Biology Reference
In-Depth Information
5.13 Centrosomes in Embryonic Stem Cells
We have documented centrosomes in embryonic stem cells (ESCs), establishing
their role in cell division and cell polarity (Sathananthan et al.
2002
). These ESCs
are pluripotent, diploid, self-reproducing cells, derived from the inner cell mass
(ICM) of the blastocyst; they are capable of differentiating into all three germ
layers, thus to any cell type of the human body. They are also capable of spon-
taneous differentiation and in essence are somatic cells with typical centrosomes,
though with a much more simplified structure than ICM cells of blastocysts. This
we attributed to cell de-differentiation.
5.14 Problems with Cloning
One of the challenges of modern reproductive technology is therapeutic cloning
and reproductive cloning in mammals, including primates. Cloning or somatic cell
nuclear transfer (SCNT) into enucleated oocytes to produce blastocysts, ESC and
offspring has not been very successful, even in mice or monkeys (Sathananthan
2009
; Simerly et al.
2004
). There are evidently problems with centrosomal com-
patibility, cell cycle asynchrony, nuclear reprogramming, and genomic imprinting
after SCNT, where a diploid somatic cell is electro-fused with or injected into a
haploid enucleated oocyte and activated to develop. The oocyte is at metaphase II
of meiosis, while the somatic cell is at interphase of mitosis with two centrioles,
closely associated with its nucleus. Further, the oocyte centrosome is absent or
inactive, while the somatic centrosome is functional and forms the bipolar spindle
to initiate mitosis in the cloned cell. Abnormal MT formations were reported in
monkey SCNT constructs but not in the bovine constructs (Simerly et al.
2004
).
5.15 Conclusion and Future Directions
It is essential that the fundamental concepts of human fertilization and embryo-
genesis be clearly understood and applied to the new technologies of assisted
reproduction. We need to explore further centrosomal dysfunction in embryos
derived from poor quality sperm used in ICSI and follow these up during cleavage,
implantation, and in offspring. We need to identify sperm with possible centro-
somal defects in poor sperm samples with little or no motility, using specific
antibodies for proteins associated with sperm centrosomes, before sperm injection
by ICSI. Gamete aneuploidies and chromosomal defects, including DNA frag-
mentation, need to be closely monitored in assisted reproductive technologies
(ART), since they will contribute to abnormal embryo development. It must be
also
remembered
that
the
centrosome
and
chromosomal
cycles
are
closely
