Evidence mapPaperPMID 41465073Full record

ReviewGenes2025

Sperm-Derived Extracellular Vesicles (Sperm-EVs), Emerging Biomarkers and Functional Modulators in Male Infertility and Assisted Reproduction.

Charalampos Voros, Fotios Chatzinikolaou, Georgios Papadimas, Spyridon Polykalas, Despoina Mavrogianni, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Vasiliki Kanaka, Maria Kanaka, Kyriakos Bananis and 11 more

Abstract readReview
In one paragraph

Review in Genes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

21 authors.

Charalampos Voros1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.ORCID 0000-0001-9477-7619
Fotios ChatzinikolaouLaboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, 54124 Athens, Greece.
Georgios PapadimasAthens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece.
Spyridon PolykalasAthens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece.
Despoina Mavrogianni1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.ORCID 0000-0003-1220-6594
Aristotelis-Marios Koulakmanidis1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.
Diamantis AthanasiouIVF Athens Reproduction Center, 15123 Maroussi, Greece.
Vasiliki Kanaka1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.
Maria Kanaka1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.
Kyriakos BananisKing's College Hospitals NHS Foundation Trust, London SE5 9RS, UK.ORCID 0000-0001-7563-4305
Antonia AthanasiouIVF Athens Reproduction Center, 15123 Maroussi, Greece.
Aikaterini AthanasiouIVF Athens Reproduction Center, 15123 Maroussi, Greece.
Ioannis PapapanagiotouAthens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece.ORCID 0000-0002-9723-5054
Dimitrios VaitsisAthens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece.
Charalampos Tsimpoukelis1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.
Maria Anastasia Daskalaki1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.
Marianna Theodora1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.ORCID 0000-0001-8280-7796
Nikolaos Thomakos1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.
Panagiotis Antsaklis1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.ORCID 0000-0003-2106-5922
Dimitrios LoutradisLaboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, 54124 Athens, Greece.ORCID 0000-0002-8686-594X
Georgios Daskalakis1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.ORCID 0000-0001-7108-211X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

objectivesApproximately 50% of infertility cases are attributable to male factors; yet conventional semen examination can not identify the molecular abnormalities that hinder sperm functionality. Extracellular vesicles (EVs) derived from sperm, such as testicular EVs, prostasomes, and epididymosomes, have become important modulators of oocyte activation, sperm maturation, capacitation, acrosome stability, motility, and early embryonic development. This study aimed to evaluate the potential diagnostic and translational uses of sperm-associated extracellular vesicles (EVs) in male infertility and assisted reproduction, while also consolidating recent insights on their origins, composition, and functional significance.

methodsA focused narrative search of PubMed (2000-2025) was conducted using backward and forward citation tracking. Studies that qualified included human clinical cohorts, functional sperm extracellular vesicle tests, and omics analyses using MISEV-aligned extracellular vesicle isolation and characterisation methodologies. When human mechanistic understanding was constrained, knowledge from animal research was selectively integrated.

resultsThe cargo signatures specific to the source identified in sperm-derived and seminal EVs encompass proteins, small RNAs, lipids, and enzymatic modules that govern sperm maturation, capacitation, acrosome reaction, redox balance, calcium signalling, zona binding, and DNA integrity. Density-resolved seminal extracellular vesicle subfractions (EV-H/EV-M/EV-L) have unique functional and proteomic characteristics linked to progesterone-induced hyperactivation, oxidative stress, and motility. Asthenozoospermia and oligoasthenoteratozoospermia are associated with changes in extracellular vesicle composition, reduced embryonic developmental potential, compromised oocyte activation (related to PLCζ), and increased sperm DNA fragmentation. Numerous EV-related miRNA and protein signatures may predict TESE results, identify functional sperm anomalies not recognised by conventional semen analysis, and differentiate between obstructive and non-obstructive azoospermia.

conclusionsThe available findings indicate that sperm-derived extracellular vesicles are significant functional regulators of sperm physiology and may serve as valuable non-invasive indicators for male infertility. The standardisation of EV isolation, characterisation, and clinical validation is essential prior to widespread use; nonetheless, their integration into liquid biopsy methods and assisted reproductive technology processes represents a significant improvement.

Indexed as

Extracellular VesiclesInfertility, MaleSpermatozoaAnimalsBiomarkersHumansMaleReproductive Techniques, AssistedBiomarkersacrosome reactionassisted reproductioncapacitationepididymosomesmale infertilityprostasomessperm extracellular vesiclessperm small RNAs

Identifiers

PMID41465073
PMCPMC12732803

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.