Evidence mapPaperPMID 42450625Full record

ReviewBiology2026

Trimethylamine N-Oxide and Impaired Spermatogenesis in the Gut-Testis Axis: A Focused Review of Current Evidence.

Xinyang Zhang, Jialin Luo, Xiang Zhang, Fang Yang, Xiaojin Zhang, Xujun Yu, Liang Dong

Abstract readReview
In one paragraph

Review in Biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Xinyang ZhangSchool of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Jialin LuoSchool of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Xiang ZhangSchool of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Fang YangSchool of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Xiaojin ZhangLibrary, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Xujun YuSchool of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Liang DongSchool of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Funding

China Postdoctoral Science Foundation No.2025M773939Science and Technology Department of Sichuan Province No. 2025ZNSFSC1798
6 · The paper itself

Abstract

Male infertility refers to the inability of a male partner to contribute to pregnancy after 12 months or more of regular unprotected intercourse. It is frequently associated with impaired spermatogenesis, and many cases cannot be completely explained by genetic, inflammatory, endocrine, or environmental factors. Trimethylamine N-oxide (TMAO) is generated when gut bacteria convert dietary choline, L-carnitine, and betaine into trimethylamine (TMA), which is oxidized in the liver mainly by flavin-containing monooxygenase 3 (FMO3). This focused review evaluates current evidence on TMAO and impaired spermatogenesis within the gut-testis axis. The rationale is biologically plausible because sperm motility depends on coordinated glycolytic and mitochondrial energy metabolism, whereas Leydig cell steroidogenesis depends on mitochondrial cholesterol transport and redox balance. Human observational studies associate TMAO with asthenozoospermia and Leydig cell-related markers, particularly insulin-like peptide 3 (INSL3), while mouse studies suggest testicular injury and reduced spermatogenesis after TMAO-related exposure. The Hippo/Yes-associated protein (YAP)-mitochondria-steroidogenic acute regulatory protein (StAR) axis has been proposed as one possible mechanism, but direct reproductive tract exposure, blood-testis barrier kinetics, and human validation remain unresolved. Overall, TMAO should be considered as a candidate metabolic mediator and not a proven causal factor or therapeutic target in male infertility.

Indexed as

asthenozoospermiagut microbiotagut–testis axisLeydig cellsoxidative stressspermatogenesistrimethylamine N-oxide

Identifiers

PMID42450625
PMCPMC13359403

What Socratic holds

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Registered trials

None linked

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 Socratic graph.