Using publicly available transcriptomic data to identify mechanistic and diagnostic biomarkers in azoospermia and overall male infertility

Temidayo S. Omolaoye,Mahmood Yaseen Hachim,Stefan S. du Plessis

doi:10.1038/s41598-022-06476-1

Temidayo S. Omolaoye, Mahmood Yaseen Hachim + Show 1 more

Open Access

https://doi.org/10.1038/s41598-022-06476-1

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Abstract

Azoospermia, which is the absence of spermatozoa in an ejaculate occurring due to defects in sperm production, or the obstruction of the reproductive tract, affects about 1% of all men and is prevalent in up to 10–15% of infertile males. Conventional semen analysis remains the gold standard for diagnosing and treating male infertility; however, advances in molecular biology and bioinformatics now highlight the insufficiency thereof. Hence, the need to widen the scope of investigating the aetiology of male infertility stands pertinent. The current study aimed to identify common differentially expressed genes (DEGs) that might serve as potential biomarkers for non-obstructive azoospermia (NOA) and overall male infertility. DEGs across different datasets of transcriptomic profiling of testis from human patients with different causes of infertility/ impaired spermatogenesis and/or azoospermia were explored using the gene expression omnibus (GEO) database. Following the search using the GEOquery, 30 datasets were available, with 5 meeting the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEO2R tool. The annotated genes of the probes in each dataset were intersected with DEGs from all other datasets. Enriched Ontology Clustering for the identified genes was performed using Metascape to explore the possible connection or interaction between the genes. Twenty-five DEGs were shared between most of the datasets, which might indicate their role in the pathogenesis of male infertility. Of the 25 DEGs, eight genes (THEG, SPATA20, ROPN1L, GSTF1, TSSK1B, CABS1, ADAD1, RIMBP3) are either involved in the overall spermatogenic processes or at specific phases of spermatogenesis. We hypothesize that alteration in the expression of these genes leads to impaired spermatogenesis and, ultimately, male infertility. Thus, these genes can be used as potential biomarkers for the early detection of NOA.

Highlights

The current study used publicly available transcriptomic data to identify DEGs that are of importance in NOA and overall male fertility
Some of which are important in sperm motility, capacitation, and gonadal development, are essential for male fertility
RIMBP3 is involved in manchette formation; for normal sperm morphology, CABS1, ROPN1L and GTSF1 are involved in flagellum development; for normal sperm motility, SPATA20 is involved in acrosome formation, maintains mitochondria function during spermatogenesis, while SPATA and TSSK1B are both important for sperm maturation

Summary

Methods

The gene expression omnibus (GEO) database was used Www.ncbi.nlm.nih.gov/geo/) to explore the common differentially expressed genes (DEGs) across different datasets of transcriptomic profiling of the testes from human patients with different causes of infertility/impaired spermatogenesis and/or azoospermia. For consistency and to decrease technical confounding factors, the following filters/criteria were used (i) datasets containing only human samples were selected, (ii) expression profiling by microarray for healthy controls and disease groups was used, and (iii) datasets having at least three samples per group were chosen. Among the 30 datasets available on infertility, only 5 fulfilled the inclusion criteria. The phenotype of the datasets as described by the studies include:. This study regarded testicular samples collected from OA patients as control since they presented with complete spermatogenesis

Results

Discussion

Conclusion