1B early environmental and biological impacts on lifelong health Flashcards
What challenges could foetus face in term that could have a lasting impact on its health?
- Foetal infection in utero
- Maternal illness
- Maternal stress
- Maternal nutrition
- Maternal medication
- Environmental factors/exposures
How does maternal nutrition affect a foetus?
High fat or low protein diets taken in by mother during pregnancy can impact foetal health and development e.g. protein affects number of neurones forming at time of conception
How does maternal medication have a lasting impact on foetal health?
Could cross placenta and be modified to affect child
Give an example of an environmental factor/exposure that could have a lasting impact on foetal health
Exposure to pesticides
What two types of influences on long term health of the foetus are there?
-
Biological (nature)
- Genetics
- Epigenetics
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Social and environmental (nurture)
- Environment
- Family, neighbourhood, school- including interactions child has with others
- Nutrition
- Social- substance use, care giver behaviour
- Health provisions and access to healthcare
What is the Barker hypothesis?
Early life influences can be predictors of health status in adulthood
How did the Barker study show that early life influences can be predictors of health status in adulthood?
- On average, adults who had a coronary event had been small at birth and thin at 2 years of age
- But after that they put on weight rapidly compared to their peers
- The risk of coronary events was more strongly related to the rate of change of childhood BMI, rather than to the BMI attained at any particular age of childhood
How can the Barker hypothesis be specifically applied to child health?
Under nutrition in utero and over nutrition as a child → increased risk of metabolic syndrome → leads to increased risk of cardiovascular events later in life
What is the mechanism of of the Barker hypothesis of increased risk of cardiovascular events later in life?
- The idea of programming in utero
- Leads to epigenetic changes which influence development and physiology
- If mother has malnutrition, then when foetus is born it has a high energy intake to catch up on nutrition missed during foetal development which leads to overshoot in nutrition which leads to cardiovascular problems as an adult
Explain this diagram
- Environment the foetus is in along with its nutritional supply, hormonal exposure (from mother) and vascular blood supply all affect gene expression in foetus
- If these alter gene expression, this will alter foetus in things like metabolism, immune responses etc
- When that foetus is born, it will experience other environmental changes e.g. smoking in adulthood
- These can manifest later in life as health disorders
What does the programming in utero involve?
These changes might include predictive adaptive responses (PARs)
What are PARs?
PARs are proposed to be developmental adaptations taken to prepare the fetus for its future environment
PARs don’t benefit the fetus immediately, but are taken in anticipation of the environment they will be exposed to.
How does a mis-match between PAR and actual environment contribute to disease risk later in life?
If a foetus acquires PARs in anticipation of a particular post-natal environment, but then encounters a different environment to that predicted, it will be mal-adapted, potentially raising the risk of ill-health in later life.
What diseases can we associate with early environmental exposures?
- Cardiovascular disease
- T2DM
- Lung disease
- Cancer risk
- Neurological, special sense and intellectual development
- Allergic and autoimmune diseases
How might environmental influences feed through to fetal physiology and programming?
Thought to be three major mechanisms:
- Hormonal effects (especially glucocorticoid exposure)
- Epigenetic modifications
- Irreversible developmental changes in organ size/structure
Explain the link between Glucocorticoid exposure & DOHaD
Fetal glucocorticoid exposure is usually regulated by placental 11BHSD2 enzyme
Reduction in 11BHSD2 expression or increased maternal GCs may lead to greater fetal GC exposure.
This, in turn, ‘programmes’ fetal growth, development and metabolism
(+ wider HPA axis dysregulation, changes in GC receptor expression)
Explain the link between DOHaD to biology: epigentic mechanisms
Epigenetic changes modify the expression of genes without modifying DNA sequence
Includes DNA methylation, post-translational (protein) modification of histones, and non- coding RNAs
In utero exposures can modify the types or levels of these epigenetic marks, leading to altered/dysregulated gene expression.
What does this diagram show?
Key windows of epigenetic reprogramming during development are points of vulnerability
What are some examples showing that environmental stimuli impact the development of key organ systems?
Fetal hypoxia -> reduced nephron numbers -> increased risk of hypertension/renal disease in adulthood
Fetal undernutrition -> reduced beta cell mass/altered muscle insulin sensitivity -> impaired glucose control in adulthood
What are the implications for later generations of in utero exposures?
- Primordial Germ Cells (PGCs) are the embryonic precursor cells of oocytes and spermatozoa
- PGCs undergo epigenetic reprogramming during embryogenesis
- These cells then give rise to sperm and egg – which transmit these epigenetic marks to the next generation (i.e. the exposed fetus’ offspring).
- Experimental data from animal models indicates that fetal germ cell development is sensitive to environmental impacts (eg diet, pharmaceuticals)
Summarise how the extrauterine environment can impact embryo and foetal development and health across the life-course.
