1b Early Environment and Biological Impacts on Health Flashcards
What challenges might the fetus face in utero?
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?
Epigenetic changes modify the expression of genes without modifying DNA sequence
Includes DNA methylation, post-translational (protein) modification of histones, and non- coding RNAs
Describe the mechanism of the DOHaD
PARs (predictive adaptive responses) 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.
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 mal-adapted, potentially raising the risk of ill-health in later life.
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 eb amplified during infancy, and then adding adult behaviours -> leads to increased risk of CVD incidents
What challenges could the fetus face in utero that might have lasting impact on its health?
Hormonal effects (especially glucocorticoid exposure)
Epigenetic modifications
Irreversible developmental changes in organ size/structure
What is fetal programming?
Fetal programming, or prenatal programming, isa 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 is fetal glucocorticoid exposure regulated by?
Placental 11BHSD2 enzyme
What might a reduction in 11BHSD expression or increased maternal GC lead to?
Greater fetal GC exposure.
Programmes fetal growth, development and metabolism
Wider HPA axis dysregulation, changed in GC receptor expression
What changes does increased exposure to GC cause?
Changes in
Growth
Organ structure
Cell numbers
Gene expression
Neuro/endocrinal function
Metabolism
How can fetal epigenomic changes lead to health conditions?
Fetal growth restriction
Increased capacoty to store energy - Obesity
Adaptations in metabolic pathways - diabetes mellitus
Adaptationds in terminally diffrentiated cell numbers can lead to htn, cvd, stroke, schizophrenia
What are the three major windows of developmental vulnerability?
Gametogenesis: parent-specific epigenetic marks are established during the development of sperm and oocytes
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.
Organogenesis and fetal growth: epigenetic marks influence timing and onset of cell-type-specific gene expression, influencing how cells differentiate
In which ways can environmental stimuli impant the development of key organ systems, pre-disposing to adult disease?
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 PGCs?
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).
