🐣Dev and Ageing🐣 - Early Environmental & Biological Impacts Flashcards
What challenges could the foetus face in utero that might have lasting impact on its health?
Foetal infection in utero
Maternal under/over nutrition
Maternal illness
Maternal stress
Maternal medication
Environmental factors/exposures
What did a study looking at childhood BMI and coronary events in adults?
The risk of coronary events (in later life) was more strongly related to the rate of change of childhood BMI, rather than to the BMI attained at any particular age of childhood
What is the connection with undernutrition, overnutrition, metabolic syndrome and cardiovascular events?
Undernutrition in utero and overnutrition as a child
Leads to
Increased risk of “metabolic syndrome” - in turn leads to increased risk of cardiovascular events
What is the idea of “programming” in utero?
Environmental factors during critical periods of foetal development (especially in utero) can permanently shape the structure, function, and metabolism of the body
These changes might include predictive adaptive responses (PARs)
What are predictive adaptive responses (PARs)?
proposed to be developmental adaptations taken to prepare the foetus for its future environment
PARs don’t benefit the foetus immediately, but are taken in anticipation of the environment they will be exposed to
Outline maternal malnutrition as an example of PARs
high energy intake leads to obesity
What are the potential negative impacts of PARs?
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
How are the mechanisms of DOHaD linked to biology and conditions in later life?
No need to memorise, but be able to explain the concept
What are the three major mechanisms that are thought to drive PARs?
Hormonal effects (especially glucocorticoid exposure)
Epigenetic modifications
Irreversible developmental changes in organ size/structure
What can lead to increased foetal glucocorticoid exposure?
Maternal stress, undernutrition, infections, or exogenous glucocorticoid treatments all raise maternal glucocorticoid levels
11βHSD2 expression is reduced or if maternal GCs are excessively high
What is 11βHSD2?
An enzyme in the placenta that converts active cortisol into its inactive form (cortisone), reducing foetal exposure
What is the effect of increased foetal GC load?
What are epigenetic mechanisms in the context of DOhaD?
Epigenetic mechanisms regulate gene expression without altering DNA sequences. These changes can be long-lasting and influence health.
What are the types of epigenetic mechanisms?
DNA methylation – Silences genes by adding methyl groups to DNA
Histone modifications – Alters how DNA is packed, changing gene accessibility
Non-coding RNAs – Regulate gene expression without making proteins
How do in utero exposures affect epigenetics?
Maternal stress, poor nutrition, or environmental toxins can modify foetal epigenetic marks, leading to:
Growth restriction
Altered metabolism
Increased fat storage
What are some examples of epigenetic in utero impacts on long term health?
Increased energy storage → Higher risk of obesity & diabetes
Fewer kidney cells → Higher risk of hypertension
Brain changes → Risk of stroke, schizophrenia, depression
What are key windows of epigenetic vulnerability?
Gametogenesis
Early development
Organogenesis and fetal growth
Outline gametogenesis as a key window of epigenetic vulnerability
Parent-specific epigenetic marks are established during the development of sperm and oocytes
Outline early development as a key window of epigenetic vulnerability
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
Outline organogenesis and foetal growth as a key window of epigenetic vulnerability
Epigenetic marks influence timing and onset of cell-type-specific gene expression, influencing how cells differentiate
Why are developmental stages epigenetically sensitive?
Each stage involves major rewiring of gene expression, making it susceptible to environmental disruptions
Changes made in early life persist long-term, potentially increasing risk of diseases in adulthood
This explains how early-life experiences can have lifelong health consequences (DOHaD concept)
Give two examples of environmental stimuli that have been directly linked to disease in adult life
Foetal hypoxia -> reduced nephron numbers -> increased risk of hypertension/renal disease in adulthood
Foetal undernutrition -> reduced beta cell mass/altered muscle insulin sensitivity -> impaired glucose control in adulthood
What are primordial germ cells (PGCs)?
Embryonic precursor cells of oocytes and spermatozoa
What is the link between PGC and epigenesis?
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 foetus’ offspring)
