Theme C lecture 8

Question 1

What is bilateral uterine vessel ligation?

Answer 1

A procendure used to decrease blood supply to fetus. It is a procedure designed to mimic uteroplacental insufficiency

Question 2

What does bilateral uterine vessel ligation do in rats?

Answer 2

It causes a decrease in fetal nutrition in rats by means of uteroplacental insufficiency

Question 3

What are the steps that lead to adult disease that are caused by uteroplacental insufficiency?

Answer 3

Uteroplacental insufficiency causes a decrease in mammary development and fetal growth.

Decreased mammary development causes a decrease in lactation.

Decreased lactation and fetal growth restriction together cause postnatal growth restriction and so as an adult the fetus experiences disease.

Question 4

Why is low birth weight such a problem?

Answer 4

It causes deficit in organ size.

Beta cell deficit

Nephron number deficit

Cardiomyocyte deficit

Question 5

Why is low birth weight a problem for males but not females?

Answer 5

Females are protecte

Question 6

Why is age considered a second hit?

Answer 6

Age is considered a second hit to a small fetus because effects caused by small birth weight worsen with age

Question 7

How can conditions be prevented?

Answer 7

Conditions can be prevented by cross-fostering early fetuses.

Exercise from early age could diminish adult disease consequences.

Question 8

What factors are important when defining adult disease phenotype?

Answer 8

Prenatal and postnatal nutrition environments and subsequent growth profiles are critical in defining adult disease phenotype with sex-specific programming.

Question 9

What is transgenerational programming?

Answer 9

Pregnant females could then show characteristics which then can cause problems in the next generation

Question 10

What are the normal adaptations to pregnancy?

Answer 10

Increase plasma volume + CO

Increase GFR

Increase insulin synthesis and secretion, insulin resistance

Decrease in peripheral, uterine and renal vascular resistance.

Question 11

What are the problems that arise during pregnancy for women who are born small?

Answer 11

Women born small are at risk of developing hypertension, glucose intolerance, and gestational diabetes in pregnancy.

This in turn causes low offspring birth weight leading to transgenerational development of F2 diseases.

Question 12

What was the result of a mother born small being mated with normal males? (F1 generation)

Answer 12

F1 females had the same body weight as the control F1 females and were not obese.

They had the same uterine and ovarian weights as the control F1 females

They had the same maternal blood pressure as the control F1 females

They had the same uterine vascular function as the control F1 females.

These results showed that these factors were not the cause of the problem

Question 13

What was the result of a mother born small being mated with normal males? (F1 generation during pregnancy)

Answer 13

Impaired glucose tolerance. This can impact fetal development.

Maternal kidneys experienced a nephron deficit and in turn glomerular hypertrophy and decrease in sodium excretion.

This procedure prevented blood pressure from decreasing too much and so normal BP was maintained in the short term.

Question 14

What was the result of a mother born small being mated with normal males? (F2 generation)

Answer 14

Gestational diabetes and other problems of growth restricted mothers has an impact on the next generation.

F2 nephron number was reduced by 15 - 22%. initially but this was reversed later on in development. (delayed nephrogenesis) This means development didn’t happen in a timely manner which could have bad impact in the future.

BP in boys was higher than the control at 6 - 9 months.

There was a decrease in F2 first phase insulin secretion in F2 6 month old males and females born to growth restricted mothers but normal glucose tolerance and insulin sensitivity.

There was a decrease in beta cell mass in males

There was an increase in beta-cell mass in females.

Question 15

Is the F2 generation programming caused by slowed growth?

Answer 15

No, Transgenerational programming ignores the low birth weight of the F2 generation.

Question 16

What does maternal stress do to F2 generation and F1 mothers born small?

Answer 16

If the mother was stressed during gestation the F2 experienced low birth weight.

Question 17

What is obesity a risk factor for in pregnant women?

Answer 17

Gestational hypertension, diabetes, and preeclampsia

Question 18

What percentage of Australian pregnant women are overweight?

Answer 18

34%

Question 19

What effect does a high fat diet have on glucose tolerance and how can this effect be reversed.

Answer 19

High fat diet exacerbates glucose intolerance in mothers born small.

This effect can be reversed by exercise.

Question 20

What is the effect of increasing exercise during pregnancy?

Answer 20

Exercise prevented glucose intolerance by increasing beta cell mass

Question 21

What happens to nephron number in the F2 generation mothers fed a high fat diet that are born small exercise during pregnancy?

Answer 21

Consumption of a high fat diet in mothers born of normal birth weight decreases male fetal nephron number.

Exercise in both mothers born small and of normal birth weight fed a high fat diet increase male F2 fetal nephron number compared to sedentary individuals

This shows that exercise reverses the effect of a high fat diet on nephron number

Question 22

What effect does obesity during pregnancy have on nephron number?

Answer 22

Obesity during pregnancy programs glucose intolerance and in turn low nephron number.

Question 23

What happens to glucose control if father is born small?

Answer 23

If father was born small son has 20% higher glucose compared to the control.

No changes were seen to insulin. But 50% reduction in first phase insulin secretion.

Question 24

What happens to blood pressure if father is born small?

Answer 24

Males born to growth restricted fathers have high blood pressure by telemetry.

Question 25

What happens to creatine clearance in restricted males?

Answer 25

It decreases

Question 26

What happened the heart of F2 males 16 months of age?

Answer 26

Increase was seen in left ventricular wall mass.

There were no changes to Left Ventricular Mass and contractility. This indicates there was concentric remodelling.

Heart changes in response to programming the father gave them!

Question 27

What phenotype is seen in F2 offspring of growth restricted mothers and father?

Answer 27

F2 offspring born to growth restricted mother and fathers have cardio-renal and metabolic phenotype with normal F2 birth weight.

*F1 mothers and F2 susceptible to adverse lifestyle changes.

Question 28

What is the effect of stress on transgenerational disease programming?

Answer 28

Stress acts as a second hit.

There are often many organ specific deficits take place

Adverse effects of a maternal High Fat Diet are improved with exercise preventing nephron deficits

Paternal line F2 transgenerational disease transmission is uniquely identified.