Early Environmental and Biological Impacts on Lifelong Health

Question 1

Challenges in utero?

Answer 1

-fetal infection
-maternal nutrition
-maternal illness
-maternal stress
-maternal medication

Question 2

DOHaD?

Answer 2

Developmental origins of health and disease

on average, adults who had a coronary event had been small at birth and thin at two years of age

Question 3

Coronary event and childhood BMI correlation?

Answer 3

Risk of coronary events more strongly related to the rate of change of childhood BMI, rather than to the BMI attained at any particular age

Question 4

DOHaD hypothesis?

Answer 4

Under nutrition in utero or over nutrition as a child has an increased risk of metabolic syndrome which leads to increased risk of cardiovascular events

Question 5

DOHaD mechanisms?

Answer 5

Idea of programming in utero leads to changes which influence development and physiology
Might include predictive adaptive responses

Question 6

PARs?

Answer 6

PREDICTIVE ADAPTIVE RESPONSES

Developmental adaptations taken to prepare foetus for future environment

Don’t benefit foetus immediately but taken in anticipation for future environment

Question 7

Mismatch between PAR and actual environment?

Answer 7

Increases risk of disease from unpredicted excess

Question 8

Factors that affect foetal developmental responses?

Answer 8

Maternal health and environment
Foetal nutrient demand
Endocrine
Placental vascular supply

Question 9

What conditions are early environmental exposures linked to?

Answer 9

CVD
T2DM
Lung disease
Cancer
Neurological conditions
Allergic and autoimmune conditions

Question 10

Three major mechanisms in utero that have a lasting impact on health?

Answer 10

1. Hormonal effects (especially glucocorticoid exposure)
2. Epigenetic modifications
3. Irreversible developmental changes in organ size/structure

Question 11

What is fetal glucocorticoid exposure regulated by?

Answer 11

Placental 11BHSD2 enzyme

Question 12

What can cause greater fetal glucocorticoid exposure?

Answer 12

Decreased 11BHSD2 expression
Increased maternal GCs

Question 13

What does fetal GC exposure do?

Answer 13

Programmes fetal growth, development and metabolism
Wider HPA axis dysregulation

Question 14

Epigenetic changes?

Answer 14

Modify expression of genes without modifying DNA sequence
Includes DNA methylation, post-translational (protein) modification of histones, non-coding RNAs

Question 15

Three key windows of Epigenetic reprogramming?

Answer 15

Are points of vulnerability:
Gametogenesis
Early development
Organogenesis and foetal growth

Question 16

Gametogenesis epigenetics?

Answer 16

Parent-specific Epigenetic marks are established during development of sperm and oocytes

Question 17

Early development epigenetics?

Answer 17

Very early embryos undergo widespread erasure and re-patterning of Epigenetic marks during which these gamete-specific marks are erased and new Epigenetic profiles are established

Question 18

Organogenesis and foetal growth epigenetics?

Answer 18

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

Question 19

Fetal hypoxia effect?

Answer 19

Leads to reduced nephron numbers -> increased risk of hypertension renal disease in adulthood

Question 20

Fetal undernutrition effect?

Answer 20

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

Question 21

Primordial germ cells?

Answer 21

Embryonic precursor cells of oocytes and spermatozoa
Undergo Epigenetic reprogramming during embryogenesis
Give rise to sperm and egg, which transmit these Epigenetic marks to next generation

Question 22

Epigenetic reprogramming during embryogenesis leads to?

Answer 22

Trans generational effects (can affect grandchildren)