1b Early Environment and Biological Impacts on Health

Question 1

What challenges might the fetus face in utero (6)?

Answer 1

• fetal infection
• maternal nutrition
• maternal illness
• maternal stress
• maternal medication
• environmental factors/exposures

Question 2

What did the Barker Hypothesis conclude?

Answer 2

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

Question 3

What is DOHaD?

Answer 3

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

Question 4

What is epigenetics?

Answer 4

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)

Question 5

Describe the mechanism of the DOHaD

Answer 5

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

Question 6

Describe how the DOHaD mechanism links to biology?

Answer 6

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

Question 7

What are the benefits of the NHS Health Child Programme?

Answer 7

Universal
Reducing healthcare inequalities

Aims to prevent disease and promote good health

Question 8

What are the aims of the NHS Health Child Programme (6)?

Answer 8

Health promotion
Supporting care giving
Screening
Immunisation
Identification of high risk families
Signposting

Question 9

What are the fundamentals of a good screening test?

Answer 9

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

Question 10

What are three examples of Early Screening tests?

Answer 10

Newborn check
Newborn Hearing Screen
Blood Spot Check

Question 11

What is SureStart?

Answer 11

Aims to help and support families with under 5’s in low income households, parent and child education and health promotion

Question 12

Describe one screening test which is undertaken pre-conception?

Answer 12

T1DM/T2DM- diabetic eye test

Question 13

What is one screening tests which is done in the first trimester?

Answer 13

• Bloods for sickle cell and thalassaemia
• Blood for Hb, group, rhesus and antibodies

Question 14

What is one screening tests which is done in the second / third trimester of pregnancy?

Answer 14

Screening for down’s syndrome and fetal abnormalities = for the foetus

Question 15

Describe one screening tests which is undertaken in the new born period?

Answer 15

new born hearing screening

New born blood spot screening for MCADD, cystic fibrosis, PKU and congenital hypothyroidism and sickle cell disease

Question 16

What is fetal programming?

Answer 16

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

Question 17

What are PARs

Answer 17

• 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

Question 18

What happens if there is a mismatch between PARs and actual environment

Answer 18

• 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

Question 19

What things are early environmental exposures associated with (6)?

Answer 19

• Cardio-vascular disease
• Type 2 diabetes
• Lung disease
• Cancer risk
• Neurological, special sense and intellectual development
• Allergic and auto-immune diseases

Question 20

What challenges could the fetus face in utero that
might have lasting impact on its health (3)?

Answer 20

Thought to be three major mechanisms:
• Hormonal effects (especially glucocorticoid exposure)
• Epigenetic modifications
• Irreversible developmental changes in organ size structure

Question 21

What enzyme is fetal glucocorticoid exposure is usually regulated by?

Answer 21

placental 11BHSD2 enzyme

Question 22

What does reduction in 11BHSD2 expression or
increased maternal GCs lead to?

Answer 22

greater fetal GC exposure

Question 23

What does greater fetal GC exposure cause?

Answer 23

‘programmes’ fetal growth, development and metabolism

(+ wider HPA axis dysregulation, changes
in GC receptor expression)

Question 24

What are examples of epigenetic changes?

Answer 24

• DNA methylation
• post-translational (protein) modification of
  histones
• non- coding RNAs

Question 25

How do in utero exposures affect epigenetics?

Answer 25

In utero exposures can modify the types or levels of these epigenetic marks, leading to altered/dysregulated gene expression

Question 26

What are the three major windows of developmental vulnerability?

Answer 26

• Gametogenesis
• Early development
• Organogenesis and fetal growth

Question 27

What is important about gametogenesis?

Answer 27

parent-specific epigenetic marks are established during the development of sperm and oocytes

Question 28

What is important about Early development?

Answer 28

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.

Question 29

What is important about Organogenesis and fetal growth?

Answer 29

epigenetic marks influence timing and onset of
cell-type-specific gene expression, influencing how cells differentiate

Question 30

What are examples of environmental stimuli that have been shown to impact the development of key organ systems, pre-disposing to adult disease?

Answer 30

• Fetal hypoxia
• Fetal undernutrition

Question 31

How does Fetal hypoxia predispose to adult disease?

Answer 31

Fetal hypoxia -> reduced nephron
numbers -> increased risk of
hypertension/renal disease in adulthood

Question 32

How does Fetal undernutrition predispose to adult disease?

Answer 32

Fetal undernutrition -> reduced beta cell
mass/altered muscle insulin sensitivity -
> impaired glucose control in adulthood

Question 33

What are the embryonic precurur cells of oocytes and spermatozoa?

Answer 33

Primordial Germ Cells (PGCs)

Question 34

What happens to PGCs during embryogenisis?

Answer 34

They undergo epigenetic reprogramming.

These cells then give rise to sperm and egg –
which transmit these epigenetic marks to the
next generation

Question 35

What do experimental data from animal models indicate?

Answer 35

fetal germ cell development is sensitive to environmental impacts (eg diet, pharmaceuticals)