{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:32:56Z","timestamp":1791361976904,"version":"4.3.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>\n                    Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (\n                    <jats:italic toggle=\"yes\">DNAH6<\/jats:italic>\n                    ), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether\n                    <jats:italic toggle=\"yes\">DNAH6<\/jats:italic>\n                    is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate\n                    <jats:italic toggle=\"yes\">DNAH6<\/jats:italic>\n                    gene variants and their potential functions in the formation of defective sperm heads and flagella. Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University (Hefei, China). Hematoxylin and eosin staining, scanning electron microscopy, and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure. Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants. We identified three novel deleterious variants in\n                    <jats:italic toggle=\"yes\">DNAH6<\/jats:italic>\n                    among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with\n                    <jats:italic toggle=\"yes\">DNAH6<\/jats:italic>\n                    variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with\n                    <jats:italic toggle=\"yes\">DNAH6<\/jats:italic>\n                    variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with\n                    <jats:italic toggle=\"yes\">DNAH6<\/jats:italic>\n                    variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a\n                    <jats:italic toggle=\"yes\">DNAH6<\/jats:italic>\n                    variant achieved successful pregnancy. Overall, novel variants in\n                    <jats:italic toggle=\"yes\">DNAH6<\/jats:italic>\n                    genes that contribute to defects in the sperm head and flagella were identified, and the findings indicated ICSI as an effective clinical treatment for such patients.\n                  <\/jats:p>","DOI":"10.4103\/aja202328","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T11:59:52Z","timestamp":1691582392000},"page":"91-98","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":27,"title":["Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes"],"prefix":"10.4103","volume":"26","author":[{"given":"Zhong-Mei","family":"Shao","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Department of Obstetrics and Gynecology, Fuyang Hospital of Anhui Medical University, Fuyang 236112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Tong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People\u2019s Republic of China, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Gu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People\u2019s Republic of China, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen-Chao","family":"Guo","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People\u2019s Republic of China, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Department of Obstetrics and Gynecology, Fuyang Hospital of Anhui Medical University, Fuyang 236112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Kuo","family":"Li","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People\u2019s Republic of China, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Dong","family":"Tang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People\u2019s Republic of China, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ping","family":"Xu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People\u2019s Republic of China, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Rong","family":"Lv","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China"},{"name":"Department of Obstetrics and Gynecology, Fuyang Hospital of Anhui Medical University, Fuyang 236112, China"},{"name":"NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei 230032, China"},{"name":"Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People\u2019s Republic of China, Hefei 230032, 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