• PMID: 16352663
• Gene Name: FGFR1
• Condition: Associated with normal speramtogenesis
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Associated with normal speramtogenesis

FGFR-1 [corrected] signaling is involved in spermiogenesis and sperm capacitation

Cotton L, Gibbs GM, Sanchez-Partida LG, Morrison JR, de Kretser DM, O'Bryan MK.

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. FAU - Cotton, Leanne AU - Cotton L AD - Monash Institute of Medical Research, Monash University, Melbourne, Australia. FAU - Gibbs, Gerard M AU - Gibbs GM FAU - Sanchez-Partida, L Gabriel AU - Sanchez-Partida LG FAU - Morrison, John R AU - Morrison JR FAU - de Kretser, David M AU - de Kretser DM