Seminal Microbiota of Idiopathic Infertile Patients and Its Relationship With Sperm DNA Integrity

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Abstract
The development of new biomarkers for human male infertility is crucial to improve the diagnosis and the prognosis of this disease. Recently, seminal microbiota was shown to be related to sperm quality parameters, suggesting an effect in human fertility and postulating it as a biomarker candidate. However, its relationship to sperm DNA integrity has not been studied yet. The aim of the present study is to characterize the seminal microbiota of a western Mediterranean population and to evaluate its relationship to sperm chromatin integrity parameters, and oxidative stress. For that purpose, 14 samples from sperm donors and 42 samples from infertile idiopathic patients were obtained and were analyzed to assess the composition of the microbiota through full-length16S rRNAgene sequencing (Illumina MiSeq platform). Microbial diversity and relative abundances were compared to classic sperm quality parameters (macroscopic semen parameters, motility, morphology and concentration), chromatin integrity (global DNA damage, double-stranded DNA breaks and DNA protamination status) and oxidative stress levels (oxidation-reduction potential). The seminal microbiota observed of these samples belonged to the phylaFirmicutes,Proteobacteria,ActinobacteriaandBacteroidetes. The most abundant genera wereFinegoldia,Peptoniphilus,Anaerococcus,Campylobacter,Streptococcus,Staphylococcus,Moraxella,Prevotella,Ezakiella,CorynebacteriumandLactobacillus. To our knowledge, this is the first detection ofEzakiellagenus in seminal samples. Two clusters of microbial profiles were built based on a clustering analysis, and specific genera were found with different frequencies in relation to seminal quality defects. The abundances of several bacteria negatively correlate with the sperm global DNA fragmentation, most notablyMoraxella,BrevundimonasandFlavobacterium. The latter two were also associated with higher sperm motility andBrevundimonasadditionally with lower oxidative-reduction potential.Actinomycetaceae,RalstoniaandPaenibacilluscorrelated with reduced chromatin protamination status and increased double-stranded DNA fragmentation. These effects on DNA integrity coincide in many cases with the metabolism or enzymatic activities of these genera. Significant differences between fertile and infertile men were found in the relative presence of thePropionibacteriaceaefamily and theCutibacterium,RhodopseudomonasandOligotrophagenera, which supports its possible involvement in male fertility. Our findings sustain the hypothesis that the seminal microbiome has an effect on male fertility.
Funding Information
  • Instituto de Salud Carlos III (PI14/00119)
  • Generalitat de Catalunya (2017SGR1796)

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