SINGAPORE - Singapore scientists have discovered that a protein
present in the mother's egg is essential for the survival of a newly formed
embryo, and the lack of this protein in some mothers may explain events of
multiple miscarriages.
Using genetically identical mice, the researchers led by scientists at
A*STAR's Institute of Medical Biology (IMB) discovered that none of the embryos
from the fertilisation of eggs lacking the protein TRIM28 survived.
The embryos died at varying stages of development and was observed to
have a range of developmental defects.
This allowed the scientists to discover that the timing and amount of
this protein made available to the newly formed embryo right after
fertilisation greatly impacts the expression of imprinted genes at later
developmental stages.
Imprinted genes are genes expressed in a parent-of-origin-specific
manner.
While most of the expression of heritable traits from the mother and
father is erased from the DNA passed on from the sperm and egg cells, some of
these 'epigenetic marks' have to be preserved for the survival of the embryo.
The essential protein thus works to preserve the epigenetic marks of
imprinted genes.
Explained through an analogy by Dr Davor Solter of the Wistar Insitute,
a pioneer of genomic imprinting, he described a scenario of a teacher writing a
long string of formulas on a black board. The protein is then what instructs
the 'cleaning lady' on which parts of the formulas she should preserve.
This finding that finally reveals why certain bits of the DNA formula
escapes reprogramming is especially important in the field of in vitro
fertilisation of eggs for the treatment of infertility.
However, it also sheds a light on the importance of epigenetic
mechanisms in development and disease, said Dr Azim Surani of Cambridge
University, another pioneer in genomic imprinting.
Dr Barbara Knowles, the senior author of the paper said: "Lack of
TRIM28 in their eggs could explain why some women consistently suffer from
multiple failed pregnancies where embryos die at different time points,
manifesting multiple, different abnormalities."
It is expected that the study will have far-reaching clinical implications
for treatments using patient specific cell therapies, thus opening new avenues
of formulating medical strategies, said Professor Birgitte Lane, Executive
Director of IMB.
AsiaOne
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