{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:43:36Z","timestamp":1788446616384,"version":"build-2803163510"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 (\n                    <jats:italic toggle=\"yes\">CFAP300<\/jats:italic>\n                    ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous\n                    <jats:italic toggle=\"yes\">CFAP300<\/jats:italic>\n                    loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in\n                    <jats:italic toggle=\"yes\">CFAP300<\/jats:italic>\n                    -mutant individual, whereas immunofluorescence demonstrated markedly reduced\n                    <jats:italic toggle=\"yes\">CFAP300<\/jats:italic>\n                    expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the\n                    <jats:italic toggle=\"yes\">CFAP300<\/jats:italic>\n                    mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband\u2019s sperm. Overall, this study expands the known\n                    <jats:italic toggle=\"yes\">CFAP300<\/jats:italic>\n                    mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.\n                  <\/jats:p>","DOI":"10.4103\/aja202556","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T07:00:15Z","timestamp":1756882815000},"page":"743-750","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["CFAP300 loss-of-function variant causes primary ciliary dyskinesia and male infertility via disrupting sperm flagellar assembly and acrosome formation"],"prefix":"10.4103","volume":"27","author":[{"given":"Hua-Yan","family":"Yin","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Qi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun-Shan","family":"Shen","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China"},{"name":"Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Ru","family":"Li","sequence":"additional","affiliation":[{"name":"The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China"},{"name":"Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Xia","family":"Cao","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China"},{"name":"Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Guo","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Song","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei 230032, China"},{"name":"Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"R1-20251103","doi-asserted-by":"crossref","first-page":"F1000","DOI":"10.12688\/f1000research.17076.1","article-title":"Recent advances in understanding and managing male infertility","volume":"8","author":"Fainberg","year":"2019","journal-title":"F1000 Res"},{"key":"R2-20251103","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.advms.2019.12.008","article-title":"Proven and unproven methods for diagnosis and treatment of infertility","volume":"65","author":"Szamatowicz","year":"2020","journal-title":"Adv Med 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