Theme C lecture 8 Flashcards
What is bilateral uterine vessel ligation?
A procendure used to decrease blood supply to fetus. It is a procedure designed to mimic uteroplacental insufficiency
What does bilateral uterine vessel ligation do in rats?
It causes a decrease in fetal nutrition in rats by means of uteroplacental insufficiency
What are the steps that lead to adult disease that are caused by uteroplacental insufficiency?
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.
Why is low birth weight such a problem?
It causes deficit in organ size.
Beta cell deficit
Nephron number deficit
Cardiomyocyte deficit
Why is low birth weight a problem for males but not females?
Females are protecte
Why is age considered a second hit?
Age is considered a second hit to a small fetus because effects caused by small birth weight worsen with age
How can conditions be prevented?
Conditions can be prevented by cross-fostering early fetuses.
Exercise from early age could diminish adult disease consequences.
What factors are important when defining adult disease phenotype?
Prenatal and postnatal nutrition environments and subsequent growth profiles are critical in defining adult disease phenotype with sex-specific programming.
What is transgenerational programming?
Pregnant females could then show characteristics which then can cause problems in the next generation
What are the normal adaptations to pregnancy?
Increase plasma volume + CO
Increase GFR
Increase insulin synthesis and secretion, insulin resistance
Decrease in peripheral, uterine and renal vascular resistance.
What are the problems that arise during pregnancy for women who are born small?
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.
What was the result of a mother born small being mated with normal males? (F1 generation)
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
What was the result of a mother born small being mated with normal males? (F1 generation during pregnancy)
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.
What was the result of a mother born small being mated with normal males? (F2 generation)
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.
Is the F2 generation programming caused by slowed growth?
No, Transgenerational programming ignores the low birth weight of the F2 generation.
What does maternal stress do to F2 generation and F1 mothers born small?
If the mother was stressed during gestation the F2 experienced low birth weight.
What is obesity a risk factor for in pregnant women?
Gestational hypertension, diabetes, and preeclampsia
What percentage of Australian pregnant women are overweight?
34%
What effect does a high fat diet have on glucose tolerance and how can this effect be reversed.
High fat diet exacerbates glucose intolerance in mothers born small.
This effect can be reversed by exercise.
What is the effect of increasing exercise during pregnancy?
Exercise prevented glucose intolerance by increasing beta cell mass
What happens to nephron number in the F2 generation mothers fed a high fat diet that are born small exercise during pregnancy?
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
What effect does obesity during pregnancy have on nephron number?
Obesity during pregnancy programs glucose intolerance and in turn low nephron number.
What happens to glucose control if father is born small?
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.
What happens to blood pressure if father is born small?
Males born to growth restricted fathers have high blood pressure by telemetry.
What happens to creatine clearance in restricted males?
It decreases
What happened the heart of F2 males 16 months of age?
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!
What phenotype is seen in F2 offspring of growth restricted mothers and father?
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.
What is the effect of stress on transgenerational disease programming?
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.
