O-147 Differential seminal metabolomic signature is related to sperm quality
Authors: Molina N M , Sola-Leyva A , Pérez-Prieto I , Vargas E , Molina M , Yoldi A , Vaquero A , Navas P , Clavero-Gilabert A , Gonzalvo-López M C , Morales N , Ramírez J P , Castilla J A , Aguilera C M , Altmäe S 
Published: August 2021

Abstract

Study question
What is the entire metabolomic profile of human semen and does the metabolic composition differ between men with good-quality and low-quality semen?

Summary answer
Human semen contains ∼700 different metabolites, and the metabolomic signature differs between normozoospermic men and men with altered seminal parameters.

What is known already
Semen contains a wide diversity of metabolites as has been identified in single and targeted metabolite studies. The full composition of metabolites in human semen, however, is not known. The knowledge of the complete metabolic signature in semen and whether there are differences between metabolic composition and seminal quality could enhance our knowledge of possible factors involved in reduced sperm quality and male infertility.

Study design, size, duration
Case-control study, where a total of 100 men (age= 29.73±8.9 years) from March 2019 to March 2020 participated. The study was approved by the Ethics Committee of Investigación Biomédica de Andalucia.

Participants/materials, setting, methods
Semen samples from 69 normozoospermic and 31 oligozoospermic men were collected at the University Hospital and sperm biobank (Ceifer Biobank - NextClinics). The complete metabolome from unprocessed seminal samples was analysed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Raw data were extracted, peak-identified and quality control processed using Metabolon’s hardware and software (metabolon.com). Multiple regression models controlling for age and sample collection centres were applied using R software.

Main results and the role of chance
In total, 695 different metabolites were detected in the seminal samples, where docosahexaenoate (DHA; 22:6n3, PubChem ID 445580), choline phosphate (1014), dihomo-linolenate (20:3n3 or n6, 5280581), docosapentaenoate (n6 DPA; 22:5n6, 6441454), adenosine 3’,5’-cyclic monophosphate (cAMP, 6076) and N-acetylalliin (122164824) metabolites were the most prevalent. The seminal metabolomic profiles differed significantly between men with normal and low sperm parameters. The most abundant metabolites in normozoospermic men belonged to Lipid Super-Pathway, while Nucleotide Super-Pathway was predominant in semen samples with low quality (p &lt; 0.05). More specifically, the leading Sub-Pathway in normozoospermic men was Long Chain Polyunsaturated Fatty Acid (n3 and n6), whereas Purine and Pyrimidine Metabolism Sub-Pathway prevailed in low-quality semen samples, where DHA and cAMP dominated in men with normal and low seminal quality parameters, respectively (p &lt; 0.05 in all comparisons).

Limitations, reasons for caution
This is the first study presenting the entire metabolome signature of unprocessed human semen, and these preliminary results need to be confirmed in a bigger sample size.

Wider implications of the findings
Semen analyses applied in clinics do not evaluate the functional status of sperm, leaving the infertility causes due to male factor frequently unknown. Our study results could help to understand the molecular background of reduced seminal quality and male infertility and lead to identification of molecular biomarkers of functional sperm.

Trial registration number
not applicable