early environment and biological impacts on lifelong health

Question 1

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

Answer 1

Fetal infection in utero

Maternal nutrition (under/over), illness, stress, medication

Environmental factors/exposures

Question 2

what does DOHaD stand for//what it is

Answer 2

developmental origins of health and disease hypothesis= programming adult health in early life

Question 3

DOHaD- conclusion that was made about risk of coronary events

Answer 3

coronary events risk= childhood BMI rate change, rather than BMI attained at any childhood age.

BMI change- small at birth and young. Then put weight on rapidly

Question 4

DOHaD- what does Undernutrition in utero and Overnutrition as a child lead to

Answer 4

increased risk of metabolic syndrome -> increase risk of cardiovascular events

Question 5

what is metabolic syndrome

Answer 5

Metabolic syndrome is a combination of health conditions such as obesity, high blood pressure, high blood sugar, and abnormal cholesterol levels that significantly increase the risk of cardiovascular disease and type 2 diabetes.

Answer 6

.

Question 7

what is PARs

Answer 7

predictive adaptive response

PARs are developmental adaptations in fetuses, to prepare it for future environments

ie. adequate nutrition=fine
maternal malnutrition-small baby-> baby with high energy intake= obesity in adulthood

Question 8

what does a A mis-match between PAR and actual environment mean

Answer 8

fetus maladapted + contribute to disease risk later in life.

Question 9

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

Answer 9

Hormonal effects (especially glucocorticoid exposure)

Epigenetic modifications

Irreversible developmental changes in organ size/structure

Question 10

Glucocorticoid exposure & DOHaD

Answer 10

1. maternal stress

2.Reduction in 11BHSD2 expression or increased maternal GCs may lead to greater fetal GC exposure.

3.fetal changes- wider HPA axis dysregulation// growth, cell number, metabolism etc

4. adult disease

Question 11

what does 11B-HSD2 stand for

Answer 11

11beta Hydroxysteroid Dehydrogenase 2

Question 12

Linking DOHaD to biology: epigenetic mechanisms::

Answer 12

1. maternal stress
   2.fetal epigenomic change
   3.a) fetal growth restriction
2. b increase capacity to store energy - obesity
   3.c) adaptation in metabolic pathways- DM
   3d) adaptation in terminally differentiated cells numbers-» heart=hypertension// brain=stroke

Question 13

what are epigenetic changes

Answer 13

modify the expression of genes without modifying DNA sequence

inc DNA methylation,
post-translational (protein) modification of histones, and
non- coding RNAs

Question 14

Key windows of epigenetic reprogramming during development are points of vulnerability

Answer 14

-gametogenesis (maternal + paternal environment)

-early dev- erasure of gametic identity and new epigenetic profile established.

-organogensis/foetal growth
epigenetic mark influence timing and onset of cell-type-specific gene expression + how cells develop

Question 15

DOHaD and in utero programming of organ systems? Fetal hypoxia vs fetal undernutrition

Answer 15

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

Question 16

what are PGCs

Answer 16

Primordial Germ Cells (PGCs)
=embryonic precursor cells of oocytes and spermatozoa

Question 17

what does PGC do during embryogenesis

Answer 17

epigenetic reprogramming

->PGC then give rise to sperm and egg – which transmit these epigenetic marks to the next generation

Question 18

what are PGC sensitive to and what it does

Answer 18

sensitive to environmental impacts (ie. diet/pharmaceutical)

high fat= reduces number of oocytes