5.

Disrupted epigenetic state, induced broadly by

environment - humans
Disrupted epigenetic reprogramming due to scientific/ medical intervention
Assisted reproductive technologies, cloning, somatic cell reprogramming
Influence of the environment on epigenetic control
Sensitive periods of exposure, requirement for mitotic heritability
Diet, maternal care, chemical exposure



5. Disrupted epigenetic state, induced broadly by
environment
Disrupted epigenetic reprogramming due to scientific/ medical intervention
Assisted reproductive technologies, cloning, somatic cell reprogramming
Influence of the environment on epigenetic control
Sensitive periods of exposure, requirement for mitotic heritability
Diet, maternal care, chemical exposure

(Transgenerational epigenetic inheritance through the gametes)
All topics controversial many mouse studies, few human





5. Disrupted epigenetic state, induced broadly by
environment
Disrupted epigenetic reprogramming due to scientific/ medical intervention
Assisted reproductive technologies, cloning, somatic cell reprogramming
Influence of the environment on epigenetic control
Sensitive periods of exposure, requirement for mitotic heritability
Diet, maternal care, chemical exposure

(Transgenerational epigenetic inheritance through the gametes)
All topics controversial many mouse studies, few human

What proportion of the genome is sensitive to the environment?
What proportion of people are sensitive to environmental disruption?
What proportion of changes are meiotically or mitotically heritable?


Disrupted epigenetic reprogramming
Assisted reproductive technologies (ART) e.g. IVF, Intracytoplasmic
sperm injection (ICSI)
Somatic cell nuclear transfer for cloning
Reprogramming of somatic cells to induced pluripotent stem cells
Disrupted epigenetic reprogramming in assisted
reproductive technologies
Not yet entirely clear the effect of ICSI or IVF on epigenetic reprogramming
Many studies show an increase in BWS and AS, particularly following ICSI
Human oocyte
ready for IVF
ICSI in process with
human samples
Disrupted epigenetic reprogramming in assisted
reproductive technologies
These cases of imprinting disorders result from epigenetic abnormalities
Angelman syndrome, Beckwith Wiedemann syndrome both maternally
transmitted
Imprinting disorders due to epigenetic anomalies are very rare (e.g.
1/300,000), and if increased (3-5 fold?), absolute risk low in ART children
Broader epigenetic abnormalities not necessarily disease-specific
Disrupted epigenetic reprogramming in assisted
reproductive technologies
What is the role of the fertility defect in producing any anomaly?
Maternal age, underlying defect that causes fertility problems?
Related epigenetic abnormalities in non-humans (cattle, mice) following
ART performed for husbandry reasons or experimentally
Procedural issue?

Disrupted epigenetic reprogramming in ART
Effect due to disruption during sensitive periods of epigenetic
reprogramming?
Early development
ICSI/ IVF
Culture in vitro (media)
Embryo handling
PGC and GC development
Germ cell harvest
Disrupted epigenetic reprogramming in ART
Altered maternal effect proteins due to oocyte harvest, and
erosion of DNA methylation imprints in early development?
Early development
ICSI/ IVF
Culture in vitro (media)
Embryo handling
GC development
Germ cell harvest
Acknowledgements
A human oocyte is held by a glass holding pipette (http://
commons.wikimedia.org/wiki/File%3AICSI.jpg) by Eugene
Ernmolovich (CC BY-SA 3.0) via Wikimedia Commons
"Stripped" human oocyte (http://commons.wikimedia.org/wiki/File
%3AOocyte.jpg) By ekem (courtesy of RWJMS IVF Laboratory)
[Public Domain] via Wikimedia Commons