliated Hospital of USTC University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Centre For Reproduction and Genetics Hefei National Research Center for Physical Sciences at the Microscale First Affiliated Hospital of USTC University of Science and Technology of China  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Yang","sequence":"additional","affiliation":[{"name":"Jiangsu Engineering Center For Precision Diagnosis and Treatment Research of Polygenic Diseases Department of Genetics Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoning","family":"Huang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine Center For Reproductive Medicine Women and Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Clinical Research Center for Reproductive Medicine Chongqing Health Center For Women and Children  Chongqing 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