
TY  - JOUR
A1  - Cotton, L. M. 
A1  - Gibbs, G. M. 
A1  - De Kretser, D. M. 
A1  - O'Bryan, M. K. 
T1  - 257. Fibroblast growth factor receptor-1 (FGFR-1) is essential for spermiogenesis and male fertility
JF  - Reproduction, Fertility and Development
JO  - Reprod. Fertil. Dev.
Y1  - 2004
VL  - 16
IS  - 9
SP  - 257
EP  - 257
KW  - 
UR  - https://doi.org/10.1071/SRB04ABS257 
N2  - SNTs (Suc-1 associated Neurotrophic Factor Targets) are FGF signalling adaptors and crucial activators of the MAP/PI3 kinase pathways via FGFRs. Screening a rat testis library identified snt-2 as a potential ODF component. ODFs are a major constituent of the sperm tail that we hypothesise play an active role in motility. Using western blot analysis I have localised Fgfr-1 to the sperm tail. As such, I propose that Fgf signalling through snt-2 is involved in sperm tail development/function. To test this hypothesis, I created transgenic mice carrying a dominant-negative variant of Fgfr-1 driven by the protamine 1 promoter (haploid specific). Breeding experiments confirmed males were fertile, although one line showed a tendency towards reduced pup numbers. This effect was strengthened by Daily Sperm Production (DSP), showing significantly reduced DSP (30%&#8595;) compared to wt mice. Transgene expression levels were expressed up to 70 times above native mRNA levels in wt mice&#x003B; however there was a concurrent up-regulation of the native receptor in transgenic mice. Cumulatively this resulted in only a 6x over-expression in transgene: native mRNA, and illustrated the presence of a feedback mechanism controlling Fgfr-1 expression. To increase transgene expression, I crossed independent lines (double heterozygous, DH) males. Breeding experiments showed males from 1 cross were significantly subfertile (2 v. 10 in wt mice) . DSPs were further reduced, (41%&#8595;) compared to wt mice. Collectively this data shows Fgfr-1 signalling is required for quantitatively normal spermiogenesis, but is also likely to have a post testicular role in sperm function. I hypothesise this is mediated via activation/regulation of motility through the MAP/PI3 kinase pathways. Further, these mouse models provide compelling evidence that infertility in Kallmann&#39;s Syndrome patients is composed of both hypothalamic and testicular components. These mice will provide valuable insights into the signal transduction mechanisms controlling sperm function and avenues for contraceptive development. 
ER  -

