Vol 1. No 2. Spring 2008 - Royan Institute

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Vol. 1, No. 2, Spring 2008
The only vision I have is your sight
The only thing I follow is your light.
Everyone finds his repose in sleep,
Sleep from my eyes has taken flight.
Hafiz-e Shirazi (1310-1388)
جز نقش تو در نظر نيامد ما را
جز كوى تو رهگذر نيامد ما را
خواب ارچه خوش آمد همه را در عهدت
حقا كه به چشم در نيامد ما را
حافظ شيرازي
Research Projects in Royan
Institute:
Projects on Process:
1- Differentiation of stem cells to neural cells and
transplantation to rat model of spinal cord injury
2- The effect of low dose HCG on folliculogenesis of
PCO patients undergoing ART
Finished Projects:
1- Culture and proliferation of human limbal stem
cells
2- Effect of phosphodiesterase on in-vitro maturation
and development of immature mouse oocytes
Ethics Symposium – Winter of 2008
Ethical concerns related to embryo donation were
discussed in an one-day symposium, entitled “Embryo
Donation from an Ethical Point of View”, that was held
at the Royan Institute on 3rd Jan 2008. The aim of
this symposium was to discuss a recently passed law
about permission for embryo donation in Iran and to
consider ethical, moral, legal, religious, psychological,
and social views. The symposium lasted 9 hours
and consisted of three sessions held in six panels: 1)
medical and health; 2) psychological; 3) religious; 4)
legal; 5) social; and 6) moral and ethical.
More than 300 scientists and doctors participated in
the symposium and active discussion and question
and answers were the main part of the symposium.
Medical doctors, clergy leaders, law experts,
socialists and psychologists were participated in all
the discussions and this symposium managed to
a declaration. This declaration was sent to all the
infertility centers, hospitals, Iran’s parliament, religious
research centers and medical faculties faculties. “We
hope that the pitfalls of the Embryo donation law will
be corrected in the future” said the chairman of the
symposium, Seyed Taha Merghati. “We try to discuss
about the problem before they make difficult situation
that we cannot control”. The symposium was closed
by the chairman of the health and medical committee
of Iran’s parliament.
AN AMAZING TRIP
By: ELZA MARIA PRESTES SARTORELLI, PhD in Human
Genetics
I was invited to go to Iran to
present my PhD research
at the Royan Institute
Congress, as a poster, in
2002.
At the Congress, besides
meeting many distinguished
scientists from all over the
world, I had the pleasure
of taking a course on
techniques of assisted
reproduction with Iranian
doctors’ experts. The way
they were developing their
work at The Royan Institute
made me realize that they were using the most top
techniques on human infertility there.
The whole team from The Royan Institute welcomed
us in a very special way, trying to show us a bit from
their culture and their way of living.
After all the splendid time we spent in Teheran, we
had the great opportunity of traveling to Shiraz and
Esfahan, a tour guided by a special member from
Royan Institute.
The chance I had in 2002 was an unexpected
happening and a pleasant surprise in my life.
ELZA MARIA PRESTES SARTORELLI, PhD in Human
Genetics
Department of Cellular Biology, Embryology and Genetics
Center of Biological Sciences
University of Santa Catarina, Brazil
Royan Institute
Reproductive Biomedicine Stem Cell Biology
& Technology Tehran, Iran
P.O.Box: 19395 - 4644
Tel/Fax: (+9821) 22310406
E-mail: info@royaninstitute.org

Royan Articles
Int J Androl. 2007 Oct 30
Varicocelectomy: semen parameters and
protamine deficiency.
Nasr-Esfahani MH, Abasi H, Razavi S, Ashrafi
S, Tavalaee M.
Department of Embryology and Andrology, Royan
Institute, Tehran, Iran.
Different methods have been used to evaluate the
beneficial effect of varicocelectomy; these include
semen parameters and pregnancy rate. Because
of high biological variability of semen parameters,
sperm functional tests have been considered as an
efficient end point in assessment of fertility. Therefore,
the aim of this study was to evaluate the effect of
varicocelectomy on semen parameters and sperm
protamine deficiency in 192 patients. The results
of the present study show that all the three semen
parameters and percentage of sperms with normal
protamine content have improved post-surgery. The
cumulative pregnancy rate was 34.6%. Comparing the
results of the semen parameters and protamine content
between patients whose partner became pregnant to
those who did not benefit from varicocelectomy before
and 6 months after surgery, show that patients may
benefit from varicocelectomy that had higher initial
semen density and better sperm morphology prior
to surgery. Detailed analyses of sperm morphology,
along with aforementioned results reveal that the
factors which account for pregnancy difference are:
(i) improvement in early events of spermatogenesis,
possibly during spermatocytogensis and reduction
division; and (ii) late spermiogenesis events. Thus, it
can be suggested that patients with low initial sperm
count may benefit more from assisted reproductive
techniques or varicocelectomy followed by assisted
reproduction.
Cell Biol Int. 2007 Oct 7
Differential effect of activin on mouse
embryonic stem cell differentiation in insulinsecreting
cells under nestin-positive selection
and spontaneous differentiation protocols.
Jafary H, Larijani B, Farrokhi A, Pirouz M,
Mollamohammadi S, Baharvand H.
Department of Stem Cells, Royan Institute, P.O. Box
19395-4644, Tehran, Iran.
DParallel to the importance of the development of
cell therapies to treat diabetes is the production of
sufficient numbers of pancreatic endocrine cells that
function like primary islets. To increase the efficiency
of endocrine pancreatic-like cell differentiation from
mouse embryonic stem cells (ESCs), we applied
activin-B to nestin-positive selection (protocol 1) and
spontaneous differentiation (protocol 2) in different
groups including: [A] activin-B, or [B] basic fibroblast
growth factor (bFGF), and/or [C] activin-B+bFGF. The
differentiated cells expressed most pancreatic-related
genes. The number of insulin- and C peptide-positive
cells, as well as dithizone-positive clusters in group
A of protocol 1 was higher than in the other groups.
Significant insulin concentrations in protocol 1 were
produced when glucose was added to the medium, in
comparison with protocol 2. Moreover, insulin release
was increased significantly in group A of protocol 1 even
with lower glucose. In conclusion, Addition of activin-B
in a nestin-positive selection protocol increased the
insulin-secreting cells in comparison with the same
protocol with bFGF and/or spontaneous differentiation
in presence of bFGF and/or activin-B alone. However,
improvements of the current method are required to
generate a sufficient source of true beta-cells for the
treatment of diabetes mellitus.
Fertil Steril. 2008 Jan 16
Artificial oocyte activation in severe
teratozoospermia undergoing
intracytoplasmic sperm injection.
Nasr-Esfahani MH, Razavi S, Javdan Z, Tavalaee
M.
Department of Embryology and Andrology, Royan
Institute, Tehran, Iran; Isfahan Fertility and Infertility
Center, Isfahan, Iran.
OBJECTIVE: To evaluate efficiency of Ionomycin on
fertilization and cleavage rates, embryo development,
and pregnancy rate after intracytoplasmic sperm
injection (ICSI) in teratozoospermic patients. DESIGN:
Laboratory study. SETTING: Isfahan fertility and
infertility Center, and Royan institute, Tehran, Iran.
PATIENT(S): Eighty-seven couples with male factor
etiology (severe teratozoospermia) undergoing ICSI.
INTERVENTION(S): Ionomycin for artificial oocyte
activation.
MAIN OUTCOME MEASURE(S): After oocyte
collection, the oocytes were randomly divided into
two groups: control and artificial oocyte activation
(AOA). The injected oocytes in the control group were
cultured in G1. The remaining oocytes were chemically
activated by exposure to 10 muM Ionomycin for 10
minutes. Around 16 to 18 hours after ICSI, fertilization
was assessed by the presence of pronuclei. The
percentage of cleavage and high-quality embryos
were calculated 48 and 72 hours after ICSI. Clinical
pregnancy also was determined based on ultrasound
observation of a fetal heart beat. RESULT(S): There
are significant differences in the mean of fertilization
and cleavage rates 72 hours after ICSI between AOA
and control groups. In patients who had no fertilization
in the control group and all the embryos for transfer
derived from the AOA group, two pregnancies were
recorded. In the patients who had poor fertilization rate
(1%-33%) in the control group (14.30%), there was a
significant increase in mean fertilization rate (58.31%)
because of AOA. The results of the present study also
reveal that the samples had motile sperm, whereas in
the chemically activated group this difference was not
significant. CONCLUSION (S): It can be concluded
that in cases with severe teratozoospermia AOA may
improve fertilization and cleavage rates, which in turn,
affect the implantation and pregnancy rate.
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Science Reference
Somatic cell
EA somatic cell is generally taken to mean any cell
forming the body of an organism.
Somatic cells, by definition, are not germline cells.
In mammals, germline cells are the sperm and ova (also
known as “gametes”) which fuse during fertilization to
produce a cell called a zygote, from which the entire
mammalian embryo develops.
Every other cell type in the mammalian body, apart
from the sperm and ova, the cells from which they are
made (gametocytes) and undifferentiated stem cells,
is a somatic cell; internal organs skin, bones, blood
and connective tissue are all made up of somatic
cells.. For more information about the topic Somatic
cell, read the full article at Wikipedia.org ,
Reference: http://www.sciencedaily.com/articles/s/
somatic_cell.htm
Methods in Human
Embryonic Stem Cell Research
October 15, 2008 - October 18, 2008
Bar Harbor, ME, United States
nations in the world present more of a justification for
the study of history than Iran.”
The arrival of the Iranian peoples begins in the early
first millennium BC, and the establishing of the Median
dynasty (728–550 BC) culminated in the first Iranian
Empire. The Medes are credited with the foundation
of Iran as a nation and empire, and established the
first Iranian empire, the largest of its day until Cyrus
the Great established a unified empire of the Medes
and Persians leading to the Achaemenian Empire
(648–330 BC).
Cyrus the Great created the Cyrus Cylinder, considered to
be the first declaration of human rights. He was the first king
whose name has the suffix "Great" and the first Shah of Iran
to be known by that title. Cyrus also banned slavery in all
of the conquered areas that became the Persian Empire.
Cyrus' seminal ideas greatly influenced later human
civilizations; Cyrus' principles of ruling – advocating "love"
rather than "fear"
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18th World
Congress on Ultrasound in
Obstetrics and Gynecology
August 24, 2008 - August 28, 2008
Chicago, IL, United States
A Short History about
IRAN
Early history and the Median and
Achaemenian Empires (900 BC – 330 BC)
The role of Iran in history is highly significant; hence
the German philosopher Georg Wilhelm Friedrich
Hegel considered the ancient Persians to be “the first
historic people” and stated thus:
“In Persia first arises that light which shines itself
and illuminates what is around...The principle of
development begins with the history of Persia; this
constitutes therefore the beginning of history”. “Few
I am Kourosh (Cyrus), King of the world, great
king, mighty king, king of Babylon, king of the land
of Sumer and Akkad, king of the four quarters, son
of Camboujiyah (Cambyases), great king, king of
Anshân, grandson of Kourosh (Cyrus), great king,
king of Anshân, ...
… Now that I put the crown of kingdom of Iran,
Babylon, and the nations of the four directions on the
head with the help of (Ahura) Mazda, I announce that I
will respect the traditions, customs and religions of the
nations of my empire and never let any of my governors
and subordinates look down on or insult them until I
am alive. From now on, till (Ahura) Mazda grants me
the kingdom favor, I will impose my monarchy on no
nation. Each is free to accept it, and if any one of them
rejects it, I never resolve on war to reign. Until I am
the king of Iran, Babylon, and the nations of the four
directions, I never let anyone oppress any others, and
if it occurs, I will take his or her right back and penalize
the oppressor...
http://en.wikipedia.org/wiki/History_of_Iran
& http://www.iranchamber.com/history/cyrus/cyrus_
charter.php

Science News
Science News
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Blood Stem Cells Originate And Are Nurtured In
The Placenta
ScienceDaily (Mar. 6, 2008)
Solving a long-standing biological mystery, UCLA
stem cell researchers have discovered that blood
stem cells, the cells that later differentiate into all the
cells in the blood supply, originate and are nurtured in
the placenta.
The discovery may allow researchers to mimic the
specific embryonic microenvironment necessary for
development of blood stem cells in cell culture and
grow them for use in treating diseases like leukemia
and aplastic anemia, said Dr. Hanna Mikkola, a
researcher in the Eli and Edythe Broad Center of
Regenerative Medicine and Stem Cell Research and
senior author of the study.
“It was a big mystery, where these cells originated,”
said Mikkola, an assistant professor of molecular,
cell and developmental biology. “This is the first
time we can really say definitively that blood stem
cells are generated in the placenta. There’s no more
speculation.”
The study published March 6, 2008 in the journal Cell
Stem Cell. Researchers in Mikkola’s lab are working
now to replicate this work, done in mouse models, in
humans.
If researchers could grow blood stem cells, those cells
could be transplanted into these patients. The blood
stem cells would then differentiate into a new, and
healthy, blood supply. And with the recent success
in creating induced pluripotent stem cells (iPS) from
human skin cells, a patient’s own skin cells could
perhaps be used to create iPS cells. Those cells could
then be transformed into blood stem cells, creating
an immune-compatible source of blood supply that
eliminates the risk of graft vs. host disease.
In her previous research, Mikkola and collaborators in
Harvard and France had discovered that the placenta
contained a large pool of blood stem cells, but it wasn’t
clear if they originated elsewhere and migrated to the
placenta to self-renew. Using a unique mouse model,
a mouse embryo without a heartbeat, Mikkola and
her team were able to find the blood stem cells at the
site of their origin because there was no circulation of
blood through the body.
“Using this model, we identified that the placenta has
the potential to make hematopoietic (blood) stem cells
with full differentiation ability to create all the major
lineages of blood cells,” Mikkola said. “The placenta
acts as a sort of kindergarten for these newly made
blood stem cells, giving them the first education they
need.”
“The labyrinth is a source of many growth factors and
cytokines,” Mikkola said. “We just need to identify
what those signaling molecules and cues are that are
nurturing those cells when in the placenta.”
Mikkola is confident the study can be confirmed in
humans. “Everything we’re learning suggests we will
find the same thing in the human placenta,” she said.
See more: http://www.sciencedaily.com/
releases/2008/03/080305121006.htm
Significantly Higher Success Rates with Artificial
Insemination Using New Ova Assessment Tool
ScienceDaily (Feb. 12, 2008)
Trying to conceive with fertility technology? A new
method could help some couples who are childless
against their will. The microscopic procedure
significantly improves the success rate of ‘ICSI’
(intracytoplasmic sperm injection). This was discovered
by scientists at the University of Bonn together with
colleagues from China and industrial partners in a
study of 124 women. Up to now, the desire to have a
child is only fulfilled for every third couple that decides
to have ICSI. In a study the artificial insemination
method was twice as successful.
For many couples ICSI is the last resort in their
attempt to have a child. ‘The method is recommended
if the man produces too few sperm cells,’ the Bonn
reproductive biologist Dr. Markus Montag explains.
Doctors can in most cases still extract individual
functioning sperm cells from testicular tissue, which
they then inject into the ovum. The partner must take
hormone preparations before an ICSI. They result in
several ova maturing in the ovaries, normally it is only
one ovum per month.
‘We inject a sperm into every one of these cells,’
Markus Montag explains. ‘Then it takes more than 26
hours until the plasmosomes of the ovum and sperm
cell fuse and an embryo forms. In this time frame we
have to decide which of the fertilized ova to insert into
the uterus.’ The reason for this is that the German
law for the protection of embryos lays down that only
a maximum of three fertilised ova are allowed to be
implanted per attempt. ‘We even restrict ourselves to
only two, in order to exclude the possibility of births of
triplets,’ Markus Montag explains. With pregnancies
involving multiple births there is an increased risk of
miscarriages and malformations.
Choosing the ‘best’ ova
Which of the fertilized ova are finally implanted has
usually been left up to chance. But today it is known
that not all ova have the same quality. Using a special
procedure the Bonn scientists can select the two most
suitable candidates. ‘For this we observe the ovule
integument under a DIC microscope,’ Dr. Montag
explains. ‘There it appears as a luminescent orangered
ring. The brighter this ring is and the more uniformly
it shines, the greater the chance that it becomes a
child.’ The reason for this is that the ovule integument
always seems to have a particularly uniform structure
if the cell has matured under good conditions.
Normally every third ICSI is successful. But if medics
used two ‘good ‘ ova in their experiment, this rate
increased to more than 50 per cent. With a ‘good’
and a ‘bad’ ovum the success rate was still around
40 per cent, using two ‘bad’ ones only 20 per cent.
‘Mind you, two “good” ova are rare,’ Markus Montag
emphasises. ‘Only with two out of ten cells does the
ovule integument have an intense regular orange
color.’
Under natural conditions insemination takes place in
the oviduct. After that the ovum begins to divide, while
contractions of the oviduct transport it to the uterus.

This process takes just under 2-3 days. When the
embryo lodges in the endometrium on the sixth day
after insemination, the embryo consists of several
hundred cells. During the whole process the embryo
is protected by the ovule integument.
The Bonn team led by Dr. Markus Montag and
Professor Hans van der Ven has developed software
in conjunction with the Octax Microscience Company,
which analyses the image from the microscope
objectively and proposes the most suitable cells. ‘This
way the procedure can be implemented in clinical
routine without problems and without much effort,’ he
says.
The scientists have now published their data in the
journal ‘Reproductive BioMedicine Online ‘. version
available at: http://www.rbmonline.com/Article/3161
Reference: http://www.sciencedaily.com/
releases/2008/02/080206102412.htm
9 th
Royan
International Research Award
Aug 27 – 29, 2008
Reproductive Biomedicine & Stem Cells
Biology & Technology
Deadline 10 April 2008
E-mail: Info@RoyanInstitute.org
AGOS 2008
American Gynecological and Obstetrical
Society
10-20 Sep., 2008
Carlsbad, CA, USA
Royan
International Twin
Congress
9th Congress on Reproductive
Biomedicine
4th Congress on Stem Cells Biology &
Technology
Aug 27-29, 2008 - Tehran - Iran
In Collaboration With: European Society
of Human Reproduction and Embryology
(ESHRE)
Middle East Fertility Society (MEFS)
British Andrology Society (BAS)
Asia Reproductive
Biotechnology Society
(ARBS)
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We will glad to see you in our Congress
27-29 Aug 2008, Tehran - IRAN
Please Smile,,,
If you want to have our newsletter for your
friend, let us know by
Info@RoyanInstitute.org
Fertility Society of Australia - Annual
Meeting 2008 20 – 22 Oct., 2008
Location: Brisbane, Australia