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The RNF8/OPTN/KDM6A axis controls macrophage polarization to maintain testicular microenvironment homeostasis
Yanan Guo1, Peng Xia1, Yixiao Tian1
1School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
Cell Death Discovery
|July 24, 2025
Summary
RNF8 deficiency causes inflammation in testes, impairing sperm production. This occurs because RNF8 normally prevents pro-inflammatory macrophages, maintaining male reproductive health.
Area of Science:
- Reproductive Immunology
- Molecular Biology
- Cellular Biology
Background:
- Immune responses can disrupt reproductive tissues.
- Macrophages are key immune cells in testes, but their role in spermatogenesis is unclear.
Purpose of the Study:
- To investigate the role of RNF8 in testicular immune privilege and spermatogenesis.
- To elucidate the molecular mechanism by which RNF8 influences macrophage polarization and sperm production.
Main Methods:
- Mice models were used to study the effects of RNF8 deficiency.
- Immunohistochemistry and molecular assays were employed to analyze testicular microenvironment and cell function.
Main Results:
- RNF8 deficiency led to a pro-inflammatory testicular environment and reduced sperm production in mice.
- RNF8 deficiency impaired spermatogenic cell development and differentiation.
- RNF8 activates the autophagy receptor OPTN, promoting KDM6A degradation and inhibiting pro-inflammatory macrophage polarization.
Conclusions:
- RNF8 is crucial for maintaining immune privilege in the testes by regulating macrophage polarization via the RNF8-OPTN-KDM6A axis.
- Dysregulation of this axis due to RNF8 deficiency compromises male reproductive function by promoting inflammation and hindering spermatogenesis.
