Whole-Genome Profile of Greek Patients with Teratozοοspermia: Identification of Candidate Variants and Genes

Abstract

Male infertility is a global health problem that affects a large number of couples worldwide. It can be categorized into specific subtypes, including teratozoospermia. The present study aimed to identify new variants associated with teratozoospermia in the Greek population and to explore the role of genes on which these were identified. For this reason, whole-genome sequencing (WGS) was performed on normozoospermic and teratozoospermic individuals, and after selecting only variants found in teratozoospermic men, these were further prioritized using a wide range of tools, functional and predictive algorithms, etc. An average of 600,000 variants were identified, and of them, 61 were characterized as high impact and 153 as moderate impact. Many of these are mapped in genes previously associated with male infertility, yet others are related for the first time to teratozoospermia. Furthermore, pathway enrichment analysis and Gene ontology (GO) analyses revealed the important role of the extracellular matrix in teratozoospermia. Therefore, the present study confirms the contribution of genes studied in the past to male infertility and sheds light on new molecular mechanisms by providing a list of variants and candidate genes associated with teratozoospermia in the Greek population.

The Regulatory Effects of JAK2/STAT3 on Spermatogenesis and the Redox Keap1/Nrf2 Axis in an Animal Model of Testicular Ischemia Reperfusion Injury

“…Bioinformatics and in vivo studies confirmed a correlation between the expression of proteins in the JAK pathway with hypoxia and oligozoospermia [ 33 ]. JAK was recently identified in a whole-genome profile as a new variant associated with teratozoospermia, indicating its involvement in male infertility [ 34 ]. However, data from bioinformatic analyses need in vivo research to investigate the exact role of JAK isoforms in spermatogenesis and sperm function.…”

Chromosomal Abnormalities in Infertile Greek Men: A Single Institution’s Experience

“…The advent of high throughput technologies, like Next-Generation Sequencing, and genomewide association studies have led to the discovery of several novel promising candidate genes responsible for male infertility, which after validation, could serve as biomarkers for the development of a gene panel-based diagnostic testing in the future [20]. Recently, the first study performed in teratozoospermic Greek patients using Whole Genome Sequencing confirmed the role of already known genes involved in male infertility and enlisted several candidate genes and variants that are associated with teratozoospermia [21]. Epigenetic changes such as DNA methylation, histone modification and non-coding RNA have also been shown to significantly contribute to male infertility.…”

Male Infertility: From Genes to Genomes 2022

“…Therefore, it is suggested that genome instability may be an independent characteristic of sperm quality, detecting problems that sperm analysis alone does not detect. Kyrgiafini et al (2022) [8] used a whole-genome sequencing approach to analyze the genomes of men diagnosed with teratozoospermia, and through a comparison with the genomes of normozoospermic men they identified several genetic variants and genes that may play a role in the development of this condition. More specifically, after variant prioritization and bioinformatics analysis they detected high-impact variants in approximately sixty genes.…”