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Samenvatting - Early Life Events (BMW33517)

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Samenvatting hoorcolleges Early life events BMW UU

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  • November 1, 2023
  • 24
  • 2022/2023
  • Summary
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Early life events

HC1: DOHAD: Developmental origins of Health and Disease

Developmental programming is the foetal or neonatal response to a specific challenge during a
critical developmental time window that alters organ development with resulting effects on offspring
function and health that can persist through life.

Challenges that result in programming are e.g.: maternal under- and overnutrition, paternal under
or over nutrition, environmental pollution and stress

IUGR: Intrauterine growth restriction kan voorkomen door genetische, placentele, foetale en
maternale factoren.




Short term effect of Fetal Growth Restriction (FGR)

1. Pulmonaire hypertensie

2. Hypothermia

3. Fetal death

4. Low serum feritinin

5. Immunodeficiency

6. Renal dysfunction

Long term effect of Fetal Growth Restriction (FGR)

7. Lage cognitieve scores

8. Growth retardation

9. Lage intiligentie

,10. Lage sociale competentie



Diermodellen:

11. Placental insufficiency and maternal undernutrition leidt tot kleinere baby

12. Maternal overnutrition leidt tot kleinere/normale baby

13. Maternal obesity leidt tot kleine/normale baby

14. Maternal diabetes leid tot grotere baby

Moeilijk om een conclusie te trekken uit dierlijke trials aangezien:

15. Verschillende dieren gebruikt zijn

16. Verschillende soorten zijn

17. Verschillende leeftijdscategorieën

18. Verschillende human cohorts met verschillende eigenschappen

FGR animal models

19. Dahl SS

20. RUPP

21. Protein/diet restricted

22. L-NAME treated

23. sFlt1-overexpression

24. Clamped umbilical cord

25. Clamped utero-overian arteries

26. Embolization of the uterine arteries with polystyrene microspheres (sheep; bigger animal)

27. COMT -/-

28. eNOS +/-

29. IGF2 -/-

30. LPS

31. Hypoxic chambers

FGR results in bloodpressure increase of ~10 mmHg in dierstudies:

32. Mannen vooral effect

33. Toename met leeftijd

34. Early-onset FGR results in more severe hypertension

No BP difference in human studies

, 35. Too much heterogeneity?

36. Less severe FGR?

37. Prematurity bigger influencer than FGR itself?

Sildenafil: PDE5 remmer – working mechanism




Sildenafil verbetert het geboortegewicht in een aantal diermodellen voor FGR. Prenatal sildenafil
dampens blood pressure progression and improves endothelial dependent relaxation of mesenteric
arteries in male FGR offspring.

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