{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T20:41:30Z","timestamp":1786653690298,"version":"build-2736575974"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>\n                    Genetic variants in the dynein axonemal heavy chain 17 (\n                    <jats:italic toggle=\"yes\">DNAH17<\/jats:italic>\n                    ) have been implicated in multiple morphological abnormalities of the sperm flagella (MMAF) and asthenoteratozoospermia (ATZS). The aim of this study is to identify novel\n                    <jats:italic toggle=\"yes\">DNAH17<\/jats:italic>\n                    variants associated with MMAF and ATZS and to evaluate the impact of these variants on sperm motility, sperm morphology, the ultrastructure of sperm flagella, and the outcomes of intracytoplasmic sperm injection (ICSI). In the present study, we identified one novel homozygous and three compound heterozygous\n                    <jats:italic toggle=\"yes\">DNAH17<\/jats:italic>\n                    variants in one consanguineous and three nonconsanguineous families. Semen analysis revealed significant reductions in sperm motility and notable morphological changes. Transmission electron microscopy (TEM) revealed the absence of outer dynein arms (ODAs), loss of peripheral doublet microtubules (DMTs) 4\u20137, and multiple mitochondrial sheath (MS) abnormalities in the sperm flagella. Functional analyses indicated that these variants disrupted the expression and localization of the\n                    <jats:italic toggle=\"yes\">DNAH17<\/jats:italic>\n                    protein in the sperm flagella. Tandem mass tagging proteomics and immunofluorescence demonstrated a significant reduction in the expression of proteins associated with the assembly of ODA-associated proteins into the axoneme from individuals with DNAH17 variants. Notably, successful pregnancies were achieved through ICSI combined with assisted oocyte activation (AOA) treatment in the female partner of these probands. This study identified seven novel homozygous or compound heterozygous\n                    <jats:italic toggle=\"yes\">DNAH17<\/jats:italic>\n                    variants in both consanguineous and nonconsanguineous families, highlighting their detrimental effects on sperm motility, morphology, and flagellar ultrastructure. These findings provide valuable insights for the genetic diagnosis of MMAF and may enhance future genetic counseling strategies.\n                  <\/jats:p>","DOI":"10.4103\/aja202567","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:00:09Z","timestamp":1768802409000},"page":"427-436","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Novel homozygous or compound heterozygous DNAH17 variants lead to male infertility characterized by multiple morphological abnormalities of the sperm flagella and asthenoteratozoospermia in humans"],"prefix":"10.4103","volume":"28","author":[{"given":"Jie","family":"Yang","sequence":"first","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Nan","family":"Gu","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xue","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, AmCare Genomics Lab, Guangzhou 510005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Qiao","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Jia","family":"Shi","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"R1-20260702","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41572-023-00459-w","article-title":"Male infertility","volume":"9","author":"Eisenberg","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"R2-20260702","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1007\/s10815-024-03274-8","article-title":"Genetic etiological spectrum of sperm 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outcomes","volume":"42","author":"Dai","year":"2025","journal-title":"J Assist Reprod Genet"},{"key":"R6-20260702","doi-asserted-by":"crossref","first-page":"91","DOI":"10.4103\/aja202328","article-title":"Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes","volume":"26","author":"Shao","year":"2024","journal-title":"Asian J Androl"},{"key":"R7-20260702","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.gene.2017.08.033","article-title":"A homozygous CEP135 mutation is associated with multiple morphological abnormalities of the sperm flagella (MMAF)","volume":"633","author":"Sha","year":"2017","journal-title":"Gene"},{"key":"R8-20260702","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s10815-024-03139-0","article-title":"Identification of a novel CFAP61 homozygous splicing variant associated with multiple morphological abnormalities of the 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History"}},{"value":"2025-08-05","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}