ORIGINAL RESEARCH article

Front. Mol. Biosci.

Sec. Metabolomics

Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1578998

This article is part of the Research TopicAdvances on Molecular Mechanisms Regulating Reproduction - From Gametogenesis to FertilizationView all 4 articles

Untargeted Metabolomics Fingerprints in Seminal Plasma of Patients with Abnormal Sperm Morphology using High-Performance Liquid Chromatography and Mass Spectrometry

Provisionally accepted
Serena CorrentiSerena Correnti1Giuseppina FanelliGiuseppina Fanelli2Mariaimmacolata Preiano'Mariaimmacolata Preiano'1*Veronica LelliVeronica Lelli2Mariagrazia TarantinoMariagrazia Tarantino3Annalisa FregolaAnnalisa Fregola4Massimo BitontiMassimo Bitonti4Emanuela ChiarellaEmanuela Chiarella3Anna Maria TimperioAnna Maria Timperio2Sara RinalducciSara Rinalducci2Rocco SavinoRocco Savino5Rosa TerraccianoRosa Terracciano3
  • 1Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Calabria, Italy
  • 2Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Lazio, Italy
  • 3Department of Clinical and Experimental Medicine, Magna Græcia University of Catanzaro, Catanzaro, Calabria, Italy
  • 4Urogyn Biotech S. R. L., Catanzaro, Italy., CATANZARO, Italy
  • 5Department of Medical and Surgical Science, University of Magna Graecia, Catanzaro, Calabria, Italy

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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.

Keywords: male infertility, Human seminal plasma, Teratozoospermia, Mass Spectrometry, Metabolomics, biomarkers, Reproductive Medicine, precision medicine

Received: 18 Feb 2025; Accepted: 30 May 2025.

Copyright: © 2025 Correnti, Fanelli, Preiano', Lelli, Tarantino, Fregola, Bitonti, Chiarella, Timperio, Rinalducci, Savino and Terracciano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mariaimmacolata Preiano', Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, 88100, Calabria, Italy

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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