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Cellular Signaling by Fibroblast Growth Factors (FGFs) and Their Receptors (FGFRs) in Male Reproduction

Department of Cell Biology (L.M.C., B.T.H.), University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; and Monash Institute of Medical Research (M.K.O.) and The Australian Research Council Centre of Excellence in Biotechnology and Development (M.K.O.), Monash University, Melbourne 3168, Australia

Correspondence: Address all correspondence and requests for reprints to: Barry T. Hinton, Ph.D., Department of Cell Biology, University of Virginia Health Sciences Center, P.O. Box 800732, Charlottesville, Virginia 22908. E-mail: bth7c{at}virginia.edu

The major function of the reproductive system is to ensure the survival of the species by passing on hereditary traits from one generation to the next. This is accomplished through the production of gametes and the generation of hormones that function in the maturation and regulation of the reproductive system. It is well established that normal development and function of the male reproductive system is mediated by endocrine and paracrine signaling pathways. Fibroblast growth factors (FGFs), their receptors (FGFRs), and signaling cascades have been implicated in a diverse range of cellular processes including: proliferation, apoptosis, cell survival, chemotaxis, cell adhesion, motility, and differentiation. The maintenance and regulation of correct FGF signaling is evident from human and mouse genetic studies which demonstrate that mutations leading to disruption of FGF signaling cause a variety of developmental disorders including dominant skeletal diseases, infertility, and cancer. Over the course of this review, we will provide evidence for differential expression of FGFs/FGFRs in the testis, male germ cells, the epididymis, the seminal vesicle, and the prostate. We will show that this signaling cascade has an important role in sperm development and maturation. Furthermore, we will demonstrate that FGF/FGFR signaling is essential for normal epididymal function and prostate development. To this end, we will provide evidence for the involvement of the FGF signaling system in the regulation and maintenance of the male reproductive system.

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