Dysregulated Kinase Expression in Teratozoospermia and Implications  for Male Infertility: An Integrated Gene Expression Study

Seyedeh Zahra  Mousavi; Morteza  Hadizadeh; Bahram Mohammad  Soltani; Mehdi  Totonchi

doi:10.18502/jri.v26i4.21088

Seyedeh Zahra Mousavi Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Morteza Hadizadeh Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
Bahram Mohammad Soltani Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Mehdi Totonchi Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

DOI: https://doi.org/10.18502/jri.v26i4.21088

Keywords: Gene expression, Microarray analysis, Phosphotransferases, Teratozoospermia.

Abstract

Background: Teratozoospermia, characterized by abnormal sperm morphology, is a major contributor to male infertility. Kinases, enzymes that catalyze the transfer of phosphate groups to proteins, are crucial regulators of cellular signaling pathways and play significant roles in sperm development and maturation. The purpose of the current study was to identify differentially expressed genes (DEGs) between teratozoospermia and normozoospermia samples and to investigate the role of kinases in these expression changes.

Methods: An integrated analysis of transcriptome data was conducted from teratozoospermia and normozoospermia samples using publicly available gene expression omnibus (GEO) datasets. Three gene expression series (GSE) profiles of teratozoospermia from one superseries were selected and combined. Differential expression analysis was performed using the limma package in R, applying linear modeling and empirical Bayes statistics to identify DEGs with a threshold of adjusted p<0.05. A comprehensive list of human kinase genes was obtained from the KinHub database, and differentially expressed kinases between the two conditions were identified. Functional enrichment analyses including gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathways were conducted. Additionally, receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic potential of identified kinases.

Results: Our analysis identified 1,292 DEGs. Among these, 34 kinases were identified (10 upregulated and 24 downregulated). ROR1 and STK39 showed the most significant changes. ROC analysis demonstrated strong diagnostic values for these kinases.

Conclusion: This study is the first comprehensive analysis integrating transcrip-tomic data and kinase-focused gene expression profiling specifically in teratozo-ospermia, suggesting that kinase dysregulation may contribute to teratozoospermia and male infertility.