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synthetic media for considerable lengths of time (cell generations),
because speci
c epigenetic changes such as loss of expression of the
OCT 4 gene occurs in these cultures (Buehr et al. 2003; Wang et al. 2013).
These cells thereby retain their pluripotent status after numerous divi-
sions. Using homologous recombination to disrupt single gene function,
the cultured single gene knockout ICM cells can be transplanted back
into blastocysts and will continue to develop into genetic chimeras. This
is the technique that allowed the ef
cient production of gene knockout
mice (Evans and Kaufman 1981; Martin 1981) and revolutionized animal
genetic studies. Because of epigenetic changes related to the culture
environment, ICM cells also can result in aberrant embryo development
when transplanted back into developing blastocysts (Dean et al. 1998;
Humphreys et al. 2001). This is undoubtedly the result of inappropriate
epimarks in the transplanted nucleus (Jaenisch and Gurdon 2007) and
also likely often re
ects changes in imprinted loci since they strongly
control embryo/fetus growth rate. The evolutionary culmination of the
in-body, highly homeostatic environment of mammals for full-term
embryo development may re
ect a need to reproduce epigenetic status
during development at a very high level of
fidelity. This could be
required as part of the strategy of mammals to deal with environmental
challenges with a behavioral or even socio/cultural approach. Behavior
and cultural abilities undoubtedly necessitate extensive intricate and
highly accurate epigenetic processes (Avital and Jablonka 2000). Some
of the most frequent epigenetic aberrations that occur during human
embryo development are manifested in neurological, cognitive, and
behavioral disorders (Dulac 2010). It is more than coincidental that
the culturing of plant cells in arti
cial media also frequently results
in aberrant development in plants that are regenerated from such cells
(Larkin and Scowcroft 1981; Miguel and Marum 2011) just as more
recently observed in cultured mammalian ICM cells.
Although it is now clear that pluripotent cells of both plants and
animals appear to be vulnerable to abnormal and perhaps environment-
directed epigenetic changes (Jablonka and Raz 2009; Grafi
et al. 2011),
many aspects and components of the mechanisms of the alterations
remain elusive (Matzke and Scheid 2007). It is most likely that the most
important factor for
fidelity of transgenerational inheritances of either
Mendelian- or epigenetic-based traits is the number of cell divisions that
occur between fertilization and meiosis. The female germ lineage usu-
ally undergoes very few divisions, especially in mammals, producing a
small number of gametes, compared with the male line. This is undoubt-
edly related to differences in male and female reproductive strategies as
described in the con
ict theory (Moore and Haig 1991). Time between
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