Fetal Origins of Disease Flashcards
In addition to protein-energy under-nutrition, the fetus is sensitive to: [5]
- 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)
Describe the risk of developing youth-onset type 2 diabetes according to birth weight.
- Risk is increased with both low and very high birth weights (> 4kg)
- Suggests maternal under and over nutrition is important
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.
Describe the fetal origins hypothesis.
- 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
The fetal origins hypothesis is based on concepts of developmental plasticity and programming.
Define: developmental plasticity.
- 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”
The fetal origins hypothesis is based on concepts of developmental plasticity and programming.
Define: programming.
- Stimuli in early development lead to changes that are permanent (persistant across lifespan) (i.e., epigenetics)
Describe: ‘thrifty phenotype’
- 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
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
- UN animals remain shorter as adults, but exhibit increased fat mass compared to AD animals.
What are 2 possible mechanisms for early programming?
- Structural/functional effects (altering organ development or function)
- Epigenetics
Define: critical period.
- 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
Give examples of structural programming that occurs during a critical period.
- 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
Describe epigenetic programming in fetal origins of disease.
- Epigenomic changes lead to permanent gene expression changes and phenotypic effects later in life.
Name 4 components of the epigenome.
- Methylated CpG site
- Non-methylated CpG site
- Histone methylation
- Histone acetylation
Describe which nutrients are important in epigenetics [7] and why.
- SAM is needed for methylation
- SAM synthesis requires many nutrients:
- Folate
- B6
- B12
- B2
- Choline
- Betaine
- Methionine
Describe the Agouti Gene - animal model.
- 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.
Baed on the results of the previous figure, it appears that the yellow coat phenotype is expressed when the gene is […]
Un-methylated
Describe how gestational diabetes increases risk of type 2 diabetes in offspring.
- Decrease in expression through hypermethylation of leptin gene
Describe: Project Ice Storm
- 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.
What does the Barker Hypothesis state?
- The fetal origins hypothesis states that fetal under-nutrition leads to disproportionate getal growth, programmes later coronary heart disease.
Discuss the importance of maternal nutrition.
- 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.
Describe the results of the ‘Hongerwinter’ cohort.
- Fetal undernutrition, particularly early in gestation, associated with increased risk of numerous health problems later in life.
Discuss maternal care and epigenetic programming.
Discuss childhood abuse and epigenome.
Discuss how low paternal dietary folate changes the sperm epigenome.
Discuss how a high-fat paternal diet can affect offspring.
- Increased risk of diabetes.
Describe how paternal olfactory experience affects offspring.
