In Silico Analysis of CatSper Family Genes and APOB Gene Regulation in Male Infertility

Adv Exp Med Biol. 2022:1391:323-332. doi: 10.1007/978-3-031-12966-7_18.

Abstract

Sperm concentration and sperm motility are the two major causes of male infertility. Having spermatozoa in semen without motility or flagellum tail defect is a major concern needed to be investigated. The CatSper genes are the novel family of four sperm-specific Ca2+-permeable channels which plays an important role in sperm motility, acrosome reaction, sperm, and oocyte fusion. CatSper1, CatSper2, and CatSper3 are very well-studied genes for their role in asthenozoospermia, but the association of these genes with metabolic genes is still unstudied. Another unrevealed aspect is how ROS alter the function of CatSper genes. Among the Catsper family genes, the role of CatSper4 gene must be explored more. In this study, we have used the in silico approach to find the connection between the CatSper family gene with glycolytic genes and also the involvement of CATSPER4 protein in sperm flagellum using the STRING database. Connection of CATSPER1 protein with lipid metabolic gene is also found in Reactome database, and after that gene ontology of these genes was done by using DAVID and Enrichr databases. This analysis showed a strong interaction between CATSPER1, CATSPER2, and CATSPER3 protein with glycolytic protein (i.e., GAPDHS and PGK2), and CATSPER4 protein shows strong relation in the function of sperm flagellum. We also found a novel gene, i.e., APOB contributing to sperm motility. Gene ontology showed the role of APOB and glycolytic proteins in sperm motility. Enrichr analysis showed the association of APOB and glycolytic proteins in asthenozoospermia and CATSPER4 protein with sperm flagellum. Elsevier Pathway Collection also showed proteins involved in male infertility (i.e., GAPDHS). Therefore, we report the role of the CatSper4 gene in sperm tail function and the APOB novel gene involved in sperm motility. Understanding the molecular mechanism(s) of regulations of the CatSper family gene will help us to develop new therapeutic approaches in infertile males.

Keywords: Asthenozoospermia; CatSper genes; Glycolytic genes; Lipid metabolic genes; Male infertility; Sperm flagellum; Sperm motility.

MeSH terms

  • Humans
  • Infertility, Male* / genetics
  • Ion Channels
  • Male
  • Multigene Family*
  • Semen
  • Sperm Motility / genetics

Substances

  • CATSPER3 protein, human
  • Ion Channels
  • APOB protein, human