System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ppublish 5 citations

PubMed: 39142440 DOI: 10.1016/j.jare.2024.08.011

An essential role of the E3 ubiquitin ligase RNF126 in ensuring meiosis I completion during spermatogenesis.

J Adv Res 73:231-245

Authors: Wenjing Liu, Xiya Sun, Fubing Li, Qiuyun Jiang, Jianting An, Yingying Wu, Jingyi Yang, Meng Qin, Yuxin Zhao, Yongjia Tang, Tingyue Wu, Zhiqiang Yan, Dewei Jiang, Rong Liu, Wenhui Li, Xu Zhi, Ceshi Chen

Affiliations

  • The Third Affiliated Hospital, Kunming Medical University, Kunming 650118, China; Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China; Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China.
  • State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China.
  • Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China.
  • Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China.
  • State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  • Department of the Pathology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
  • The Third Affiliated Hospital, Kunming Medical University, Kunming 650118, China.
  • Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China; Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310063, China.
  • The Third Affiliated Hospital, Kunming Medical University, Kunming 650118, China; Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China.

Abstract

INTRODUCTION

Homologous recombination repair during meiosis is essential for the exchange of genetic information between sister chromosomes, underpinning spermatogenesis and, consequently, fertility. The disruption of this process can lead to infertility, highlighting the importance of identifying the molecular actors involved.

OBJECTIVES

This study aims to elucidate the role of the E3 ubiquitin ligase Rnf126 in spermatogenesis and its impact on fertility, particularly through its involvement in meiotic homologous recombination repair.

METHODS

We used heterozygous and homozygous Rnf126 deletion models in mouse testes to examine the consequences on testicular health, sperm count, and the process of spermatogenesis. Additionally, we explored the association between RNF126 gene missense variants and nonobstructive male infertility in patients, with a focus on their functional impact on the protein's ubiquitin ligase activity.

RESULTS

Rnf126 deletion led to testicular atrophy, disrupted seminiferous tubule structure, reduced sperm count, and spermatogenesis arrest at meiotic prophase I. Furthermore, male mice exhibited impaired homologous recombination repair and increased apoptosis within the seminiferous tubules. We identified four missense variants of the RNF126 (V68M, R241H, E261A, D253N) associated with male infertility. Specifically, the E261A and D253N variants, located in the RING domain, directly compromised the E3 ubiquitin ligase activity of RNF126.

CONCLUSION

Our findings demonstrate the pivotal role of RNF126 in maintaining spermatogenesis and fertility, offering insights into the molecular mechanisms underlying male infertility. The identified RNF126 variants present novel targets for diagnostic and therapeutic strategies in treating nonobstructive male infertility.

MeSH

Ligases, Genes, Recombination, Genetic, Fertility, Ubiquitin, Homologous Recombination, Infertility, Sperm Count, Seminiferous Tubules, Recombinational Dna Repair, Meiotic Prophase I, Infertility, Male, Ubiquitin-Protein Ligases, Spermatogenesis, Spermatozoa, Meiosis

Cited by