Screening, identification and interaction analysis of key MicroRNAs and genes in Asthenozoospermia

Abstract

Background: Asthenozoospermia, one of the most common causes of male infertility, is a complicate multifactorial pathological condition that genetic factors are involved in. However, the epigenetic signature and mechanism of asthenozoospermia still remain limited. Our study aimed to confirm the key microRNAs (miRNAs) and genes in asthenozoospermia and demonstrate the underlying epigenetic regulatory mechanisms. Methods: We screened out and pooled previous studies to extracted potential differentially expressed miRNAs (DEMs). GSE22331 and a published profile dataset were integrated to identify differentially expressed genes (DEGs). Pathway and gene ontology analysis were performed using DAVID. A protein-protein network (PPI) was constructed using STRING. The target genes of DEMs were predicted using TargetScan and the miRNA-mRNA network was built. Results: We reported 3 DEMs and 423 DEGs by pooling included dataset and published studies. Pathway analysis showed that these DEGs might participate in signaling pathways regulating pluripotency of stem cells, Wnt signaling pathway and Notch signaling pathway. 25 hub genes were identified, and the most significant gene was BDNF. We screened out the overlapped DEGs between the predicted target genes of 3 DEMs and the 423 DEGs. Finally, a potential miRNA-mRNA regulatory network was constructed. Conclusion: This study firstly pooled several published studies and a GEO dataset to determine the significance of potential miRNAs and genes, such as miR-374b, miR-193a, miR-34b, BDNF, NTRK2, HNRNPD and EFTUD2 in regulating asthenozoospermia and underscore their interactions in the pathophysiological mechanism. Our results provided theoretical basis and new clues for potential therapeutic treatment in asthenozoospermia. Validations in vivo and in vitro are required in future studies.

Using microRNAs as molecular biomarkers for the evaluation of male infertility

“…Another similar study with 39 men having unexplained asthenozoospermia was conducted, and the authors found that the expression level of miR‐888‐3p increased significantly in patients with unexplained asthenozoospermia (Heidary et al, 2019). As shown in Table 3, the expression level of miR‐374b was lower in asthenozoospermic cases than infertile men, making it a potential non‐invasive biomarker to predict asthenozoospermia (Li & Chen, 2021). In a recent article, semen samples were collected from a total of 71 infertile men, and a reduction in the expression of miR‐510‐ 5p was reported in the semen samples of patients with teratozoospermia and asthenozoospermia in comparison with case–control (normozoospermia and teratoasthenozoospermia) (Hasheminiya et al, 2020).…”

Bioinformatics analysis identifies potential hub genes and crucial pathways in the pathogenesis of asthenozoospermia

“…In our study, two asthenozoospermia datasets were selected from the GEO database based on previous literature reports, and these data proved to be reliable[ 13 , 15 ]. Two asthenozoospermia GSE profiles include GSE92578 (GPL20301 Illumina HiSeq 4000 [Homo sapiens]), containing 3 asthenozoospermia sample and 4 normal sample[ 9 ], and GSE22331 (GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array), containing one asthenozoospermia and normal sample[ 12 ].…”

“…Abnormalities at the genomic level, including genes and signaling pathways related to this disease, have increasingly been identified between fertile men and patients with asthenozoospermia [8][9][10][11][12]. The large amount of gene sequencing data available has provided a convenient resource for analyzing the regulation of gene expression in asthenozoospermia using increasingly complex analytical techniques [13]. In the current manuscript, we obtained differentially expressed genes (DEGs) in patients with asthenozoospermia using the GSE92578 and GSE22331 datasets from the Gene Expression Omnibus (GEO) database.…”

Short total sleep duration and poor sleep quality might be associated with asthenozoospermia risk: A case-control study

“…Several studies have indicated that asthenozoospermia is due to energy deficiency and structural abnormalities of sperm ( du Plessis et al, 2015 ; Sironen et al, 2020 ). Numerous reasons may contribute to asthenozoospermia, such as varicocele ( Zhu et al, 2018 ), oxidative stress ( Nowicka-Bauer et al, 2018 ), genetic factors ( Li and Chen, 2021 ), environmental pollutants ( Benoff et al, 2008 ), nutrition ( Moghadam et al, 2020 ), and lifestyle ( Gaur et al, 2010 ).…”