Fibroblast Growth Factor Receptors (FGFRs) in human sperm: expression, functionality and involvement in motility regulation

SAUCEDO L; BUFFA GN; ROSSO M; GUILLARDOY T; GONGORA A; MUNUCE, MARÍA JOSÉ ; VAZQUEZ LEVIN, MH; MARIN BRIGGILER CI

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2015 vol. 10

1932-6203

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