5
ESSM
Today
Scientific Highlights from Istanbul:
Preclinical Research
by Maarten Albersen
Maarten albersen, Md, Phd
Laboratory of Experimental Urology,
Department of Development
and Regeneration
University of Leuven, Belgium
Translational and basic science provides new
insights in the pathophysiology of sexual disor-
ders and is aimed at identifying new treatment
targets that may provide hope for the future
treatment of a variety of sexual dysfunctions.
As such, the basic and translational science
section provides delegates of the conference
not only with a deeper and broader insight in
the mechanisms underlying the diseases they
treat day-by-day, but also gives an outlook onto
the future of our practice.
This year in Istanbul, the first round table session
encompasses basic research geared towards
elucidating the pathophysiology of premature
ejaculation, but on the other hand is combined
with clinical practice advise. So the delegates
get a broad overview of this disorder from bed-
to-bedside. In RT-07, an overview is given of
pathophysiological aspects of development of
erectile dysfunction in aging, diabetes, cavern-
ous nerve injury and patients with vascular risk
factors and oxidative stress, while Prof. Giuliano
will update us on the role of the spinal cord
in sexual disorders in EFS gold medal session
GM-03. Two master lectures, ML-07 and ML-08
will deal with basic and translational hot top-
ics being sexual desire in animal models and
regenerative medicine. If we take a look into
basic & translational science abstracts, we can
say that we had a strong round of submissions
this year, which is reflected by the high quality
of abstracts in the podium and poster sessions
covering preclinical science. As noted last year,
a clear imbalance between male (MSD) and fe-
male (FSD) sexual dysfunction abstracts in basic
research is apparent, with FSD research clearly
being underrepresented. While not necessarily
representing a lack of interest by researchers,
this finding parallels the difficulties research-
ers are experiencing in seeking support for FSD
preclinical research.
At this note, I would like to initiate the abstract
highlights with two FSD basic research ab-
stracts that have investigated determinants
of NO signaling in the female genital organs.
Ückert et al. (PS-01-015) have looked into the
distribution of TRPA1 channels in the human
clitoris and vagina and found that this ion chan-
nel might be involved in afferent transmission
in female genital organs and work synergisti-
cally together with the NO/cyclic GMP pathway.
Vignozzi et al. (PS-01-016) have worked on
the NO-cGMP pathway in the rat clitoris and
found that that testosterone improves the NO-
mediated signaling, whilst estradiol stimulates
the contractile RhoA/ROCK signaling in clitoris,
thus confirming a positive role of testosterone
in female genital arousal.
A topic that keeps driving basic and translational
researchers is metabolic syndrome and its ef-
fects on erectile function. Various determinants
of metabolic syndrome are discussed this year
including diabetes, hypercholesterolemia, but
also a direct interaction of insulin with NO-
signaling in the corpus cavernosum smooth
muscle. In PS-01-005, Filippi et al. studied the
role of steatohepatitis as a new player in meta-
bolic syndrome-associated erectile dysfunction
in rabbits on a high-fat diet. They performed a
mRNA expression analysis of genes related to
steatohepatitis and found that genes related to
inflammation (TNFalpha, various interleukins and
chemokines, COX-2), immune-response (CD68 –
a macrophage marker, TLR2, TLR4, GATA3),
activation of stellate cells (RhoA, TGFbeta, al-
phaSMA, ETA, ETB), fibrosis (matrix proteases),
and lipid metabolism were negatively associ-
ated to penile maximal responsiveness to ace-
tylcholine in in vitro contractility studies. When
all these putative liver determinants of penile
relaxant capacity to acetylcholine were intro-
duced as covariates in a multivariate model, only
TNFalpha was an important determinant, and
circulating levels of TNFalpha were increased
by a factor of five in high fat diet rabbits as
compared to controls (p<0.02). In my personal
view this is a very well conducted study that is
definitely one of the basic science highlights of
this conference. The same group investigated the
effects of metformin on adenosine signaling in
the penis of high fat diet animals (PS-01-006).
Metformin treatment reduces gluconeogenesis
and was used to chronically treat high fat fed
animals. Metformin treatment normalized the
decreased expression of various adenosine
receptors and increased relaxant responses to
adenosine in-vitro.
In PS-01-008 Martinez-Salamanca and col-
leagues further investigated the link between
diabetes and erectile dysfunction. In addition
to regulate glucose homeostasis, insulin has
been demonstrated to influence vascular func-
tion at local level. The aim of their work was
to characterize the effects of insulin in human
corpus cavernosum and penile resistance ar-
teries and analyzing its interactions with NO/
cGMP pathway. They conclude that insulin
causes human penile smooth muscle relaxa-
tions that are mediated by NO/cGMP pathway,
contributed by endothelium, and impaired by
the presence of ED. Altered regulation of penile
smooth muscle tone by insulin could contribute
to ED in metabolic disorders. Costa et al. inves-
tigated circulating endothelial progenitor cells
(EPCs) in ED (HP-01-007). Results revealed
that in the diabetic bone marrow there was a
reduced production of (CXCR4+) EPCs, when
compared to controls. Regarding peripheral
mobilized cells, the authors observed a more
pronounced decreased in the overall CXCR4+
population in diabetic animals. Additionally,
a decrease in SDF-1a protein expression in
diabetic erectile tissue was detected. Since
SDF-1 is a chemokine that attracts CXCR4-
expressing cells, the authors came to the con-
clusion that effective recruitment of endothelial
progenitor cells to diabetic erectile tissue may
be impaired.
