our ancestors’ ghosts: ancestral exposure to stress ...ancestral exposure to stress epigenetically...
TRANSCRIPT
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Our Ancestors’ Ghosts: Ancestral Exposure to Stress
Epigenetically Programs Preterm Birth Risk and Health Outcomes
Gerlinde A. S. Metz
Canadian Centre for Behavioural Neuroscience University of Lethbridge Alberta, Canada
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Programming of the
Stress Response
Woods et al., AJOG, 2010
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Stress generates a footprint that
travels
from one generation to the next…
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Stress generates a footprint that
travels
from one generation to the next…
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HYPOTHESIS: Ancestral Stress
Programs Maternal and Offspring
Health Trajectories
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HYPOTHESIS: Ancestral Stress
Programs Maternal and Offspring
Health Trajectories
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Does Stress Program Maternal
and Offspring Health?
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Gestational Stress Disrupts
Maternal Behaviour
Zucchi et al., PLoS ONE, 2013
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Can Stress During Pregnancy
Influence Preterm Birth Risk?
No Change in Gestational Length…
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> 80 genes
involved in
neurological
diseases and
mental illness
Prenatal Stress Programs Gene
Expression Patterns
Zucchi et al., PLoS ONE, 2014
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Zucchi et al., PLoS ONE, 2013
Gestational Stress Alters
Potentially Heritable Epigenetic
Markers
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Can Stress Effects Propagate
to the Next Generations?
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Can Stress Effects Propagate
to the Next Generations?
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Can Stress Effects Propagate
to the Next Generations?
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Can Stress Effects Propagate
to the Next Generations?
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Unstressed Multigenerational
(S,SS, SSS, SSSS)
Transgenerational
(S, SN, SNN, SNNN)
Model of Transgenerational Maternal Stress
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Ancestral Stress
Shortens Gestational Length
540 hrs. 529 hrs. 527 hrs.
Yao et al., BMC Medicine, 2014
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Ancestral Stress Elevates
Blood Glucose Levels
Yao et al., BMC Medicine, 2014
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Ancestral Stress Regulates the
miR-200 Family: Role in Pregnancy
Maintenance
Yao et al., BMC Medicine, 2014
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miR-200 Family Regulates Genes
Involved in Pregnancy
Maintenance
Yao et al.,
BMC Medicine, 2014
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Placental microRNA Signatures
as Proxies for Brain and Uterine
Health
F3 F3 F2 F2 F1
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Babenko, Kovalchuk et al., unpublished data
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?
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Ancestral Stress Impedes
Offspring Development
Yao et al., BMC Medicine, 2014
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Ancestral Stress Impedes
Offspring Development
Yao et al., BMC Medicine, 2014
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Erickson et al., PLOS One, 2014
Ancestral Stress
Alters Behaviour During
Vulnerable Periods in Life
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Remote Ancestral Stress Shifts
Patterns of Complex Diseases
Ambeskovic et al., unpublished data
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Can Beneficial Experience
Offset Adverse
Programming?
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Environmental Enrichment
Mitigates Adverse
Programming by Stress
McCreary, Erickson, et al., unpublished data
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McCreary, Erickson, et al., unpublished data
Environmental Enrichment
Mitigates Adverse
Programming by Stress
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Ancestral Stress May Better
Prepare Future Generations
?????
Benefits
• Resilience
• Metabolic
Preparation
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Ancestral Stress
Also Bears Health Risks
?????
Benefits
• Resilience
• Metabolic
Preparation
Risks
• Cardiovascular
• Metabolic
• Aging
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Benefits
• Resilience
• Metabolic
Preparation
Risks
• Cardiovascular
• Metabolic
• Aging
Transgenerational Programming
of Maternal and Offspring Health
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Benefits
• Resilience
• Metabolic
Preparation
Risks
• Cardiovascular
• Metabolic
• Aging
Transgenerational Programming
of Maternal and Offspring Health
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Building the Foundation for Healthy Futures
• Ancestral stress is a significsnt influence on lifetime health trajectories.
• Transgenerational inheritance involves epigenetic mechanisms.
• Transgenerational studies may identify new predictive biomarkers of disease.
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Acknowledgements University of Lethbridge
Canadian Centre for Behavioural Neuroscience
Dr. Bryan Kolb
Tony Montina
Dept. of Biol. Sciences
Dr. Igor Kovalchuk
Dr. Olga Kovalchuk
• Dr. David M. Olson (University of Alberta)
• Dr. Suzanne King (McGill University)
Alberta Innovates
Health Solutions
Alberta Innovates
Health Solutions
Alberta Innovates
Health Solutions
Alberta Innovates
- Health Solutions
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Questions?
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Does Stress
Induce
Genuine
Trans-
generational
Effects?
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Programming of the
Stress Response
Great Great Grandmother
Great Grandmother
Grandmother
Mother
YOU!
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Proposed Mechanisms of
Action of miR-200
Proposed mechanisms of action of miR200, ZEB1,2
and STAT5b - Carole Mendelson Lab
Williams et al., PNAS, 2012; 109:7529-34
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Transgenerational Epigenetic
(microRNA) Programming of
Cortical Development
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Babenko, Kovalchuk, et al., unpublished data
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Down-Stream Metabolic
Signatures of Stress
Example: F3-SNN Kiss, Montina, et al., unpublished
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Ambeskovic et al., 2013
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Metabolic Signatures of
Age-related Diseases in Hair
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HYPOTHESIS: Ancestral Stress
Programs Maternal and Offspring
Health Trajectories