249. Fibroblast growth factor receptor-1 (FGFR-1) is essential for spermiogenesis, capacitation and male fertility
L. M. Cotton A , G. M. Gibbs A , D. M. De Kretser A B and M. K. O’Bryan A BA Monash University, Monash Institute of Medical Research, Clayton, VIC, Australia
B ARC Centre of Excellence in Biotechnology and Development, Australia
Reproduction, Fertility and Development 17(9) 99-99 https://doi.org/10.1071/SRB05Abs249
Submitted: 26 July 2005 Accepted: 26 July 2005 Published: 5 September 2005
Abstract
Male infertility is often a result of irregular sperm development/function. The identification of snt-2 (Suc-1 associated Neurotrophic Factor Target 2) and Fgfr-1 to the sperm tail, lead to the hypothesis that Fgf signalling through snt-2 is involved in sperm tail development/function. To test this hypothesis, transgenic mice carrying a dominant-negative variant of Fgfr-1, driven by the protamine 1 promoter (haploid specific) were created. Breeding experiments confirmed male fertility; however, one line was significantly sub-fertile and demonstrated a significantly reduced daily sperm production (DSP, 30%↓). Transgene expression levels were up to 70 times above native mRNA levels in wt mice; however, there was a concurrent upregulation of the native receptor in transgenic mice, resulting in only a 6× over-expression in transgenic : native mRNA. To increase transgene expression, independent lines were crossed (double heterozygous, DH). DH transgene expression levels were up to 120 times above the native mRNA in wild type mice, resulting in a 20× over-expression in transgenic : native mRNA. Breeding experiments showed males from 1 cross were significantly subfertile with DSPs further reduced (41%↓). Collectively this data shows Fgfr-1 signalling is required for quantitatively normal spermiogenesis. Given the millions of sperm that mice produce, a 40%↓ in DSP is unlikely to be responsible for the sub-fertility observed i.e. 2 v. 9 pups/litter. Therefore, a disruption of Fgfr-1 signalling may also induce a post-testicular phenotype. Western blot analysis, using tyrosine phosphorylation as a surrogate marker of sperm capacitation, showed transgenic mice had a significantly attenuated ability to initiate capacitation. As capacitation is an absolute requirement for fertilisation, the absence of capacitating capability is probably the major contributor to the sub-fertility seen in the transgenic mice. This research demonstrates for the first time that the Fgfr-1 signalling cascade is one of several pathways associated with sperm development and function.
