Evidence map›Paper›PMID 40331931›Full record

ReviewInternational journal of molecular sciences2025

Interplay of Ferroptosis, Cuproptosis, Autophagy and Pyroptosis in Male Infertility: Molecular Crossroads and Therapeutic Opportunities.

Difan Cai, Junda Li, Zekang Peng, Rong Fu, Chuyang Chen, Feihong Liu, Yiwang Li, Yanjing Su, Chunyun Li, Wei Chen

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

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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

10 authors.

Difan CaiHealth Science Center, Hunan Normal University, Changsha 410013, China.
Junda LiHealth Science Center, Hunan Normal University, Changsha 410013, China.
Zekang PengHealth Science Center, Hunan Normal University, Changsha 410013, China.
Rong FuHealth Science Center, Hunan Normal University, Changsha 410013, China.ORCID 0009-0006-2910-0832
Chuyang ChenHealth Science Center, Hunan Normal University, Changsha 410013, China.
Feihong LiuHealth Science Center, Hunan Normal University, Changsha 410013, China.
Yiwang LiHealth Science Center, Hunan Normal University, Changsha 410013, China.
Yanjing SuHealth Science Center, Hunan Normal University, Changsha 410013, China.
Chunyun LiHealth Science Center, Hunan Normal University, Changsha 410013, China.
Wei ChenHealth Science Center, Hunan Normal University, Changsha 410013, China.ORCID 0000-0002-0634-8150

Funding

Hunan Province College Students Research Learning and Innovative Experiment Project S202310542141Natural Science Foundation of Hunan Province 2023JJ30424Natural Science Foundation of Hunan Province 2024JJ5284Scientific Research Project of the Hunan Provincial Department of Education 24C0023
6 · The paper itself

Abstract

Male infertility is intricately linked to dysregulated cell death pathways, including ferroptosis, cuproptosis, pyroptosis, and autophagy. Ferroptosis, driven by iron-dependent lipid peroxidation through the Fenton reaction and inactivation of the GPX4/Nrf2/SLC7A11 axis, disrupts spermatogenesis under conditions of oxidative stress, environmental toxin exposure, or metabolic disorders. Similarly, cuproptosis-characterized by mitochondrial dysfunction and disulfide stress due to copper overload-exacerbates germ cell apoptosis via FDX1 activation and NADPH depletion. Pyroptosis, mediated by the NLRP3 inflammasome and gasdermin D, amplifies testicular inflammation and germ cell loss via IL-1β/IL-18 release, particularly in response to environmental insults. Autophagy maintains testicular homeostasis by clearing damaged organelles and proteins; however, its dysregulation impairs sperm maturation and compromises blood-testis barrier integrity. These pathways intersect through shared regulators; reactive oxygen species and mTOR modulate the autophagy-pyroptosis balance, while Nrf2 and FDX1 bridge ferroptosis-cuproptosis crosstalk. Therapeutic interventions targeting these mechanisms have shown promise in preclinical models. However, challenges persist, including the tissue-specific roles of gasdermin isoforms, off-target effects of pharmacological inhibitors, and transgenerational epigenetic impacts of environmental toxins. This review synthesizes current molecular insights into the cell death pathways implicated in male infertility, emphasizing their interplay and translational potential for restoring spermatogenic function.

Indexed as

AutophagyFerroptosisInfertility, MalePyroptosisAnimalsHumansMaleSpermatogenesisautophagycuproptosisferroptosismale infertilitypyroptosis

Identifiers

PMID40331931
PMCPMC12026609

What OpenQuestion holds

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Read underepoch 390

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 OpenQuestion graph.