Fetal Origins of Disease Flashcards
1
Q
In addition to protein-energy under-nutrition, the fetus is sensitive to: [5]
A
- Over-nutrition (e.g., maternal diabetes)
- Low supply of specific nutrients (e.g., methyl donors, iron)
- Imbalanced nutrition (e.g., high fat)
- Maternal stress
- Maternal care (this point does not fit within the original fetal origins of disease hypothesis)
2
Q
Describe the risk of developing youth-onset type 2 diabetes according to birth weight.
A
- Risk is increased with both low and very high birth weights (> 4kg)
- Suggests maternal under and over nutrition is important
3
Q
What were the results of this study where rats were fed “balanced diet” or “junk food diet” rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence.
A
4
Q
Describe the fetal origins hypothesis.
A
- Risk for chronic disease may be influenced by the environment the fetus experiences in utero
- Poor maternal/fetal nutrition (under/over/imbalanced) or high maternal stress during pregnancy can affect likelihood that offspring will experience health challenges later in life
5
Q
The fetal origins hypothesis is based on concepts of developmental plasticity and programming.
Define: developmental plasticity.
A
- Particular genotype may produce different phenotypes depending on environmental exposures
- Organs and systems adapt to cues (i.e., epigenetics)
- “Plasticity during intrauterine life enables animals, and humans, to receive a “weather forecast” from their mothers that prepares them for the type of world in which they will have to live”
6
Q
The fetal origins hypothesis is based on concepts of developmental plasticity and programming.
Define: programming.
A
- Stimuli in early development lead to changes that are permanent (persistant across lifespan) (i.e., epigenetics)
7
Q
Describe: ‘thrifty phenotype’
A
- Early under-nutrition can program the offspring to survive in a nutrient-poor environment
- Smaller size, decreased energy expenditure, increased fat storage, increased appetite
- However, when the offspring is exposed to a nutrient rich environment after birth, the mismatch between the fetal and postnatal environments leads to increased risk for chronic disease
8
Q
Describe the results of this study:
* Pregnant rats fed either ad libitum (AD) or undernutrition (30% of AD calories) during gestation and lactation
* After weaning, offspring from both groups were given either control or hypercaloric (high fat) diet
A
- UN animals remain shorter as adults, but exhibit increased fat mass compared to AD animals.
9
Q
What are 2 possible mechanisms for early programming?
A
- Structural/functional effects (altering organ development or function)
- Epigenetics
10
Q
Define: critical period.
A
- Fetal growth and development proceeds through a series of “critical periods” = a specific time period during which the cells of a tissue (or organ) are genetically/epigenetically programmed to multiply
- If proper growth and development does not take place during this period, it can not be made up for later
- Most critical periods occur early in pregnancy
11
Q
Give examples of structural programming that occurs during a critical period.
A
- Malnutrition during development of kidney leads to reduced renal volume and nephrons which leads to hypertension
- Malnutrition during development of pancreas leads to reduced beta-cells and impaired insulin secretion
12
Q
Describe epigenetic programming in fetal origins of disease.
A
- Epigenomic changes lead to permanent gene expression changes and phenotypic effects later in life.
13
Q
Name 4 components of the epigenome.
A
- Methylated CpG site
- Non-methylated CpG site
- Histone methylation
- Histone acetylation
14
Q
Describe which nutrients are important in epigenetics [7] and why.
A
- SAM is needed for methylation
- SAM synthesis requires many nutrients:
- Folate
- B6
- B12
- B2
- Choline
- Betaine
- Methionine
15
Q
Describe the Agouti Gene - animal model.
A
- Agouti gene: development of coat color
- The A^vy gene variant leads to yellow coat color and predisposition to obesity
- Methylation of the A^vy gene determines whether mice develop normal or yellow coat
- These mice (right) are genetically identical, but differ in methylation at the agouti gene
- Depending on the timing and level of methylation, 5 various phenotypes are possible.
16
Q
Baed on the results of the previous figure, it appears that the yellow coat phenotype is expressed when the gene is […]
A
Un-methylated
17
Q
Describe factors influencing fetal predisposition to diabetes. [2]
A
- Malnutrition during pregnancy (LBW) = epigenetic silencing of Pdx1 in pancreas
- Gestational diabetes = epigenetic silencing of leptin
18
Q
Describe how gestational diabetes increases risk of type 2 diabetes in offspring.
A
- Decrease in expression through hypermethylation of leptin gene
19
Q
Describe: Project Ice Storm
A
- METHODS: Studied DNA methylation patterns in white blood cells & saliva cells from offspring born to mothers pregnant during the 1998 ice storm [and correlated this with maternal “stress”]
- RESULTS: DNA methylation changes highly correlated with maternal objective stress
- CONCLUSIONS: Prenatal maternal stress results in a lasting, broad, and functionally organized DNA methylation signature in several tissues in offspring.
20
Q
What contributes to fetal programming? [2]
A
- Genetic factors
- Environmental factors
21
Q
What does the Barker Hypothesis state?
A
- The fetal origins hypothesis states that fetal under-nutrition leads to disproportionate getal growth, programmes later coronary heart disease.
22
Q
Define LBW.
A
- Low birth weight
- <2.5 kg (<5.5lbs) at birth
- Small for gestational age (SGA)
- Preterm: <37 weeks
- Increased risk for infection, learning disabilities, impaired physical development, death in first year
- Fetal origins hypothesis suggests LBW also increases risk for chronic disease later in life
23
Q
Discuss the importance of maternal nutrition.
A
- Nutrition is one of the most important modifiable variables leading to birth of mature (term) infant with normal birth weight
- Poor maternal nutrition = increased risk of LBW
- LBW = increased likelihood of health challenges later in life
- Poor maternal nutrition may increase likelihood that offspring will experience health challenges later in life.
24
Q
What is ‘the Hongerwinter’?
A
- Nazi blockage of food transport during their occupation of the Netherlands in the winter of 1944-45; rations reduced to as little as 500-800 kcal/day.
- More than 20,000 people died, some survived by eating tulip bulbs and adding paper to soup
- Excellent health records available
25
Describe the results of the 'Hongerwinter' cohort.
* Fetal undernutrition, particularly early in gestation, associated with increased risk of numerous health problems later in life.
26
Which chronic diseases are associated with fetal origins of adult disease?
* Diabetes
* Obesity
* Dyslipidemia
* Hypertension
* Coronary artery disease
* Stroke
* Kidney failure
* Liver failure
* Lung abnormalities
* Immune dysfunction
* Reduced bone mass
* Alzheimer's Disease
* Depression, anxiety, bipolar, schizophrenia
* Cancer
27
Discuss maternal care and epigenetic programming.
28
Discuss childhood abuse and epigenome.
29
Parental experiences do not impact the epigenome of next generations.
True or False?
False.
Both maternal and paternal affect the epigenome of next generations.
30
Parental experiences impact the epigenome of next generations.
True or False?
True.
Both maternal and paternal.
31
Discuss how low paternal dietary folate changes the sperm epigenome.
32
Discuss how a high-fat paternal diet can affect offspring.
* Increased risk of diabetes.
33
Describe how paternal olfactory experience affects offspring.
34
What 4 factors influence the epigenetic remodelling of the brain, pancreas, liver, and other organs of a fetus?
## Footnote
And therefore its behaviour, mental, and physical health.
* Parental diet & diet during pregnancy
* Maternal care
* Early life experiences
* Parents/grandparents life experiences
35
The fetal origins of adult disease (FOAD) hypothesis was introduced based on the pioneer findings by Dr. [...]
Dr. David Barker
36
What are the processes/mechanisms that can explain the fetal origins hypothesis? [3]
* Developmental plasticity and programming
* Altering organ development and function
* Epigenetic regulation of gene expression
37
Regarding the fetal origins hypothesis: it says that risk for chronic disease may be influenced by the environment the fetus experiences in utero.
True or False?
True
38
Regarding the fetal origins hypothesis: it recognizes early postnatal life exposures as another sensitive period to shape human health later in life.
True or False?
True
39
Regarding the fetal origins hypothesis: it excludes paternal experiences as a factor that could influence health of the offspring.
True or False?
False.
