Fibroblast Growth Factor Receptors (FGFRs) in Human Sperm: Expression, Functionality and Involvement in Motility Regulation

PLoS One. 2015 May 13;10(5):e0127297. doi: 10.1371/journal.pone.0127297. eCollection 2015.

Abstract

Fibroblast growth factors receptors (FGFRs) have been widely characterized in somatic cells, but there is scarce evidence of their expression and function in mammalian gametes. The objective of the present study was to evaluate the expression of FGFRs in human male germ cells, to determine sperm FGFR activation by the FGF2 ligand and their participation in the regulation of sperm motility. The expression of FGFR1, 2, 3 and 4 mRNAs and proteins in human testis and localization of these receptors in germ cells of the seminiferous epithelium was demonstrated. In ejaculated sperm, FGFRs were localized to the acrosomal region and flagellum. Sperm exposure to FGF2 caused an increase in flagellar FGFR phosphorylation and activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB or Akt) signaling pathways. Incubation with FGF2 led to a significant increase in the percentage of total and progressive sperm motility, as well as in sperm kinematics. All responses were prevented by sperm preincubation with BGJ398, a specific inhibitor of FGFR tyrosine kinase activity. In addition to confirming the expression of FGFRs in germ cells of the human testis, our study describes for the first time the presence, localization and functionality of human sperm FGFRs, and provides evidence of the beneficial effect of FGF2 upon sperm motility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fibroblast Growth Factor 2 / physiology
  • Gene Expression
  • Humans
  • MCF-7 Cells
  • Male
  • Protein Transport
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Seminiferous Tubules / cytology
  • Seminiferous Tubules / metabolism
  • Signal Transduction
  • Sperm Motility*
  • Spermatozoa / physiology*

Substances

  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 2

Grants and funding

This study was supported by the Fundación Florencio Fiorini and the National Agency to Promote Science and Technology (ANPCyT; PICT 2013 # 627) to CMB, as well as the National Research Council of Argentina (CONICET) (grant PIP 2008 2120 to MHVL and 2012 740 to MHVL and CMB). Reprolab provided support in the form of salaries for author MJM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the authors are articulated in the ‘author contributions’ section.