Insight into the complexity of male infertility: a multi-omics review

Abstract

Male infertility is a reproductive disorder, accounting for 40–50% of infertility. Currently, in about 70% of infertile men, the cause remains unknown. With the introduction of novel omics and advancement in high-throughput technology, potential biomarkers are emerging. The main purpose of our work was to overview different aspects of omics approaches in association with idiopathic male infertility and highlight potential genes, transcripts, non-coding RNA, proteins, and metabolites worth further exploring. Using the Gene Ontology (GO) analysis, we aimed to compare enriched GO terms from each omics approach and determine their overlapping. A PubMed database screening for the literature published between February 2014 and June 2022 was performed using the keywords: male infertility in association with different omics approaches: genomics, epigenomics, transcriptomics, ncRNAomics, proteomics, and metabolomics. A GO enrichment analysis was performed using the Enrichr tool. We retrieved 281 global studies: 171 genomics (DNA level), 21 epigenomics (19 of methylation and two histone residue modifications), 15 transcriptomics, 31 non-coding RNA, 29 proteomics, two protein posttranslational modification, and 19 metabolomics studies. Gene ontology comparison showed that different omics approaches lead to the identification of different molecular factors and that the corresponding GO terms, obtained from different omics approaches, do not overlap to a larger extent. With the integration of novel omics levels into the research of idiopathic causes of male infertility, using multi-omic systems biology approaches, we will be closer to finding the potential biomarkers and consequently becoming aware of the entire spectrum of male infertility, their cause, prognosis, and potential treatment.

Keywords:

• Genomics
• epigenomics
• transcriptomics
• proteomics
• male infertility

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Performed literature screening, curated and interpreted the data, and performed the enrichment analysis: RP. Provided technical advice for the article organization: AH and MS. Coordinated the study and revised the manuscript: TK and BP. Provided scientific advice from the clinical perspective: BP. All authors approved the final manuscript.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Additional information

Funding

This work was supported by the Slovenian Research and Innovation Agency (https://www.aris-rs.si/sl/): Grant No.: P3-0326, P4-0220 and Junior Researcher Grant (RP).