L11.2 Second hits

Question 1

What are the second hits?

Answer 1

• Gender → males greater risk than females
• Improving Diet/Lifestyle → may prevent/improve disease
• Age → older = ↑risk
• Pregnancy → increased susceptibility to pregnancy adaptations which may influence next generation

Question 2

Transgenerational Programming

Answer 2

• Not limited to affect the first generation
• Maternal line transmission

Question 3

Pregnancy adaptations for SGA mothers:

Answer 3

• SGA F1 pregnant females had impaired glucose tolerance
  
  • No difference in non-pregnant intraperitoneal glucose tolerance and insulin response test
    
    • No metabolic dysfunction
• Renal adaptations → to Preserves renal function and BP post pregnancy (but unsure what long-term effect may be)
  
  • ↓nephron deficit
  • ↑glomerular hypertrophy
  • ↓maternal Ma excretion
  • Normal BP

Question 4

Generations effects on F2 from SGA mothers

Answer 4

• Absence of low birth weight
• Delayed nephrogenesis → may have impact later on in life
• ↑BP in males (exacerbated in F2 compared to F1)
  
  • Unaffected in females
• ↓First phase insulin secretion in males and females
  
  • But ↓b-cell mass in males and ↑b-cell mass in females → may be protective
• Normal glucose tolerance and insulin sensitivity

Question 5

Stess from handling rats

Answer 5

• Maternal stress from handling rats
• Exacerbates F2 phenotype
  
  • Like a third hit

Question 6

Risk of obesity

Answer 6

• Obese women → ↑risk of gestational HT, diabetes, preeclampsia

Question 7

Result of maternal F1 high fat diet

Answer 7

• ↑body weight, ↑Dorsal fat deposited
• Exacerbates glucose intolerance
  
  • (Mother born small and pregnant develop glucose intolerance)

Question 8

Effect of exercise

Answer 8

• Prevents glucose intolerance by improving B-cell mass
• Increase nephron number
• Improves obesity

Question 9

What happens to F2 when dad is born small

Answer 9

transgenic due to post-natal growth/epigenetic programming; altered phenotype only seen in male F2

• Normal birthweight
• ↓50% first phase insulin
• Glucose intolerance → ↑20% glucose (may be from ↓b-cell mass or↓insulin)
• High BP
• Renal dysfunction → ↓creatinine clearnace
• ↑LVWT; no change in LVM and contractility
  
  • Concentric remodelling

Question 10

Smmary of F2 effect from SGA moms

Answer 10

Maternal line → trasngenic due to adverse pregnancy

• Normal birthweight
• Decrease 1st phase insulin secretion BUT NORMAL glucose tolerance
• ↑BP in males and NOT females
• ↓Nephron number
• NO CHANGES in cardiac parameters