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Early Human Embryos Make "Mistakes" as a Matter of Survival, Could be Key to Understanding Stem Cell Development

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Early human embryos may be naturally prone to making mistakes in chromosome allocation to new cells, according to a report by Bedford Stem Cell Research Foundation scientists. Their new findings indicate rapid increases in total genetic information may be more important to embryo survival than accurate allocation of genetic information to each new cell. These first time data come from 8-Cell stage human embryos that have

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									Early Human Embryos Make "Mistakes" as a Matter of Survival, Could be Key
to Understanding Stem Cell Development

Bedford, MA, April 07, 2010 --(PR.com)-- Early human embryos may be naturally prone to making
mistakes in chromosome allocation to new cells, according to a report by Bedford Stem Cell Research
Foundation scientists. Their new findings indicate rapid increases in total genetic information may be
more important to embryo survival than accurate allocation of genetic information to each new cell.

These first time data come from 8-Cell stage human embryos that have been examined for expression of
all human genes in a project designed to understand how human eggs remodel genetic information to
produce new cells with the potential to become all the cells in the body, in other words, how embryos
give rise to Embryonic Stem Cells.

The recent research focused on how early embryo cells multiply. Scientists at the Bedford Stem Cell
Research Foundation (www.bedfordresearch.org) compiled data from three prior reports by other
laboratories that examined in unprecedented detail the 3,803 genes (out of about 25,000, organized into
23 chromosomes) that are involved in the multiplication of adult human cells. To multiply, cells must
grow in size, duplicate their chromosomes from 23 to 46, then divide the chromosomes equally into two
new daughter cells. This is the process by which the body makes billions of cells every day, including
blood cells, intestinal cells, hair, and sperm.

When the subset of 3,803 cell division genes in the adult human cells were compared with those
expressed in the human embryo (at the 8-cell development stage, a stage every human embryo progresses
through about day three of development), Bedford Stem Cell Research Foundation scientists discovered
that key genes involved in slowing the process of cell division to ensure the integrity of new
chromosomes were silent in the 8-Cell embryo. Moreover, genes known to push cell division faster were
detected at much higher levels in the embryo cells. These data suggest early human embryo cells rapidly
multiply in the absence of checkpoints to insure the accuracy of allocation of genetic information to new
daughter cells.

“In light of these findings, we need to re-think the early human embryo,” said Dr. Ann Kiessling, lead
author on the paper. “Each and every cell may not be identical, as has generally been believed. Like all
mammals, human reproduction is designed to conserve maternal resources. Checks and balances are in
place to ensure that the mother does not nurture a fertilized egg that is not robust enough to develop into a
baby. The human egg appears mid-way from one menstrual cycle to the next. It must be fertilized within
a day or two, and it must signal the mother it is developing. The signal from the egg must be robust and
must increase every day for several weeks; failure to increase the signal results in a menstrual cycle and
expulsion of the failed egg.

“Therefore, it may be more important to the embryo's survival to increase the number of copies of the
genes that generate the signal to the mother than it is to take the time to ensure accurate chromosomes in
each daughter cell. Information from animal studies indicates when the embryo reaches the 16- to 32-cell
stage, most of the cells become committed to placenta, only a few will give rise to the baby. Therefore,


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only a few cells need to be chromosomally perfect to give rise to all the tissues in the body.

“But if no cells are chromosomally perfect, embryo development will fail. The embryo cells may have an
as yet undiscovered mechanism for ensuring some cells will be chromosomally perfect, perhaps related to
the circadian oscillators previously reported (circadian genes oscillate according to night/day cycles), or
they may possess undiscovered repair mechanisms.”

This new information indicates that not all cells in early human embryos are identical and provides a
possible explanation for several known facets of human egg biology. Genetic analysis of individual cells
from early embryos reveal frequent abnormalities in chromosome number. Successful derivation of
pluripotent stem cells from individual cells of early embryos is extremely rare, perhaps due to this
naturally occurring phenomenon of chromosomal abnormalities.

“These surprising findings need confirmation by additional studies. But they lay the groundwork for
specific experiments to improve the potential of human eggs. Studies of natural pregnancy rates suggest
only one in four fertilized human eggs have the capacity to develop to offspring, even fewer in older
women. The development of artificially activated eggs into parthenogenetic stem cell lines is also limited
to a small percentage.

“A full understanding of early human embryo cells is essential not only to help correct defects in early
development, but in order to understand the rest of human biology, especially what goes wrong, including
cancer, and how to harness the power of stem cells to multiply and regenerate tissues,” said Kiessling.

The work appeared on line today in the Journal of Assisted Reproduction and Genetics. Scientists at the
University of Athens School of Medicine, Athens, Greece participated in the study.

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Contact Information:
Bedford Stem Cell Research Foundation
Allison Kiessling
617-281-7902
allison@bedfordresearch.org
http://www.bedfordresearch.org


Online Version of Press Release:
You can read the online version of this press release at: http://www.pr.com/press-release/225419




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