Untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high-performance liquid chromatography and mass spectrometry

Teratozoospermia, a qualitative sperm disorder characterized by abnormal sperm morphology, represents one of the causes of male infertility worldwide. The metabolic analysis of human seminal plasma (SP), can provide insights into the underlying molecular mechanisms of this condition, identifying nov...

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Main Authors: Serena Correnti, Giuseppina Fanelli, Mariaimmacolata Preianò, Veronica Lelli, Mariagrazia Tarantino, Annalisa Fregola, Massimo Bitonti, Emanuela Chiarella, Anna Maria Timperio, Sara Rinalducci, Rocco Savino, Rosa Terracciano
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Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Molecular Biosciences
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Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2025.1578998/full
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author Serena Correnti
Giuseppina Fanelli
Mariaimmacolata Preianò
Veronica Lelli
Mariagrazia Tarantino
Annalisa Fregola
Massimo Bitonti
Emanuela Chiarella
Anna Maria Timperio
Sara Rinalducci
Rocco Savino
Rosa Terracciano
author_facet Serena Correnti
Giuseppina Fanelli
Mariaimmacolata Preianò
Veronica Lelli
Mariagrazia Tarantino
Annalisa Fregola
Massimo Bitonti
Emanuela Chiarella
Anna Maria Timperio
Sara Rinalducci
Rocco Savino
Rosa Terracciano
author_sort Serena Correnti
collection DOAJ
description Teratozoospermia, a qualitative sperm disorder characterized by abnormal sperm morphology, represents one of the causes of male infertility worldwide. The metabolic analysis of human seminal plasma (SP), can provide insights into the underlying molecular mechanisms of this condition, identifying novel biomarkers and facilitating the development of diagnostic tests. In this study, an untargeted High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) approach was performed to explore SP metabolic alterations associated with teratozoospermia. SP samples from 15 teratozoospermic (TZ) vs. 20 normozoospermic (NZ) subjects were analyzed to identify metabolic pathways linked to sperm morphology dysfunction. Multivariate statistical analysis, including Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal PLS-DA, revealed a distinct separation between TZ and NZ, highlighting 14 significantly altered metabolites. Based on Variable Importance in Projection scores, O-acetyl-L-serine showed the highest score. Main findings include alterations in Creatine, Histidine, Adenine, Allantoin and Deoxyuridine levels, suggesting perturbations in inflammation, oxidative stress and sperm DNA damage in teratozoospermia. Correlation and Receiver Operating Characteristic (ROC) analyses identified potential biomarkers, including O-acetyl-L-serine, Creatine, and Histidine, with robust discriminatory power (AUC >0.7). These findings highlight potential metabolic pathways implicated in the pathophysiology of teratozoospermia and provide a foundation for enabling personalized patient management with precision treatment.
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spelling doaj-art-5a3a82617baa4bf2b259f860adadb1f52025-08-20T03:31:24ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-06-011210.3389/fmolb.2025.15789981578998Untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high-performance liquid chromatography and mass spectrometrySerena Correnti0Giuseppina Fanelli1Mariaimmacolata Preianò2Veronica Lelli3Mariagrazia Tarantino4Annalisa Fregola5Massimo Bitonti6Emanuela Chiarella7Anna Maria Timperio8Sara Rinalducci9Rocco Savino10Rosa Terracciano11Department of Health Sciences, Magna Græcia University, Catanzaro, ItalyDepartment of Ecological and Biological Sciences (DEB), University of Tuscia, Viterbo, ItalyDepartment of Health Sciences, Magna Græcia University, Catanzaro, ItalyDepartment of Ecological and Biological Sciences (DEB), University of Tuscia, Viterbo, ItalyDepartment of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, ItalyUrogyn Biotech S. R. L., Catanzaro, ItalyUrogyn Biotech S. R. L., Catanzaro, ItalyDepartment of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, ItalyDepartment of Ecological and Biological Sciences (DEB), University of Tuscia, Viterbo, ItalyDepartment of Ecological and Biological Sciences (DEB), University of Tuscia, Viterbo, ItalyDepartment of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, ItalyDepartment of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, ItalyTeratozoospermia, a qualitative sperm disorder characterized by abnormal sperm morphology, represents one of the causes of male infertility worldwide. The metabolic analysis of human seminal plasma (SP), can provide insights into the underlying molecular mechanisms of this condition, identifying novel biomarkers and facilitating the development of diagnostic tests. In this study, an untargeted High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) approach was performed to explore SP metabolic alterations associated with teratozoospermia. SP samples from 15 teratozoospermic (TZ) vs. 20 normozoospermic (NZ) subjects were analyzed to identify metabolic pathways linked to sperm morphology dysfunction. Multivariate statistical analysis, including Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal PLS-DA, revealed a distinct separation between TZ and NZ, highlighting 14 significantly altered metabolites. Based on Variable Importance in Projection scores, O-acetyl-L-serine showed the highest score. Main findings include alterations in Creatine, Histidine, Adenine, Allantoin and Deoxyuridine levels, suggesting perturbations in inflammation, oxidative stress and sperm DNA damage in teratozoospermia. Correlation and Receiver Operating Characteristic (ROC) analyses identified potential biomarkers, including O-acetyl-L-serine, Creatine, and Histidine, with robust discriminatory power (AUC >0.7). These findings highlight potential metabolic pathways implicated in the pathophysiology of teratozoospermia and provide a foundation for enabling personalized patient management with precision treatment.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1578998/fullmale infertilityhuman seminal plasmateratozoospermiamass spectrometrymetabolomicsbiomarkers
spellingShingle Serena Correnti
Giuseppina Fanelli
Mariaimmacolata Preianò
Veronica Lelli
Mariagrazia Tarantino
Annalisa Fregola
Massimo Bitonti
Emanuela Chiarella
Anna Maria Timperio
Sara Rinalducci
Rocco Savino
Rosa Terracciano
Untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high-performance liquid chromatography and mass spectrometry
Frontiers in Molecular Biosciences
male infertility
human seminal plasma
teratozoospermia
mass spectrometry
metabolomics
biomarkers
title Untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high-performance liquid chromatography and mass spectrometry
title_full Untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high-performance liquid chromatography and mass spectrometry
title_fullStr Untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high-performance liquid chromatography and mass spectrometry
title_full_unstemmed Untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high-performance liquid chromatography and mass spectrometry
title_short Untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high-performance liquid chromatography and mass spectrometry
title_sort untargeted metabolomics fingerprints in seminal plasma of patients with abnormal sperm morphology using high performance liquid chromatography and mass spectrometry
topic male infertility
human seminal plasma
teratozoospermia
mass spectrometry
metabolomics
biomarkers
url https://www.frontiersin.org/articles/10.3389/fmolb.2025.1578998/full
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