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.
Highlights
Fibroblast growth factors (FGFs) constitute a family of 17–34 kDa proteins, being FGF2 the best-characterized member of this family [1, 2]
Expression of FGFR1, FGFR2, FGFR3 and FGFR4 messenger RNA (mRNA) was evaluated in human testis by RT-PCR, using MCF7 cells as control
Using primers designed to recognize sequence regions that are common to all splice variants of each FGFs bind to specific receptors (FGFRs) and commercial antibodies directed against regions conserved in most isoforms, we were able to detect the expression of FGFR1, 2, 3 and 4 mRNA and protein forms in the human testis
Summary
Fibroblast growth factors (FGFs) constitute a family of 17–34 kDa proteins, being FGF2 the best-characterized member of this family [1, 2]. FGFs bind to specific receptors (FGFRs) composed of 3 extracellular immunoglobulin-like domains, a single transmembrane domain, and 2 highly conserved cytoplasmic domains with tyrosine kinase activity. Among FGFRs, the most studied are FGFR1, FGFR2, FGFR3 and FGFR4 [3, 4]. FGFR Expression and Function in Human Sperm manuscript. The specific roles of the authors are articulated in the ‘author contributions’ section
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
