Integrative Bioinformatics Analysis of The Cell Division Cycle and Ribosomal Pathways in The Rat Varicocele: Implications for Drug Discovery

Ali Nasr-Esfahani; Ali Valipour Motlagh; Minoo Adib; Kosar Pashaei; Mohammad Hossein Nasr-Esfahani

doi:10.22074/cellj.2023.2004771.1329

Integrative Bioinformatics Analysis of The Cell Division Cycle and Ribosomal Pathways in The Rat Varicocele: Implications for Drug Discovery

Cell J. 2023 Oct 9;25(10):727-737. doi: 10.22074/cellj.2023.2004771.1329.

Authors

Ali Nasr-Esfahani¹, Ali Valipour Motlagh², Minoo Adib³, Kosar Pashaei¹, Mohammad Hossein Nasr-Esfahani⁴

Affiliations

¹ Isfahan Fertility and Infertility Center, Isfahan, Iran.
² Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
³ Department of Immunology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.
⁴ Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Email: mh.nasr-esfahani@royaninstitute.org.

Abstract

Objective: Varicocele is a common cause of male infertility, affecting a substantial proportion of infertile men. Recent studies have employed transcriptomic analysis to identify candidate genes that may be implicated in the pathogenesis of this condition. Accordingly, this study sought to leverage rat gene expression profiling, along with protein-protein interaction networks, to identify key regulatory genes, related pathways, and potentially effective drugs for the treatment of varicocele.

Materials and methods: In this in-silico study, differentially expressed genes (DEGs) from the testicular tissue of 3 rats were screened using the edgeR package in R software and the results were compared to 3 rats in the control group. Data was obtained from GSE139447. Setting a -1<LogFC>1 and P<0.05 as cutoff points for statistical significance, up and down-regulated genes were identified. Based on Cytoscape plugins, protein-protein interaction (PPI) networks were drawn, and hub genes were highlighted. ShinyGO was used for pathway enrichment. Finally, effective drugs were identified from the drug database.

Results: Among the 1277 DEGs in this study, 677 genes were up-regulated while 600 genes were down-regulated in rats with varicocele compared to the control group. Using protein-protein interaction networks, we identified the top five up-regulated genes and the top five down-regulated genes. Enrichment analysis showed that the up-regulated genes were associated with the cell division cycle pathway, while the down-regulated genes were linked to the ribosome pathway. Notably, our findings suggested that dexamethasone may be a promising therapeutic option for individuals with varicocele.

Conclusion: The current investigation indicates that in varicocele the cell division cycle pathway is up-regulated while the ribosome pathway is down-regulated compared to controls. Based on these findings, dexamethasone could be considered a future candidate drug for the treatment of individuals with varicocele.

Keywords: Cell Division Cycle; RNA-Seq; Varicocele.