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First published online 13 December 2005
doi: 10.1242/jcs.02704

Journal of Cell Science 119, 75-84 (2006)
Published by The Company of Biologists 2006
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Research Article

FGFR-1 signaling is involved in spermiogenesis and sperm capacitation

Leanne Cotton1, Gerard M. Gibbs1, L. Gabriel Sanchez-Partida1, John R. Morrison1, David M. de Kretser1,2 and Moira K. O'Bryan1,2,*

1 Monash Institute of Medical Research, Monash University, Melbourne, Australia
2 The ARC Centre of Excellence in Biotechnology and Development, Monash University, Melbourne, Australia

* Author for correspondence (e-mail: Moira.obryan{at}med.monash.edu.au)

Accepted 21 September 2005

Cloning of the fibroblast growth factor receptor (FGFR) adaptor Snt-2 cDNA and the identification of FGFR-1 protein in association with sperm tails, suggested that FGFR-1 signaling was involved in either sperm tail development or function. This hypothesis was tested by the creation of transgenic mice that specifically expressed a dominant-negative variant of FGFR-1 in male haploid germ cells. Mating of transgenic mice showed a significant reduction in pups per litter compared with wild-type littermates. Further analysis demonstrated that this subfertility was driven by a combination of reduced daily sperm output and a severely compromised ability of those sperm that were produced to undergo capacitation prior to fertilization. An analysis of key signal transduction proteins indicated that FGFR-1 is functional on wild-type sperm and probably signals via the phosphatidylinositol 3-kinase pathway. FGFR-1 activation also resulted in the downstream suppression of mitogen activated protein kinase signaling. These data demonstrate the FGFR-1 is required for quantitatively and qualitatively normal spermatogenesis and has a key role in the regulation of the global tyrosine phosphorylation events associated with sperm capacitation.

Key words: FGFR-1, Sperm, Capacitation, Fertility, Spermatogenesis




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