If you want the brightest clues about what's causing a good portion of the autism epidemic, set aside a few hours and watch these. More info on the conference is at the event website, autismepigenetics.org.
Presenter: Jill Escher
Affiliation: Escher Fund for Autism
Date: March 22, 2013
Length: 13:04
Summary: A mother of two
children with autism poses the question whether past exposures,
particularly prenatal exposures to popular mid-20th century prenatal
pharmaceutical drugs, such as synthetic steroid hormones and sedatives,
may have impacted vulnerable fetal germline epigenetics, resulting in a
surge of developmental abnormalities in the grandchild generation.
Presenter: Tracey Woodruff, Ph.D., MPH
Affiliation: Program on Reproductive Health and the Environment, UCSF
Date: March 22, 2013
Length: 22:47
Summary: We are experiencing a
sharp upward trend in autism that cannot be fully explained by factors
such as younger ages at diagnosis, migration patterns, changes in
diagnostic criteria. Interaction among environmental factors,
including a glut of novel and untested synthetic chemicals known to
cause disturbances in CNS development, may be contributing to the
problem. Dr. Woodruff explains the history of environmental chemical
exposures and efforts that were successful in reducing exposures and
improving child health.
Presenter: Dana Dolinoy, Ph.D.
Affiliation: University of Michigan School of Public Health
Date: March 22, 2013
Length: 30:00
Summary: Molecular level
epigenetic “switches” can influence the expression of protein-coding
genes. Periods of particular epigenetic susceptibility include
gametogenesis, pre-implantation stage of embryogenesis, fetal and
neonatal periods of development, puberty, ad old age. Lab studies have
shown endocrine-disrupting chemicals can have non-monotonic effects,
differentially methylate DNA (both hyper- and hypo), and have different
effects in different succeeding generations. Epigenomic studies can
decipher the role of the environment on the epigenome, identify
epigenetically labile genes, and link epigenetically labile loci with
biological pathways and phenotypes/human health outcomes.
Presenter: David Crews, Ph.D.
Affiliation: Section of Integrative Biology, University of Texas at Austin
Date: March 22, 2013
Length: 27:45
Summary: As an evolutionary
biologist, Dr. Crews’ research focuses on how exposures change
adaptation across generations in a sex-dependent way. He describes two
types of ways in which the environment sculpts the phenotype of
individuals: 1) context dependent which is due to a direct exposure and
manifests in each generation and 2) germline dependent. This manifests
in the absence of a causative agent since it is cumulative across
generations. He describes experiments where changes to the environment
can affect social and sexual behavior, as well as response to stress,
when the exposures was ancestral.
Presenter: Michael Skinner, Ph.D.
Affiliation: Washington State University
Date: March 22, 2013
Length: 40:32
Summary: Biological science is
undergoing a paradigm shift away from the fixed genetic determinism of
the 20th century and toward an understanding that environmental factors
can alter gene expression and activity. Genetics works together with the
environment to contribute to disease risk. In some cases, changes to
gene expression in future generations can occur when the germ cell
(sperm or egg) is reprogrammed via an abnormal exposure such as an
endocrine-disrupting compound, and these alterations may persist for
generations. This transgenerational exposure to environmental factors
represents an example of epigenetic inheritance. Various pathologies
may result from certain germline exposures, including cancer,
infertility, polycystic ovary disease, obesity, and behavioral
abnormalities. Assays find clusters of altered gene expression dependent
on the original exposure, or dependent on the generation studied.
Presenter: Amander Clark, Ph.D.
Affiliation: UCLA
Date: March 22, 2013
Length: 19:12
Summary: During pregnancy,
three generations of DNA coexist in the woman’s body: hers, that of her
fetus, and the primordial germ cells growing within the fetus. Those
germ cells decades later contribute to the grandchild generation. Human
gametogeneis begins in early gestation, with the male fetus’s germline
developing differently than the female fetus’s germline. The proper
reprogramming of the germline is essential for proper child development,
and molecular perturbations can lead to developmental disorders.
Environmental exposures can interfere with the molecular process of
germline programming.
Presenter: M. Danielle Fallin, Ph.D.
Affiliation: Johns Hopkins Bloomberg School of Public Health
Date: March 22, 2013
Length: 26:24
Summary: Various epigenetic
mechanisms may contribute to ASD traits and there is growing evidence
for environmental susceptibility of epigenetic marks. Studies show that
phenotype and epigenetic marks can be modified by factors such as
maternal diet, pharmaceuticals, and smoking, and metals and behavior.
The epigenome may be the intermediary between genetics and the
environment, mediating disease outcome. Existing research supports a
role for epigenetics in ASD etiology, for example with ASD-related
disorders with known epigenetic mechanisms, parent-of-origin effects,
differences of expression in ASD-related genes, and differences in
methylation patterns.
Epigenetic inheritance of complex behaviors and their alteration by traumatic stress in mammals
Presenter: Prof. Isabelle Mansuy
Affiliation: Brain Research Institute, University of Zurich
Date: March 22, 2013
Length: 30:34
Summary: Disease arises via a
combination of genotype and epigenotype. Over the human lifecycle, there
are different environmental influences on epigenotype. Early trauma is a
risk factor for psychiatric and cognitive disorders, and involve
epigenetic factors. Animal studies show early trauma can alter social
behavior across generations. Multiple molecular mechanisms appear to be
involved with the induced differences in gene expression, including DNA
methylation, histone/protamines posttranslational modifications, and
small noncoding RNAs.
Presenter: Andrea Gore, Ph.D.
Affiliation: University of Texas at Austin
Date: March 22, 2013
Length: 43:34
Summary: Hormones play a
critical role in sculpting the entire nervous system and brain.
Endocrine disrupting chemicals can adversely affect fetal brain
development and may have lifelong consequences. Psychiatric disorders
are influenced by gonadal steroid hormones. EDCs perturb hypothalamic
development and therefore hormonal regulation. Studies of PCBs, which
persist in the environment and bioaccumulate in tissue demonstrate
lifelong changes in physiology, brain development and behaviors.
Multigenerational adverse impacts of exposure to the antimiscarriage
synthetic hormone DES is also discussed.
Presenter: June Reinisch, Ph.D. and Erik L. Mortensen, CanD
Affiliation: University of Copenhagen Prenatal Development Project
Date: March 22, 2013
Length: 31:39
Summary: Historically, the
placenta was viewed as a barrier preventing passage of harmful
substances to the fetus. However, today we know that organ acts more
like a sieve, with most maternally ingested substances reaching fetal
tissues. Prenatal use of synthetic medications goes back a century,
beginning with barbiturates and then synthetic hormones, including
synthetic estrogens (including the catastrophic drug DES) progesterones,
and corticosteroids. In the mid 20th century, synthetic hormone drugs
were widely used in pregnancies deemed to be “at risk,” and as a result
millions of offspring were exposed to augmented levels of synthetic or
natural hormones. The exposures are associated with a variety of
disruptions of typical development; however, drug impacts on fetal germ
tissues (grandchild, or F2, generation) have not yet been assessed. A
study using the Danish Prenatal Development Project, which is unusually
rich with prenatal exposure data, will be the first to examine potential
germline/F2 impacts of prenatal drug use.
Presenter: Rosanna Weksberg, M.D., Ph.D.
Affiliation: University of Toronto
Date: March 22, 2013
Length: 23:58
Summary: Exposures are most
likely to have a significant impact only during certain stages of
development, including gamete development and early embryonic
development. Assisted reproduction, such as ovulation stimulation, in
vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI),
expose gametes and the early embryo to unusual environmental factors
coinciding in time with critical windows of epigenetic programming.
Exposures that may cause epigenetic perturbations include: ovulation
stimulation (FSH/clomid) (causing maturation and ovulation of oocytes
with incomplete/aberrant DNA methylation); IVF (in vitro embryo
culturing may disrupt proper imprinting maintenance in oocyte and embryo
during global genome demethylation); ICSI (sperm with
incomplete/aberrant methylation bypass natural selection). The increased
incidence of imprinting disorders associated with ART appears to arise
from epigenetic rather than genetic defects. Methylation patterns in ART
children appear to be slightly but significantly reduced. Study of
children conceived through ART offer a unique opportunity to study
exposure and epigenetic factors in development.
Presenter: Emilie Rissman, Ph.D.
Affiliation: University of Virginia
Date: March 22, 2013
Length: 23:58
Summary: Studies on
exposure-induced changes in social behavior in mice may shed light on
human neurobehavioral disorders. A study found that low-dose endocrine
disrupting chemical BPA changes juvenile interactions in female mice;
some changes in gene expression were also found. Multigenerational
effects were identified, with different effects in different
generations. Environmentally induced epigenetic modification of the X
chromosome may have implications for the sex difference seen in ASD.
Presenter: Janine LaSalle, Ph.D.
Affiliation: Medical Microbiology and Immunology, UC Davis School of Medicine
Date: March 22, 2013
Length: 30:21
Summary: A study on PBDEs
(flame retardant chemical) and PCBs (industrial chemical) examined the
effects of environmental pollutants on epigenetics of neurodevelopment
in both a mouse model and with human brain tissue. Perinatal BDE-47
exposure adversely affected reproductive success in this genetically
susceptible mouse model, consistent with adverse effects on human
fecundity. PBDE exposure adversely affected two measurements of social
behavior in the mouse model, and resulted in reduced global DNA
methylation in the adult brain specifically in females, correlating with
deficits in sociability. Gene by environment interactions at the
epigenetic interface are complex, involving sexual dimorphism,
epigenetic dysregulation, compensatory molecular mechanisms, and
specific behavioral deficits. The study of PCBs in human brain samples
suggested a possible environmental contributor to 15q duplications
through an epigenetic mechanism. An integrative approach to
understanding environmental impacts on the brain methylome is suggested.
Presenter: Adam Urato, M.D.
Affiliation: Chairman, Dept. of OB/GYN, MetroWest Medical Center, Assistant Professor, Tufts Medical Center
Date: March 23, 2013
Length: 29:23
Summary: Medication use during
pregnancy is common and has been steadily increasing since the 1970s;
typical pharmaceuticals include antidepressants, anti-nausea drugs, and
heartburn medications. This represents a dramatic change in the chemical
environment from the perspective of evolutionary biology: mammals have
evolved for 200 million years without the interference of synthetic
drugs in gestation. In spite of clear warning signs, the synthetic
estrogen drug DES was used on pregnant women for 33 years before the
harmful effects were acknowledged. Today, prenatal use of SSRI drugs has
surged since their introduction in the 1980s. Studies in animal models
and human cohorts suggest that fetal SSRI exposure may long-term
neurodevelopmental outcome, including reports of an increased risk for
ASD.
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