Theme C lecture 2 Flashcards
What controls fetal growth during development?
Genetic factors: 15% on genotype and 2% on sex.
Hormonal factors: IGFs, thyroid hormones, insulin promote fetal growth whereas glucocorticoids inhibit fetal growth.
*Growth Hormone is not a main contributor to fetal growth.
What life factors control fetal growth?
High altitude/hypoxia/oxygen deprivation (decreases fetal body weight)
Hyperthermia (reduce fetal growth
Maternal Exercise (reduce fetal growth)
Substance abuse/alcohol/drugs/smoking/toxins (reduce fetal growth)
Maternal disease (some decrease some increase)
Olihydramnios/multiple pregnancy/ fetal malformations (decrease fetal growth)
stress/hormones/fetal infection (decrease fetal growth)
What are some examples of intrauterine growth restricting conditions?
Pre eclampsia
Bleeding; anemia
Renal and heart diseases
Convulsions
Diabetes mellitus
coagulation
Intrauterine fetal death
What are the definitions of Intrauterine growth restriction (IUGR)?
low term birth weight (2.5 kgs): 2% of term babies.
Small-for-gestational age (IUGR):
What is the incidence of Intrauterine growth restriction (IUGR)?
2 - 10% of babies
What is the problem with a small birth weight?
it causes 2 - 3 times more perinatal mortality
What are the main causes of Intrauterine growth restriction (IUGR) in developed and developing countries?
Developed: Uteroplacental insufficiency (Western Society)
Developing: Maternal undernutrition
Other causes include maternal disease and genetic problem
What is fetal programming?
Exposure to suboptimal environment causes adaptations that may help the fetus survive in the short term but leads to increased susceptibility of deceloping some diseases in adulthood.
What are the critical developmental periods which influence fetal programming?
Perincoception / preimplantation
Implantation / placental development
Organogenesis / maximal fetal growth
prepartum maturation (maturation after organogenesis and before birth)
suckling / postanatal / infancy
after weaning / childhood
After puberty / adolscence
What are the problems that are more prominent in smaller fetuses and are influenced by fetal programming?
Hypertension
Coronary heart disease
Stroke
Atherosclerosis
Coagulation disorders
What mechanisms are involved in programming cardiovascular diseases?
Organs: Heart; vasculature; kidney; brain
Systems: Renin-angiotensin system; HPA axis
Alterations: Reduced cell numbers, altered organ structure, altered set points, altered hormone sensitivity
What heart problems are seen in adults born small?
Cardiac hypertrophy
Hypertension
Coronary heart disease
Altered cardiac genes
What are the hypothalamic HPA axis differences seen more often in adults of small birth weight?
Higher plasma cortisol levels
Altered mineralo and glucocorticoid receptors
Greater hypothalamic pituitary adrenal axis responsiveness to ‘stress’
Altered renal function
hypertension
What are the differences in vasculature seen in adults born small?
Altered vascular/endothelial reactivity to vasoconstrictors and vasodilators. (reduced responsiveness)
Increased vessel stiffness
Predisposition to atherosclerosis (hypertension)
What are the differences in kidneys seen in adults born small?
Human and animal models have shown to have a smaller nephron number and higher blood pressure
What happens to heart size of smaller fetuses?
hearts are smaller in smaller fetuses relative to their body weight compared to normal babies.
What is the difference in this effect between males and females?
Males are more prone to heart problems than females due to low birth weight. Females develop hypertension 18 months
What is the result of uteroplacental insufficiency?
Offspring are born small
maternal endocrine environment is altered
mammary development is impaired
Early lactogenesis
poor milk quality and quantity
What is the problem of impaired lactation nutrition?
impaired lactation nutrition compromises postnatal growth with consequences for adult disease development.
What happens to glomerular volume in males during adulthood?
They become larger while staying at a low number. This results in an increase in hypertension.
*This does NOT happen in females.
What happens to glomerular volume in females during adulthood?
In females there is a decrease in glomerular number but no change in glomerular volume. No hypertension in females. (even at 18 months)
What happens to cardiomyocyte numbers in mice?
Males develop less cardiomyocytes
Females don’t develop less cardiomyocytes
What is the effect of early and late accelerated growth on disease?
early accelerated growth is protective against disease whereas late accelerated growth is detrimental.
What is the function of leptin?
leptin regulates adiposity and appetite and acts to reduce food intake and increase activity
Where does leptin act?
hypothalamus
What leptin levels cause obesity?
very low or very high leptin levels
What is the mechanism of leptin’s action?
leptin binds to receptor on cell membrane. Other proteins get turned on and in turn gene transcription is increased.
What is the function of leptin in human babies?
Human babies have a leptin surge prior to birth. Leptin goes to human levels after 35 days.
Leptin is critical in the development of the kidneys
What happens to leptin levels in growth restricted rats?
growth restricted rats have low protein and as a result a low leptin surge
What are the consequences of the reduced leptin surge?
Growth restricted offspring
Reduced nephron endowment
Increased BP in males and cardiovascular disease risk
Does restoring leptin surge restore nephron endowment?
Yes, cross fostering improves nephron endowment
What is the effect of cross-fostering on leptin signalling?
Cross-fostering does restore altered kidney development but signalling does not assist in restoring leptin signalling.
