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

## TL;DR

This study uses advanced chemical analysis to identify metabolic differences in seminal fluid from men with abnormal sperm shape, pointing to potential biomarkers for infertility.

## Contribution

The study identifies 14 altered metabolites in teratozoospermia, including O-acetyl-L-serine, and links them to inflammation, oxidative stress, and DNA damage.

## Key findings

- 14 metabolites were significantly altered in teratozoospermic samples compared to normozoospermic samples.
- O-acetyl-L-serine, Creatine, and Histidine showed strong discriminatory power as potential biomarkers.
- Metabolic changes suggest inflammation, oxidative stress, and DNA damage in teratozoospermia.

## Abstract

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.