Impact of the Environment on Lifelong Health Flashcards
What impacts on a fetus in utero can have a lasting impact?
- fetal infection
- maternal nutrition
- maternal illness
- maternal stress
- maternal medication
- environmental factors/exposures
What are the possible biological (nature) influences on long term health?
- genetics
- epigenetics
What are the possible social/environmental (nurture) influences on long term health?
- environment
- family/neighbourhood, school
- nutrition
- social (behaviours observed, substance use, care-giver behaviour)
- health provisions
What are the conclusions of the Barker hypothesis?
- adults that had a coronary event had been small at birth -> 2 yrs
- thereafter gained weight rapidly
- the risk of coronary events was more strongly related to the rate of change of childhood BMI, rather than BMI at a specific time.
What is the Barker/DOHaD hypothesis?
Undernutrition in utero and over nutrition as a child leads to an increased risk of ‘metabolic syndrome’ and therefore increased risk of CV events
What are the three major mechanisms for fetal reprogramming?
- hormonal effects (glucocorticoid exposure)
- epigentic modifications
- irreversible developmental changes in organ size/structure
What does DOHaD stand for?
Developmental Origins of Health and Disease
What is epigenetics?
heritable changes in DNA that do not change the nucleotide sequence but influence gene expression.
What are some epigenetic changes in the DNA?
- DNA methylation
- modification of histones post-translation
- non-coding RNA
What are the fetal epigenomic changes caused by maternal stress?
- fetal growth restriction
- obesity (increased energy storage)
- diabetes mellitus (altered metabolism)
- hypertension/cardiovascular disease (changes in number of cardio/vascular myocytes and nephrons)
- stroke, schizophrenia, cognitive dysfunction, depression and behavioural disorders (altered neurons and brain cells)
What are the three key windows of epigenetic reprogramming in a fetus?
- gametogenesis
- early development
- organogenesis and fetal growth
What can influence fetal gene expression?
- maternal health and environment
- fetal nutrient demand:supply
- endocrine mileu
- placental vascular supply
What are some fetal developmental responses to its altered gene expression?
- altered endocrinology and metabolism
- changes in fetal bone and lean and fat mass
- altered blood flow
- altered immune response
What is the mechanism of the developmental origin of health and disease?
- ‘programming’ in utero
- leads to epigenetic changes that influence development and physiology
- changes ay include predictive adaptive responses (PARS)
What are PARs?
- developmental adaptations taken to prepare the ftus for its future environment after birth
- don’t benefit the fetus immediately
What diseases are associated with early environmental exposures?
- CVD
- DMT2
- lung disease
- cancer risk
- allergic and autoimmune diseases
- neurological, special sense and intellectual development
What can cause increased fetal glucocorticoid exposure?
- increased maternal stress releasing more glucocorticoids
- decreased 11BHSD2 enzyme expression in placental
What is the effect of increased fetal glucocorticoid exposure?
- reprogramming of fetal growth, development and metabolism
- HPA axis dysregulation
- changes in GC receptor expression
- leads to adult disease
What are the effects of fetal hypoxia?
- reduced nephron numbers
- increased risk of hypertension and renal disease in adulthood
What are the effects of fetal undernutrition?
- reduced beta cell mass
- altered muscle insulin sensitivity
- impaired glucose control in adulthood
What are primordial germ cells?
Embryonic precursor cells of oocytes and spermatozoa
What happens to PGCs in embryogenesis?
- undergo epigenetic reprogramming
- gives rise to sperm and egg which transmit these epigenetic markers to the next generation
- sensitive to environmental impacts
