Researchers at the University of the Basque Country have introduced a new technique for extracting sperm biomarkers from men with low sperm counts, a development that could reshape how male infertility is diagnosed.
New method overcomes long‑standing technical hurdles
The study, published in Cells in April, describes a sonication‑based protocol that gently disrupts sperm cells without destroying the proteins, lipids and sugars needed for detailed analysis.
Traditional approaches rely on harsh detergents that preserve DNA but degrade other biomolecules, limiting insight into the cellular processes that drive fertility.
By applying ultrasonic pulses for 20 seconds at 75% intensity, the team demonstrated that as few as 1.25 million sperm per millilitre can be processed reliably.
This threshold is far below the 200 million per millilitre typical of healthy donors, making the method viable for samples from men facing infertility.
Following cell disruption, the researchers employed high‑performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry to profile the molecular composition of the sperm.
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Using HPLC‑ESI‑MS/MS researchers managed to identify 473 distinct lipid varieties present in human sperm.
Potential impact on diagnosis and treatment
Current fertility assessments rely on WHO guidelines that measure semen volume, sperm concentration, motility and morphology.
PhD student Irune Calzado, lead author of the paper, stated that a semen analysis lacks diagnostic and prognostic capabilities.
Having normal values does not mean that a person is fertile.
The ability to catalogue lipid and metabolite signatures opens the door to discovering biomarkers that differentiate healthy from compromised sperm.
In future work, the researchers aim to compare these profiles across various infertility disorders, seeking patterns that could inform personalized treatment strategies.
Clinicians could eventually use such biomarkers to pinpoint specific metabolic deficiencies, allowing targeted interventions rather than generic recommendations.
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For men undergoing fertility evaluation, the prospect of more precise diagnostics may reduce the uncertainty that often accompanies a “normal” semen analysis but persistent infertility.
If a clear metabolic fingerprint is linked to a particular condition, patients might receive tailored lifestyle or pharmacologic advice, potentially improving their chances of conception.
The study establishes a reproducible workflow that can be applied to larger patient cohorts.
The authors emphasize that the next phase involves mapping alterations in lipid and protein levels across different infertility diagnoses.
Calzado noted that the team will need to explore what happens to these metabolites in each disorder.
All of that remains to be explored.
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