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Targeted Amino Acids Profiling of Human Seminal Plasma from Teratozoospermia Patients Using LC–MS/MS

  • Reproductive Endocrinology: Original Article
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Abstract

Identifying the metabolome of human seminal plasma (HSP) is a new research area to screen putative biomarkers of infertility. This case–control study was performed on HSP specimens of 15 infertile patients with teratozoospermia (defined as normal sperm morphology < 4%) and 12 confirmed fertile normozoospermic men as the control group to investigate the seminal metabolic signature and whether there are differences in the metabolome between two groups. HSPs were subjected to LC–MS-MS analysis. MetaboAnalyst5.0 software was utilized for statistical analysis. Different univariate and multivariate analyses were used, including T-tests, fold change analysis, random forest (RF), and metabolite set enrichment analysis (MSEA). Teratozoospermic samples contained seventeen significantly different amino acids. Upregulated metabolites include glutamine, asparagine, and glycylproline, whereas downregulated metabolites include cysteine, γ-aminobutyric acid, histidine, hydroxylysine, hydroxyproline, glycine, proline, methionine, ornithine, tryptophan, aspartic acid, argininosuccinic acid, α-aminoadipic acid, and β-aminoisobutyric acid. RF algorithm defined a set of 15 metabolites that constitute the significant features of teratozoospermia. In particular, increased glutamine, asparagine, and decreased cysteine, tryptophan, glycine, and valine were strong predictors of teratozoospemia. The most affected metabolic pathways in teratozoospermic men are the aminoacyl-tRNA, arginine, valine-leucine, and isoleucine biosynthesis. Altered metabolites detected in teratozoospermia were responsible for various roles in sperm functions that classified into four subgroups as follows: related metabolites to antioxidant function, energy production, sperm function, and spermatogenesis. The altered amino acid metabolome identified in this study may be related to the etiology of teratozoospermia, and may provide novel insight into potential biomarkers of male infertility for therapeutic targets.

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Data Availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Funding

The research leading to these results received funding from Avicenna Research Institute under Grant Agreement No 970412–057.

Author information

Author notes

  1. Elham Hosseini and Naser Amirjannati contributed equally to this work as are considered co-first authors.

Authors and Affiliations

  1. Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

    Elham Hosseini

  2. Department of Obstetrics and Gynecology, Mousavi Hospital, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Elham Hosseini

  3. Department of Andrology and Embryology, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Naser Amirjannati

  4. Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK

    Ralf Henkel

  5. Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa

    Ralf Henkel

  6. LogixX Pharma, Theale, Berkshire, UK

    Ralf Henkel

  7. Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Mahshid Bazrafkan

  8. Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Hanieh Moghadasfar & Kambiz Gilany

  9. Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran

    Kambiz Gilany

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  1. Elham Hosseini
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Contributions

E.H contributed to the analysis and interpretation of data, and drafted the manuscript; N.A.J participated in the design of the study and patient recruitment; R.H and M.B contributed to the analysis and interpretation of data; R.H was involved in the revising manuscript critically for data interpretation. H.M contributed to the data acquisition. K.G participated in the design of the study, interpretation of data, and drafting of the manuscript; all authors were involved in revising the manuscript critically for data interpretation, and final approval of manuscript.

Corresponding author

Correspondence to Kambiz Gilany.

Ethics declarations

The study was approved by the Ethics Committee of Islamic Azad Tehran Medical Sciences University-Pharmacy and Pharmaceutical Branches Faculty (NO, IR.IAU.PS.REC.1398.041).

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Informed consent was obtained from all individual participants included in the study.

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Hosseini, E., Amirjannati, N., Henkel, R. et al. Targeted Amino Acids Profiling of Human Seminal Plasma from Teratozoospermia Patients Using LC–MS/MS. Reprod. Sci. 30, 3285–3295 (2023). https://doi.org/10.1007/s43032-023-01272-2

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