Unraveling the Multi-Omic Landscape of Extracellular Vesicles in Human Seminal Plasma

Extracellular Vesicles (EVs) from seminal plasma have achieved attention due to their potential physiopathological role in male reproductive systems. This study employed a comprehensive proteomic and transcriptomic approach to investigate the composition and molecular signatures of EVs isolated from...

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Main Authors: Laura Governini, Alesandro Haxhiu, Enxhi Shaba, Lorenza Vantaggiato, Alessia Mori, Marco Bruttini, Francesca Loria, Natasa Zarovni, Paola Piomboni, Claudia Landi, Alice Luddi
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Language:English
Published: MDPI AG 2025-06-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/6/836
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author Laura Governini
Alesandro Haxhiu
Enxhi Shaba
Lorenza Vantaggiato
Alessia Mori
Marco Bruttini
Francesca Loria
Natasa Zarovni
Paola Piomboni
Claudia Landi
Alice Luddi
author_facet Laura Governini
Alesandro Haxhiu
Enxhi Shaba
Lorenza Vantaggiato
Alessia Mori
Marco Bruttini
Francesca Loria
Natasa Zarovni
Paola Piomboni
Claudia Landi
Alice Luddi
author_sort Laura Governini
collection DOAJ
description Extracellular Vesicles (EVs) from seminal plasma have achieved attention due to their potential physiopathological role in male reproductive systems. This study employed a comprehensive proteomic and transcriptomic approach to investigate the composition and molecular signatures of EVs isolated from human seminal plasma. EVs from Normozoospermic (NORMO), OligoAsthenoTeratozoospermic (OAT), and Azoospermic (AZO) subjects were isolated using a modified polymer precipitation-based protocol and characterized for size and morphology. Comprehensive proteomic analysis, using both gel-free and gel-based approaches, revealed distinct protein profiles in each group (<i>p</i><0.01), highlighting potential molecules and pathways involved in sperm function and fertility. The data are available via ProteomeXchange with identifiers PXD051361 and PXD051390, respectively. Transcriptomic analysis confirmed the trend of a general downregulation of AZO and OAT compared to NORMO shedding light on regulatory mechanisms of sperm development. Bioinformatic tools were applied for functional omics analysis; the integration of proteomic and transcriptomic data provided a comprehensive understanding of the cargo content and regulatory networks present in EVs. This study contributes to elucidating the key role of EVs in the paracrine communication regulating spermatogenesis. A full understanding of these pathways not only suggests potential mechanisms regulating male fertility but also offers new insights into the development of diagnostic tools targeting male reproductive disorders.
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spelling doaj-art-2ffeec9313974ad9bb4acdce2fb3a4332025-08-20T02:24:42ZengMDPI AGBiomolecules2218-273X2025-06-0115683610.3390/biom15060836Unraveling the Multi-Omic Landscape of Extracellular Vesicles in Human Seminal PlasmaLaura Governini0Alesandro Haxhiu1Enxhi Shaba2Lorenza Vantaggiato3Alessia Mori4Marco Bruttini5Francesca Loria6Natasa Zarovni7Paola Piomboni8Claudia Landi9Alice Luddi10Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyFunctional Proteomics Lab, Department of Life Sciences, University of Siena, 53100 Siena, ItalyFunctional Proteomics Lab, Department of Life Sciences, University of Siena, 53100 Siena, ItalyTuscany Centre for Precision Medicine (CReMeP), Department of Medicine Surgery and Neurosciences, University of Siena, 53100 Siena, ItalyTuscany Centre for Precision Medicine (CReMeP), Department of Medicine Surgery and Neurosciences, University of Siena, 53100 Siena, ItalyHansaBioMed Life Sciences Ltd., 12618 Tallinn, EstoniaHansaBioMed Life Sciences Ltd., 12618 Tallinn, EstoniaDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyFunctional Proteomics Lab, Department of Life Sciences, University of Siena, 53100 Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, 53100 Siena, ItalyExtracellular Vesicles (EVs) from seminal plasma have achieved attention due to their potential physiopathological role in male reproductive systems. This study employed a comprehensive proteomic and transcriptomic approach to investigate the composition and molecular signatures of EVs isolated from human seminal plasma. EVs from Normozoospermic (NORMO), OligoAsthenoTeratozoospermic (OAT), and Azoospermic (AZO) subjects were isolated using a modified polymer precipitation-based protocol and characterized for size and morphology. Comprehensive proteomic analysis, using both gel-free and gel-based approaches, revealed distinct protein profiles in each group (<i>p</i><0.01), highlighting potential molecules and pathways involved in sperm function and fertility. The data are available via ProteomeXchange with identifiers PXD051361 and PXD051390, respectively. Transcriptomic analysis confirmed the trend of a general downregulation of AZO and OAT compared to NORMO shedding light on regulatory mechanisms of sperm development. Bioinformatic tools were applied for functional omics analysis; the integration of proteomic and transcriptomic data provided a comprehensive understanding of the cargo content and regulatory networks present in EVs. This study contributes to elucidating the key role of EVs in the paracrine communication regulating spermatogenesis. A full understanding of these pathways not only suggests potential mechanisms regulating male fertility but also offers new insights into the development of diagnostic tools targeting male reproductive disorders.https://www.mdpi.com/2218-273X/15/6/836extracellular vesiclesseminal plasmamale reproductive tractreproductionintercellular communicationproteomics
spellingShingle Laura Governini
Alesandro Haxhiu
Enxhi Shaba
Lorenza Vantaggiato
Alessia Mori
Marco Bruttini
Francesca Loria
Natasa Zarovni
Paola Piomboni
Claudia Landi
Alice Luddi
Unraveling the Multi-Omic Landscape of Extracellular Vesicles in Human Seminal Plasma
Biomolecules
extracellular vesicles
seminal plasma
male reproductive tract
reproduction
intercellular communication
proteomics
title Unraveling the Multi-Omic Landscape of Extracellular Vesicles in Human Seminal Plasma
title_full Unraveling the Multi-Omic Landscape of Extracellular Vesicles in Human Seminal Plasma
title_fullStr Unraveling the Multi-Omic Landscape of Extracellular Vesicles in Human Seminal Plasma
title_full_unstemmed Unraveling the Multi-Omic Landscape of Extracellular Vesicles in Human Seminal Plasma
title_short Unraveling the Multi-Omic Landscape of Extracellular Vesicles in Human Seminal Plasma
title_sort unraveling the multi omic landscape of extracellular vesicles in human seminal plasma
topic extracellular vesicles
seminal plasma
male reproductive tract
reproduction
intercellular communication
proteomics
url https://www.mdpi.com/2218-273X/15/6/836
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