Lecture 8: DOHAD: Second Hits & Transgenerational Programming

Question 1

What happens to boys and girls exposed to uteroplacental insufficiency?

Answer 1

Beta cell, nephron and cardiomyocyte deficit but boys have glucose intolerance, high BP, early life glomerular hypertrophy, vascular dysfunction and reduced skeletal muscle

Question 2

What are growth restricted female offspring not affected by?

Answer 2

CVD and metabolic disease

Question 3

What is the strong evidence for maternal line transmission?

Answer 3

Mother born small increased disease risk in children as opposed to if the father is born small

Question 4

What are the normal adaptations to pregnancy?

Answer 4

• Increased plasma volume and cardiac output
• Increased glomerular filtration rate
• Increased insulin synthesis and secretion, insulin resistance
• Decreased peripheral, renal and uterine vascular resistance

Question 5

What are women born small at risk of developing?

Answer 5

Hypertension, glucose intolerance and gestational diabetes in pregnancy

Question 6

What are the changes in nephron deficit, glomerular hypertrophy, sodium excretion and BP in growth restricted females during pregnancy?

Answer 6

• 33% decrease in nephron deficit
• 37% increase in glomerular hypertrophy
• 45% reduction in maternal sodium excretion
• Normal blood pressure

Question 7

What happens to females born small when they get pregnant?

Answer 7

Glomerular hypertrophy and vascular adaptations, impaired glucose tolerance and future diabetes risk

Question 8

In offspring of normal weight with mothers born small, what were the changes in nephron number?

Answer 8

Nephron number reduced (15-22%) in males and females whose mothers were born small at embryonic week 20, but restored to normal levels at week 35 - nephrogenesis is delayed (development didn’t happen at normal time - could have effect later in life

Question 9

How did BP change in offspring with mothers born small?

Answer 9

Males increased BP by 19mmHg - no change in females

Question 10

How did insulin levels and regulation change in offspring with mothers born small?

Answer 10

1st phase insulin secretion decreased in males and females but there was normal glucose tolerance and insulin sensitivity

Question 11

How did beta cell mass change in offspring with mothers born small?

Answer 11

Reduced in males, increased in females

Question 12

What happened to offspring if mother was stressed during pregnancy?

Answer 12

Lowered birth weight, glucose intolerance, LV hypertrophy and renal dysfunction

Question 13

What are the relationships between obesity and pregnancy?

Answer 13

• 34% of pregnant Australian women are obese
• Increased risk for gestational hypertension, diabetes and preeclampsia
• Individuals born small are predisposed to developing obesity

Question 14

On a high fat diet how did dorsal fat levels change and how were they reduced?

Answer 14

Increased with high fat diet, and exercise with high fat diet reduced dorsal fat from sedentary

Question 15

How does exercise reduce glucose intolerance?

Answer 15

Increases beta cell mass

Question 16

What effect did high fat diet have on nephron number?

Answer 16

Decreased foetal nephron number and exercise increased number

Question 17

What were the characteristics of males born to a growth restricted father?

Answer 17

20% increase in glucose 
No change in insulin
50% decrease in 1st phase insulin
Reduced beta cell mass
High BP
Reduced creatine clearance
11% increase in LV wall thickness
No change in contractility
Concentric heart remodelling