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SCIENTIFIC PROGRAM • SYMPOSIA
Monday, October 17, 2011 4:15 pm – 6:15 pm
Scientific Program Committee Symposium
NUTRITION, DIET AND EPIGENETIC CHANGES PRIOR TO AND
AFTER CONCEPTION
Kelle H. Moley, M.D. (Chair)
Washington University in St. Louis
Carmen Sapienza, Ph.D.
Fels Institute for Cancer Research
Rebecca A. Simmons, M.D.
University of Pennsylvania School of Medicine
Needs Assessment and Description
Maternal nutrition, diet and environmental exposure have
long been known to have lasting effects on offspring and
this phenomenon has been coined Developmental Origins
of Health and Adult Diseases (DOHAD). Although the
mechanisms responsible for this event are not entirely clear,
dysregulation of the epigenome as well as alteration in
genomic imprinting may play an important role and provide
a putative explanation for how changes in gene expression
as early as the gamete stage are heritably maintained
through cell division in animals throughout life.
Genomic imprinting is a process by which monoallelic
expression of some specific genes in the diploid cells is
dependent on whether the allele is transmitted from the
sperm or from the oocyte. This epigenetic mechanism
renders the parental genomes functionally unequal. To
date, about 40 imprinted genes have been identified, some
of which have been shown to be involved in embryonic
development and growth, placental differentiation,
suppression of tumorigenesis, behavior, and genetic
disorders, respectively. Although little is known of the
imprinting mechanisms, it is believed to be a multistep
process. First, an imprinting signal for distinguishing the
parental origin of the alleles in the embryo is constructed
during gametogenesis of the parents. This process refers
to a primary or gametic imprinting. Second, the imprinting
signal on each gene is maintained after fertilization and
leads to allele-specific gene expression until around the time
of gastrulation. Third, this regulatory expression is sustained
in the somatic cells throughout embryonic development,
whereas the signals are erased in the germ cells.
Animal models and human studies of dietary and
nutritional changes prior to and during pregnancy have
shown detectable changes in overall DNA methylation,
and alterations in methylation state in specific regions
of imprinted genes, such as the IGF2 receptor gene that
controls normal embryonic development. These three
presentations will highlight maternal dietary, environmental
and related fetal epigenetic changes that can occur in
response to changes in maternal diet and nutrition and that
determine size and the development of disease states in the
offspring.
Room 224 E/F
68
Learning Objectives
At the conclusion of this session, participants should be able
to:
1. Identify different mechanisms of dietary-induced
epigenetic alterations in the diplotene oocyte and the
developing fetus, as well as epigenetic determinants of
birthweight.
2. Recognize how preconception high fat feeding perturbs
primary imprinting during oocyte growth and plays a
critical role in both the expression and repression of
maternal alleles during embryogenesis.
3. Describe how maternally-induced fetal growth restriction
leads to epigenetic changes resulting in offspring with
type 2 diabetes.
4. Explain how epigenetic signatures are linked to infant
birthweight.
ACGME COMPETENCY
Medical Knowledge
TEST QUESTION:
Which one of the following best describes the effect of
maternal nutrition and environmental exposure on outcome
of offspring?
A. No scientific evidence exists to strongly recommend
weight loss and dietary changes prior to pregnancy in
order to improve the lifelong health of the infant.
B. Nutritional alterations during the oocyte growth phase
can perturb DNA methylation and have lasting effects
on offspring outcomes.
C. Birthweight has no effect on lifelong health status in the
child and this may be independent of traditional
Mendelian genetics.