Early environment/biological impacts of health Flashcards
Issues in utero that can affect fetal development
Fetal Infection,
Maternal Nutrition/Illness/Stress/Medication,
Environment Exposure e.g. pesticides
What is the DOHaD Hypothesis?
Developmental Origins of Health and Disease Hypothesis - whether early exposures have major impacts in later life health. May pre-dispose certain health trajectories
Underlying concept behind the DOHad hypothesis (Barker study)
Undernutrition in utero + overnutrition in childhood -> to an ^ risk of metabolic syndrome -> ^ risk of cardiovascular events
What are the elements of metabolic syndrome?
T2DM, Hypertension, Obesity
What is fetal programming
Environmental stimuli experienced in the womb prepares fetus for later life conditions. Causes a series of epigenetic/physiological changes.
What are predictive adaptive responses - PAR
Developmental changes which are anticipatory of future conditions. E.g. if mother is malnourished, this may cause the child physiology to be one that adapts well to a low nutrient environment
Link between PAR and risk of disease in later life
Mismatch btw the expected environment and the actual environment encountered can cause the fetus to be maladapted. PAR not helpful and may cause increased risk of disease in later life
What link was found between BMI and risk of coronary events?
Risk of coronary event with high rate of change of childhood BMI. e.g. born small and rapidly gain weight leading to overshoot.
What is the biological mechanism of DOHaD?
Foetal gene expression is altered by maternal environment and nutrient supply - leads to developmental responses to do with metabolism, fat mass, blood flow and immune responses. This is amplified in infancy, leading to disease formation
What diseases have been found linked to DOHaD?
CVD, T2DM, Lung Disease, Cancer, Intellectual Development, Autoimmune, Allergy
3 Mechanisms of fetal programming
- Hormonal effects (overexposure to glucocorticoids)
- Epigenetic modifications
- Irreversible developmental changes in organ size/structure
What are epigenetic changes?
Heritable changes in DNA that modify gene expression w/o modifying DNA sq
What enzyme regulates fetal glucocorticoid exposure
Placental 11BHSD2, breaks down cortisol
What factors lead to increased fetal glucocorticoid exposure
Red 11BHSD2 expression
Increased maternal release of glucocorticoids/hormones due to stress
What is caused by increased fetal glucocorticoid (GC) load
Increased growth, metabolism, development (organ structure/ cell proliferation)
wider HPA axis dysregulation
changes in GC receptor expression
