1b Early Environment and Biological Impacts on Health Flashcards
What challenges might the fetus face in utero (6)?
- fetal infection
- maternal nutrition
- maternal illness
- maternal stress
- maternal medication
- environmental factors/exposures
What did the Barker Hypothesis conclude?
DOHaD Hypothesis:
Undernutrition in utero
Followed by overnutrition as a child
Lead to increased risk of Metabolic Syndrome which in turns leads to increased risk of CVD events
What is DOHaD?
Developmental Origins of Health and Disease - a concept where environmental insults in early life can contribute to long-term risk of NCDs and an individual’s short- and long-term health
What is epigenetics?
heritable changes in marks on the DNA which do not effect the nucleotide sequences but influence how genes are expressed (where, when and how much a gene is switched off)
Describe the mechanism of the DOHaD
Maternal malnutrition - the baby is born underweight, therefore has a higher energy intake (to compensate for the lack of nutrition - this puts the baby at risk of an OVERSHOOT), so is more likely to have a high BMI, and puts the baby at risk of metabolic syndrome, or CVD
Describe how the DOHaD mechanism links to biology?
Foetal genes have particular sequences -> these are switch on and off during stages of development
Things like the uterine environment, nutritional supply, vascular blood supply (pre-eclampsia) -> these environmental impacts have an impact on gene expression.
When born, we are exposed to another set of environmental stimuli -> there impacts might be amplified during infancy, and then adding adult behaviours -> leads to increased risk of CVD incidents
What are the benefits of the NHS Health Child Programme?
Universal
Reducing healthcare inequalities
Aims to prevent disease and promote good health
What are the aims of the NHS Health Child Programme (6)?
Health promotion
Supporting care giving
Screening
Immunisation
Identification of high risk families
Signposting
What are the fundamentals of a good screening test?
Have to be able to be identified before a critical point, treatable and prevent/reduce morbidity
Acceptable and eay to administer
Cost effective
Provide Accurate Results
What are three examples of Early Screening tests?
Newborn check
Newborn Hearing Screen
Blood Spot Check
What is SureStart?
Aims to help and support families with under 5’s in low income households, parent and child education and health promotion
Describe one screening test which is undertaken pre-conception?
T1DM/T2DM- diabetic eye test
What is one screening tests which is done in the first trimester?
- Bloods for sickle cell and thalassaemia
- Blood for Hb, group, rhesus and antibodies
What is one screening tests which is done in the second / third trimester of pregnancy?
Screening for down’s syndrome and fetal abnormalities = for the foetus
Describe one screening tests which is undertaken in the new born period?
new born hearing screening
New born blood spot screening for MCADD, cystic fibrosis, PKU and congenital hypothyroidism and sickle cell disease
What is fetal programming?
Fetal programming, or prenatal programming, is a concept that suggests certain events occurring during critical points of pregnancy may cause permanent effects on the fetus and the infant long after birth
What are PARs
- predictive adaptive responses (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
What happens if there is a mismatch between PARs and actual environment
- contributes to disease risk later in life
- If a fetus acquires PARs in anticipation of a particular post-natal environment, but then encounters a different environment to that predicted, it will be maladapted, potentially raising the risk of ill-health in later life
What things are early environmental exposures associated with (6)?
• Cardio-vascular disease
• Type 2 diabetes
• Lung disease
• Cancer risk
• Neurological, special sense and intellectual development
• Allergic and auto-immune diseases
What challenges could the fetus face in utero that
might have lasting impact on its health (3)?
Thought to be three major mechanisms:
• Hormonal effects (especially glucocorticoid exposure)
• Epigenetic modifications
• Irreversible developmental changes in organ size structure
What enzyme is fetal glucocorticoid exposure is usually regulated by?
placental 11BHSD2 enzyme
What does reduction in 11BHSD2 expression or
increased maternal GCs lead to?
greater fetal GC exposure
What does greater fetal GC exposure cause?
‘programmes’ fetal growth, development and metabolism
(+ wider HPA axis dysregulation, changes
in GC receptor expression)
What are examples of epigenetic changes?
- DNA methylation
- post-translational (protein) modification of
histones - non- coding RNAs
How do in utero exposures affect epigenetics?
In utero exposures can modify the types or levels of these epigenetic marks, leading to altered/dysregulated gene expression
What are the three major windows of developmental vulnerability?
• Gametogenesis
• Early development
• Organogenesis and fetal growth
What is important about gametogenesis?
parent-specific epigenetic marks are established during the development of sperm and oocytes
What is important about Early development?
very early embryos undergo widespread erasure and re-patterning of epigenetic marks during which these gamete-specific marks are erased and new epigenetic profiles established.
What is important about Organogenesis and fetal growth?
epigenetic marks influence timing and onset of
cell-type-specific gene expression, influencing how cells differentiate
What are examples of environmental stimuli that have been shown to impact the development of key organ systems, pre-disposing to adult disease?
- Fetal hypoxia
- Fetal undernutrition
How does Fetal hypoxia predispose to adult disease?
Fetal hypoxia -> reduced nephron
numbers -> increased risk of
hypertension/renal disease in adulthood
How does Fetal undernutrition predispose to adult disease?
Fetal undernutrition -> reduced beta cell
mass/altered muscle insulin sensitivity -
> impaired glucose control in adulthood
What are the embryonic precurur cells of oocytes and spermatozoa?
Primordial Germ Cells (PGCs)
What happens to PGCs during embryogenisis?
They undergo epigenetic reprogramming.
These cells then give rise to sperm and egg –
which transmit these epigenetic marks to the
next generation
What do experimental data from animal models indicate?
fetal germ cell development is sensitive to environmental impacts (eg diet, pharmaceuticals)
