Infertility network and hub genes for nonobstructive azoospermia utilizing integrative analysis

Abstract

Non-obstructive azoospermia (NOA) is the most severe form of male infertility owing to the absence of sperm during ejaculation as a result of failed spermatogenesis. The molecular mechanisms of NOA have not been well studied. Here, we revealed the dysregulated differentially expressed genes in NOA and related signaling pathways or biological processes. Cluster features of biological processes include spermatogenesis, fertilization, cilium movement, penetration of zona pellucida, sperm chromatin condensation, and being significantly enriched metabolic pathways in proximal tubule bicarbonate reclamation, aldosterone synthesis and secretion, glycolysis and glycogenesis pathways in NOA using Gene Ontology analysis and pathway enrichment analysis. The NOA gene co-expression network was constructed by weighted gene co-expression network analysis to identify the hub genes ( CHD5 and SPTBN2 ). In addition, we used another Gene Expression Omnibus dataset (GSE45887) to validate these hub genes. Furthermore, we used the Seurat package to classify testicular tissue cells from NOA patients and to characterize the differential expression of hub genes in different cell types from different adult males based on the scRNA-seq dataset (GSE106487). These results provide new insights into the pathogenesis of NOA. Of particular note, CHD5 and SPTBN2 may be potential biomarkers for the diagnosis and treatment of NOA.

Application of single-cell RNA sequencing on human testicular samples: a comprehensive review

“…Meanwhile, the interested genes were not restricted to one gene or several genes, the researchers could detect a gene family (such as Interleukins) or a series of function-related genes (such as inflammatory cytokine receptors) in scRNA-seq data 142 , which could give researchers a view on macroscale. Moreover, an updated usage of this process was to not only show the type of cells that a certain gene was expressed in, but also show its transcriptional changes during spermatogenesis 143 or among different pathological groups 127 , 144 . A good example came from He et al's work 127 , in which they identified four interested genes ( KIF2C , MRPS2 , RPS15 and TSFM ), and then based on human scRNA-seq data of both KS testes and normal testes, they showed that KIF2C were downregulated while RPS15 were upregulated in KS testes.…”

CHD5 gene (rs9434741) might be a genetic risk factor for infertility in non‐obstructive azoospermia and severe oligozoospermia

“…It seems that SNP analysis has also shown a strong association between sperm chromatin structure and infertility, and some genes have the potential to become biomarkers. Han et al in 2021 showed that CHD5 may be a potential biomarker for the diagnosis and treatment of NOA (Han et al, 2021). However, the results of different reports do not match and the reason may be found in semen parameters, racial divisions and other gene interventions.…”

“…genes have the potential to become biomarkers Han et al in 2021. showed that CHD5 may be a potential biomarker for diagnosis and treatment of NOA(Han et al, 2021).…”

Construction and external validation of a 5-gene random forest model to diagnose non-obstructive azoospermia based on the single-cell RNA sequencing of testicular tissue

“…In addition, from the perspective of pathogenesis, although many theories have been proposed to explain the pathogenesis of NOA, our understandings of the biological processes associated with NOA remains insufficient. Nowadays, the widespread applications of gene sequencing, especially scRNA-seq, have deepened the knowledge of NOA [ 25 , 26 ]. For instance, Wang et al had disclosed the unique role of autophagy homeostasis in the spermatogenesis of NOA cases through scRNA-seq analysis [ 27 ].…”