Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes
Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosom...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2024-01-01
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| Series: | Asian Journal of Andrology |
| Subjects: | |
| Online Access: | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2024;volume=26;issue=1;spage=91;epage=98;aulast= |
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| author | Zhong-Mei Shao Yu-Tong Zhu Meng Gu Sen-Chao Guo Hui Yu Kuo-Kuo Li Dong-Dong Tang Yu-Ping Xu Ming-Rong Lv |
| author_facet | Zhong-Mei Shao Yu-Tong Zhu Meng Gu Sen-Chao Guo Hui Yu Kuo-Kuo Li Dong-Dong Tang Yu-Ping Xu Ming-Rong Lv |
| author_sort | Zhong-Mei Shao |
| collection | DOAJ |
| description | Variations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 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 DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 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. |
| first_indexed | 2024-03-07T23:01:20Z |
| format | Article |
| id | doaj.art-9ee94cfdd6b540feb2ddfa445da702c0 |
| institution | Directory Open Access Journal |
| issn | 1008-682X 1745-7262 |
| language | English |
| last_indexed | 2024-03-07T23:01:20Z |
| publishDate | 2024-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Asian Journal of Andrology |
| spelling | doaj.art-9ee94cfdd6b540feb2ddfa445da702c02024-02-22T14:40:20ZengWolters Kluwer Medknow PublicationsAsian Journal of Andrology1008-682X1745-72622024-01-01261919810.4103/aja202328Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomesZhong-Mei ShaoYu-Tong ZhuMeng GuSen-Chao GuoHui YuKuo-Kuo LiDong-Dong TangYu-Ping XuMing-Rong LvVariations in the dynein axonemal heavy chain gene, dynein axonemal heavy chain 6 (DNAH6), lead to multiple morphological abnormalities of the flagella. Recent studies have reported that these deficiencies may result in sperm head deformation. However, whether DNAH6 is also involved in human acrosome biogenesis remains unknown. The purpose of this study was to investigate DNAH6 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 DNAH6 among three unrelated families. The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants. Additionally, deficiencies in the acrosome, abnormal chromatin compaction, and vacuole-containing sperm heads were observed in these patients with DNAH6 variants. The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot. After intracytoplasmic sperm injection (ICSI) treatment, the partner of one patient with a DNAH6 variant achieved successful pregnancy. Overall, novel variants in DNAH6 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.http://www.ajandrology.com/article.asp?issn=1008-682X;year=2024;volume=26;issue=1;spage=91;epage=98;aulast=asthenoteratospermia; dnah6; intracytoplasmic sperm injection; male infertility |
| spellingShingle | Zhong-Mei Shao Yu-Tong Zhu Meng Gu Sen-Chao Guo Hui Yu Kuo-Kuo Li Dong-Dong Tang Yu-Ping Xu Ming-Rong Lv Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes Asian Journal of Andrology asthenoteratospermia; dnah6; intracytoplasmic sperm injection; male infertility |
| title | Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes |
| title_full | Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes |
| title_fullStr | Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes |
| title_full_unstemmed | Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes |
| title_short | Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella (MMAF) and ICSI outcomes |
| title_sort | novel variants in dnah6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella mmaf and icsi outcomes |
| topic | asthenoteratospermia; dnah6; intracytoplasmic sperm injection; male infertility |
| url | http://www.ajandrology.com/article.asp?issn=1008-682X;year=2024;volume=26;issue=1;spage=91;epage=98;aulast= |
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