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frontiers in physiology > Transgenerational programming of disease > Flashcards

Transgenerational programming of disease Flashcards

1
Q

What us the definition of low birth weight?

A
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2
Q

What causes low birth weight in developed countries?

A

Placental insufficiency

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3
Q

What is the incidence of intrauterine growth restriction?

A

2 - 10% of babies

*This is 2 - 3 times normal perinatal mortality

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4
Q

What causes low birth weight in developing countries?

A

Maternal undernutrition

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5
Q

What are some other causes of babies being born small?

A

Maternal disease

Genetic disease

Being born small does not count if born prematurely.

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6
Q

What is a feature that is common among all IUGR babies?

A

Low nutrient delivery to the baby

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7
Q

What is fetal programming?

A

Babies born small have an increased risk of developing adult disease. This occurs because they develop adaptations to survive in the short term which causes problems in the long term.

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8
Q

Does obesity and exercise influence programmed conditions?

A

Fetal programming of adult disease is independent of exercise and level of obesity. (I.e it is a separate risk factor)

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9
Q

What conditions are adults born small at a higher risk of developing?

A

Diabetes and obesity

Osteoporosis

Cardiovascular disease and hypertension

Renal disease

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10
Q

What are the critical periods of a child’s development?

A

Pre-conception

Pre-implantation

Implantation and placental development

Organogenesis

Maximal fetal growth

Prepartum maturation

Birth

Suckling

Weaning

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11
Q

What percentage of small babies have accelerated growth in utero?

A

90% of small babies have some degree of accelerated growth during the first 6 months.

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12
Q

How is heart disease rates influenced by accelerated growth?

A

Accelerated growth is independently associated with an increased risk of heart disease.

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13
Q

What happens to milk quality after birth of a small baby? How can this be fixed?

A

Mothers milk loses quality because the nutrition matches the placental delivery of nutrients

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14
Q

Why do these conditions result from impaired development?

A

Reduced organ development causing deficits and later life dysfunction. (more prone to second hits)

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15
Q

What are the changes in the kidneys during adulthood in IUGR males?

A

Restricted males get low nephron numbers at 6 months.

Glomerular hypertrophy

Normal glomerular volume

Increase in Blood pressure by 6 weeks

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16
Q

What are the changes in the kidneys during adulthood in IUGR females?

A

No increase in blood pressure at 18 months.

Low nephron number

Glomerular hypertrophy at 18 months

Increase in plasma creatinine and renal insufficiency at 18 months.

*Girls were better protected

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17
Q

What effects did uteroplacental insufficiency have on male babies of the F1 generation?

A

Low birth weight

Bone defects

Decrease in beta cell mass

Glucose intolerance

Decrease in skeletal muscle mitochondrial biogenesis

Increase in BP and lower cardiomyocyte number

Lower nephron number and glomerular hypertrophy

Increased mesenteric vessel stiffness and less relaxation

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18
Q

What symptoms did F1 females develop?

A

Like males:

Low birth weight

Bone defects

Decrease in beta cell mass but didn’t develop glucose intolerance

Decrease in renal nephron number and glomerular hypertrophy.

Unlike Males:

Females did not experience skeletal muscle mitochondrial biogenesis.

Females did not experience higher Blood pressure

Females experienced glomerular hypertrophy at 18 months unlike males who developed it at 6 months

Unlike males females did not develop stiffness in their mesenteric vessels but rather they experienced stiffness in their uterine vessels

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19
Q

What is the general difference between how males and females react to IUGR?

A

Both males and females exhibit organ deficits but females are protected from the harsh effects of these organ defects.

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20
Q

What happens to the phenotype of small birth weight with age?

A

With age the phenotype gets worse. Several other phenotypes also make the condition worse.

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21
Q

What effect does exercise have on beta cell mass?

A

If exercise is done early in life it can increase beta cell number to full and reduce metabolic conditions.

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22
Q

What happens when babies are cross-fostered with other mothers of healthy babies?

A

Cross-fostering a baby with other mothers completely reduced all the organ deficits and prevented high blood pressure and metabolic dysfunction.

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23
Q

What happens when babies are cross-fostered with other mothers of healthy babies?

A

Cross-fostering a baby with other mothers completely reduced all the organ deficits and prevented high blood pressure and metabolic dysfunction.

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24
Q

What causes low birth weight in developed countries?

A

Placental insufficiency

How well did you know this?
1
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2
3
4
5
Perfectly
25
Q

What is the incidence of intrauterine growth restriction?

A

2 - 10% of babies

*This is 2 - 3 times normal perinatal mortality

26
Q

What causes low birth weight in developing countries?

A

Maternal undernutrition

27
Q

What are some other causes of babies being born small?

A

Maternal disease

Genetic disease

Being born small does not count if born prematurely.

28
Q

What is a feature that is common among all IUGR babies?

A

Low nutrient delivery to the baby

29
Q

What is fetal programming?

A

Babies born small have an increased risk of developing adult disease. This occurs because they develop adaptations to survive in the short term which causes problems in the long term.

30
Q

Does obesity and exercise influence programmed conditions?

A

Fetal programming of adult disease is independent of exercise and level of obesity. (I.e it is a separate risk factor)

31
Q

What conditions are adults born small at a higher risk of developing?

A

Diabetes and obesity

Osteoporosis

Cardiovascular disease and hypertension

Renal disease

32
Q

What are the critical periods of a child’s development?

A

Pre-conception

Pre-implantation

Implantation and placental development

Organogenesis

Maximal fetal growth

Prepartum maturation

Birth

Suckling

Weaning

33
Q

What percentage of small babies have accelerated growth in utero?

A

90% of small babies have some degree of accelerated growth during the first 6 months.

34
Q

How is heart disease rates influenced by accelerated growth?

A

Accelerated growth is independently associated with an increased risk of heart disease.

35
Q

What happens to milk quality after birth of a small baby? How can this be fixed?

A

Mothers milk loses quality because the nutrition matches the placental delivery of nutrients

36
Q

Why do these conditions result from impaired development?

A

Reduced organ development causing deficits and later life dysfunction. (more prone to second hits)

37
Q

What are the changes in the kidneys during adulthood in IUGR males?

A

Restricted males get low nephron numbers at 6 months.

Glomerular hypertrophy

Normal glomerular volume

Increase in Blood pressure by 6 weeks

38
Q

What are the changes in the kidneys during adulthood in IUGR females?

A

No increase in blood pressure at 18 months.

Low nephron number

Glomerular hypertrophy at 18 months

Increase in plasma creatinine and renal insufficiency at 18 months.

*Girls were better protected

39
Q

What conditions are transferred across the paternal line?

A

Paternal line programs glucose intolerance and reduced first phase insulin secretion.

Paternal line also increased relative wall thickness of the heart

Slowed growth was another seen effect in the F2 generation

40
Q

What symptoms did F1 females develop?

A

Like males:

Low birth weight

Bone defects

Decrease in beta cell mass but didn’t develop glucose intolerance

Decrease in renal nephron number and glomerular hypertrophy.

Unlike Males:

Females did not experience skeletal muscle mitochondrial biogenesis.

Females did not experience higher Blood pressure

Females experienced glomerular hypertrophy at 18 months unlike males who developed it at 6 months

Unlike males females did not develop stiffness in their mesenteric vessels but rather they experienced stiffness in their uterine vessels

41
Q

What is the general difference between how males and females react to IUGR?

A

Both males and females exhibit organ deficits but females are protected from the harsh effects of these organ defects.

42
Q

What happens to the phenotype of small birth weight with age?

A

With age the phenotype gets worse. Several other phenotypes also make the condition worse.

43
Q

What effect does exercise have on beta cell mass?

A

If exercise is done early in life it can increase beta cell number to full and reduce metabolic conditions.

44
Q

What effect does accelerated growth after birth have on the baby?

A

Early accelerated growth after birth can be protective and late accelerated growth is detrimental

45
Q

What happens when babies are cross-fostered with other mothers of healthy babies?

A

Cross-fostering a baby with other mothers completely reduced all the organ deficits and prevented high blood pressure and metabolic dysfunction.

46
Q

Summary

A

prenatal and postnatal nutritional environments and subsequent growth profiles are critical to define the adult disease pheneotype with sex-specific programming

47
Q

What have human epidemiological studies shown about the nature of transgenerational programming?

A

There is strong evidence for maternal line transmission.

Less evidence for father

48
Q

What is the greatest physiological challenge affecting females?

A

pregnancy

49
Q

True or False: Females born small never experience any harm from being born small

A

False, females born small exhibit problems during pregnancy.

I.e Pregnancy is a second hit

50
Q

What problems do pregnant f1 programmed females experience?

A

Glomerular hypertrophy and vascular adaptations

impaired glucose tolerance and future diabetes risk

51
Q

What happens to the F2 generation of small F1 generation females?

A

Smaller F2 fetuses

F2 pancreatic and nephron deficits

52
Q

Why do the F2 generation suffer from these deficits?

A

Adverse F1 pregnancy adaptations may impact on transgenerational disease transmission

53
Q

What is the effect of maternal stress on the offspring?

A

Maternal stress was associated with growth restriction and reduction in birth weight.

i.e maternal stress acts as a second hit

54
Q

What was the effect on nephron number in F2 generation?

A

F2 nephron number was reduced in F2 restricted males and females at E20 but this was restored after birth PN35,

55
Q

What happened to blood pressure of males of the F2 restricted rats?

A

High blood pressure was seen in males but not females

56
Q

Did the F2 generation experience the effects because of being born small themselves?

A

F2 generation was not born small. But they exhibited the effects of programming

57
Q

What happened to insulin secretion in F2 adult males born small?

A

First phase insulin secretion decreased and high blood pressure in the absense of maternal stress and growth defects.

58
Q

How do maternal stress and birth weight influence overall health?

A

Maternal stress and maternal birth weight have differential roles that contribute to the final offspring birth weight and metabolic and cardiorenal health, with both having the independent capacity to influence fetal growth and organ development later in life

59
Q

What is the result of obese pregnancy?

A

Gestational hypertension, diabetes, and preeclampsia

60
Q

What is the effect of high fat diet on glucose tolerance in females born small?

A

High fat diet exacerbated pre-existing glucose intolerance in females born small.

61
Q

What does exercise before and during pregnancy do to development and exacerbation of glucose intolerance?

A

Exercise before and during pregnancy prevents development and exacerbation of glucose tolerance

frontiers in physiology (35 decks)

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