2. Academic Validation
  3. Age-related elevation of O-GlcNAc causes meiotic arrest in male mice

Age-related elevation of O-GlcNAc causes meiotic arrest in male mice

  • Cell Death Discov. 2023 May 15;9(1):163. doi: 10.1038/s41420-023-01433-x.
Zhang Qian # 1,  Chuwei Li # 1,  Shanmeizi Zhao # 2,  Hong Zhang 1,  Rujun Ma 1,  Xie Ge 1,  Jun Jing 3,  Li Chen 1,  Jinzhao Ma 1,  Yang Yang 4,  Lu Zheng 1,  Kemei Zhang 3,  Zhaowanyue He 1,  Mengqi Xue 3,  Ying Lin 1,  Kadiliya Jueraitetibaike 1,  Yuming Feng 1,  Chun Cao 1,  Ting Tang 1,  Shanshan Sun 2,  Hui Teng 3,  Wei Zhao 5,  Bing Yao 6
Affiliations

Affiliations

  • 1 Center of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, 210002, Jiangsu, China.
  • 2 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, China.
  • 3 Center of Reproductive Medicine, Nanjing Jinling Hospital, Nanjing Medical University, Nanjing, 210002, China.
  • 4 Basic Medical Laboratory, Nanjing Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, 210002, Jiangsu, China.
  • 5 Center of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, 210002, Jiangsu, China. zhaowei0714@nicemice.cn.
  • 6 Center of Reproductive Medicine, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, 210002, Jiangsu, China. yaobing@nju.edu.
  • # Contributed equally.
PMID: 37188682 DOI: 10.1038/s41420-023-01433-x
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.

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