Evidence map›Paper›PMID 40707433›Full record

ArticleCell death discovery2025

The RNF8/OPTN/KDM6A axis controls macrophage polarization to maintain testicular microenvironment homeostasis.

Yanan Guo, Peng Xia, Yixiao Tian, Daosen Fu, Xiaohui Hu, Kun Xie, Wenhao Dong, Wei Zhang, Disheng Liu, Rong Shen and 1 more

Abstract read
In one paragraph

Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yanan GuoSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.ORCID http://orcid.org/0000-0003-0311-361X
Peng XiaSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
Yixiao TianSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
Daosen FuSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
Xiaohui HuSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
Kun XieSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
Wenhao DongSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
Wei ZhangReproductive Medicine Center, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu, China.
Disheng LiuDepartment of Urology, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu, China.
Rong ShenSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China. shenr@lzu.edu.cn.ORCID http://orcid.org/0000-0002-7155-1876
Degui WangSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China. wangdegui@lzu.edu.cn.ORCID http://orcid.org/0000-0001-9923-2060

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82071695National Natural Science Foundation of China (National Science Foundation of China) 82203630National Natural Science Foundation of China (National Science Foundation of China) 82471640
6 · The paper itself

Abstract

Dysregulated immune responses may erroneously target normal reproductive tissues, thereby compromising the proper functioning of the reproductive system. Macrophages are the most abundant immune cells in the testes, however, the role of macrophages in spermatogenic function is not yet clear. This study indicated that the increase of pro-inflammatory macrophages impaired the development of spermatogenic cells, and the deficiency of RNF8 led to a proinflammatory state in the testicular microenvironment and diminished sperm production in mice. RNF8 mainly assembled K63-branched ubiquitin chains on autophagy receptor OPTN at K448 thus causing OPTN activation. The increased ubiquitination of OPTN promoted degradation of KDM6A via the autophagy-lysosome pathway, thereby inhibiting macrophage polarization towards the pro-inflammatory type and maintaining an immune privilege state in the testicular microenvironment. This homeostasis could be collapsed once the RNF8-OPTN-KDM6A axis was abnormal, subsequently resulting in remodeling of the testicular microenvironment. This study reveals the underlying mechanism of RNF8 on male reproduction, and the pro-inflammatory microenvironment resulting from RNF8 deficiency hindered spermatogenic cell differentiation, thereby impairing spermatogenic function.

Identifiers

PMID40707433
PMCPMC12289966

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.