8 / 330
8
28
TH
CONGRESS OF THE ESPU
13:39–13:42
S1-4 (PP)
THE ROLE OF FGFS IN THE EARLY DEVELOPMENT
OF THE URETHRA: RARE INSIGHTS FROM HUMAN FETAL
SPECIMENS
Felix NÄGELE
1
, Bernhard HAID
2
, Jozsef DUDAS
3
, Alexander HAIM
4
,
Michael BLUMER
1
, Josef OSWALD
5
and Elisabeth PECHRIGGL
1
1) Medical University Innsbruck, Clinical and Functional Anatomy, Innsbruck, AUSTRIA - 2) Hospital of the Sisters
of Charity, Department of Pedatric Urology, Innsbruck, AUSTRIA - 3) Medical University Innsbruck, Department
of Otolaryngology, Innsbruck, AUSTRIA - 4) Medical University Innsbruck, Department of Plastic, Reconstructive
and Aesthetic Surgery, Innsbruck, AUSTRIA - 5) Hospital of the Sisters of Charity, Department of Plastic, Reconstructive
and Aesthetic Surgery, Linz, AUSTRIA
PURPOSE
Fibroblast growth factors (FGFs), especially FGF8 and FGF10, are required for the development of
the anlagen of the external genitalia and also act as regulatory components in the urethral forma-
tion. Lack of these molecules or their associated receptor FGFR2, as shown in murine knock-out
models, leads to congenital malformations of the external genitalia and in particular to hypospadias.
Currently, there are no studies describing the localization and distribution of FGF8/10/R2 in human
fetal specimens.
MATERIAL AND METHODS
25 human fetal specimens, representing an uninterrupted series of 5 specimens for each gestational
week 8-12 were studied. The distribution of FGF8/10/R2 was assessed by means of standardized
immunohistochemistry (Ventana
®
, Roche) using specific anti-FGF8/10/R2 antibodies. The future
urethra could be definitely identified in all specimens, resulting in meaningful readouts.
RESULTS
FGF 8 and FGF10 were consistently present in both the epithelium of the urogenital sinus, in
the urethral plate and in the surrounding mesenchyme, especially in the anlage of the corpora
spongiosa in all specimens. Conversely, FGFR2 occurred in the urethral epithelium and showed
accentuated staining at the contact site between urogenital sinus and mesonephric duct pointing at
its particular role as promotor of the mesothelial-epithelial interaction.
CONCLUSIONS
The findings from murine models could be replicated in our human fetal series. A well-orchestrated
FGF-signaling in the early human fetal period seems to be crucial in the development of the external
genitalia and the urethra in particular. These findings will be further endorsed by in-situ hybridization
assays.