Age-related elevation of O-GlcNAc causes meiotic arrest in male mice
Abstract In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-lin...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-05-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01433-x |
| _version_ | 1797823005527638016 |
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| author | Zhang Qian Chuwei Li Shanmeizi Zhao Hong Zhang Rujun Ma Xie Ge Jun Jing Li Chen Jinzhao Ma Yang Yang Lu Zheng Kemei Zhang Zhaowanyue He Mengqi Xue Ying Lin Kadiliya Jueraitetibaike Yuming Feng Chun Cao Ting Tang Shanshan Sun Hui Teng Wei Zhao Bing Yao |
| author_facet | Zhang Qian Chuwei Li Shanmeizi Zhao Hong Zhang Rujun Ma Xie Ge Jun Jing Li Chen Jinzhao Ma Yang Yang Lu Zheng Kemei Zhang Zhaowanyue He Mengqi Xue Ying Lin Kadiliya Jueraitetibaike Yuming Feng Chun Cao Ting Tang Shanshan Sun Hui Teng Wei Zhao Bing Yao |
| author_sort | Zhang Qian |
| collection | DOAJ |
| description | Abstract In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging. |
| first_indexed | 2024-03-13T10:17:26Z |
| format | Article |
| id | doaj.art-3bfd2810a194454e8624f7a294335cba |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-13T10:17:26Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-3bfd2810a194454e8624f7a294335cba2023-05-21T11:08:49ZengNature Publishing GroupCell Death Discovery2058-77162023-05-019111110.1038/s41420-023-01433-xAge-related elevation of O-GlcNAc causes meiotic arrest in male miceZhang Qian0Chuwei Li1Shanmeizi Zhao2Hong Zhang3Rujun Ma4Xie Ge5Jun Jing6Li Chen7Jinzhao Ma8Yang Yang9Lu Zheng10Kemei Zhang11Zhaowanyue He12Mengqi Xue13Ying Lin14Kadiliya Jueraitetibaike15Yuming Feng16Chun Cao17Ting Tang18Shanshan Sun19Hui Teng20Wei Zhao21Bing Yao22Center of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Nanjing Jinling Hospital, Nanjing Medical UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityBasic Medical Laboratory, Nanjing Jinling Hospital, Clinical School of Medical College, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Nanjing Jinling Hospital, Nanjing Medical UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Nanjing Jinling Hospital, Nanjing Medical UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityJiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal UniversityCenter of Reproductive Medicine, Nanjing Jinling Hospital, Nanjing Medical UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityCenter of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing UniversityAbstract In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.https://doi.org/10.1038/s41420-023-01433-x |
| spellingShingle | Zhang Qian Chuwei Li Shanmeizi Zhao Hong Zhang Rujun Ma Xie Ge Jun Jing Li Chen Jinzhao Ma Yang Yang Lu Zheng Kemei Zhang Zhaowanyue He Mengqi Xue Ying Lin Kadiliya Jueraitetibaike Yuming Feng Chun Cao Ting Tang Shanshan Sun Hui Teng Wei Zhao Bing Yao Age-related elevation of O-GlcNAc causes meiotic arrest in male mice Cell Death Discovery |
| title | Age-related elevation of O-GlcNAc causes meiotic arrest in male mice |
| title_full | Age-related elevation of O-GlcNAc causes meiotic arrest in male mice |
| title_fullStr | Age-related elevation of O-GlcNAc causes meiotic arrest in male mice |
| title_full_unstemmed | Age-related elevation of O-GlcNAc causes meiotic arrest in male mice |
| title_short | Age-related elevation of O-GlcNAc causes meiotic arrest in male mice |
| title_sort | age related elevation of o glcnac causes meiotic arrest in male mice |
| url | https://doi.org/10.1038/s41420-023-01433-x |
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