Topic 2: Pre-eclampsia and offspring Neurodevelopment

Question 1

risk factors for pre eclampsia

Answer 1

advanced maternal age, obesity, diabetes, chronic hypertension

Question 2

symptoms of PE

Answer 2

Onset of chronic hypertension on or after 20 weeks gestation, commonly occurs with proteinuria, placental insufficiency, endothelial dysfunction, systemic inflammation, and organ damage

Question 3

treatment for PE

Answer 3

delivery of placenta and baby

Question 4

effects on mother if untreated?

Answer 4

liver, kidney, brain damage, eclampsia, death

Question 5

what do children born to a mom with PE have an increased risk of developing later in life?

Answer 5

cardiovascular disease, obesity, asthma, and stroke

Question 6

what risk is increased by 30-35% in babies born to a PE mother?

Answer 6

ASD ID and ADHD

Question 7

what has been observed in neuroimaging studies?

Answer 7

altered regional but not total grey matter volumes, altered structural and functional connectivity, reduced white matter maturation

Question 8

what has been observed in offspring of rodent models of PE

Answer 8

behavioural deficits, altered regional brain volume, reduced neurogenesis and oligodendroligogenesis, altered brain transcriptome

Question 9

risk genes for PE

Answer 9

Not well understood, mostly genes involved in endothelial function like VEGF, or cytokine signalling like ERAP1

Question 10

what are the risk genes for ASD?

Answer 10

complicated, Shank and neuroligin genes or TFs that regulate neurodevelopment like FoxP1 and MeCP2

Question 11

birth complications of PE associated also with neurodevelopmental disorders

Answer 11

preterm birth, low birth weight, intrauterine growth restriction

Question 12

name the potential mechanisms of the association of PE and neurodevelopmental disorders

Answer 12

epigenetics, microbiota, placental nutrient transfer, impaired angiogenesis, perturbed placental signaling systems, inflammation, oxidative stress

Question 13

nutrient levels in PE new-borns

Answer 13

decreased nervonic acid (males esp.), lower DHA, higher total and specific amino acids, increased homocysteine levels, altered placental expression of certain transporters

Question 14

describe two important events in PE that cause placental insufficiency

Answer 14

shallow trophoblast invasion and failure to remodel spiral arteries of the myometrium

Question 15

what angiogenic factors (pro and anti) are impacted in PE

Answer 15

VEGF and PIGF are decreased — these are proangiogenic
s-Flt1 and sENG are increased — these are antiangiogenic

Question 16

what are the consequences of impaired angiogenesis in the foetal brain

Answer 16

impaired development of cerebrovasculature leading to oxygen and nutrient deprivation to developing brain, also affects BBB development and permeability

Question 17

prenatal stress and maternal immune activation, how does this impact the developing brain

Answer 17

women with pre-eclampsia exhibit higher levels of stress, placental HSD11B2 expression is decreased in PE placenta, not as much cortisol converted to inactive cortisone, cortisol enters fetal circulation
maternal immune activation is sustained activation of the immune system of the mother during pregnancy, increase in cytokines in both maternal and fetal circulation, elevated IL-6 associated w PE

Question 18

describe the placental serotonin system

Answer 18

the placenta synthesizes 5-HT from maternal tryptophan at a time where the fetus has the 5-HT receptors but cannot make its own serotinin.

Question 19

how is the placental serotonin system altered in PE

Answer 19

it is altered due to changes in tryptophan metabolism

Question 20

placental neurotrophin system; describe, function, and PE effect

Answer 20

placenta makes and secretes neurotrophic factors like BDNF, NT-3, NT4, NGF
BDNF esp. is an essential regulator of neurodevelopment processes
PE: there is decreased BDNF and increased NGF in maternal and fetal circulation

Question 21

in PE, cortisol is __, 5HT is ___
and BDNF is ____, and NGF is _____

Answer 21

in PE cortisol is increased, so is 5-HT, BDNF is decreased and NGF is increased

Question 22

describe normal oxidative stress vs oxidative stress in PE

Answer 22

cells constantly generate reactive oxygen species (ROS) mostly as a biproduct of oxidative phosphorylation in the mitochondria. the cell has antioxidant systems to counteract/balance this ROS. these enzymes include superoxide dismutase, catalase, and molecules like vitamin C and E.
when ROS are high, they exceed the cell’s antioxidant systems, ROS are highly reactive and will damage membrane phospholipids, proteins, and DNA if not counteracted.

Question 23

oxidative stress effect on PE fetus

Answer 23

oxidative stress causes the placenta to release unknown mediators that impact neuronal development of the fetus.

Question 24

what does ROS regulate normally in fetal brain

Answer 24

neural progentior cell proliferation, differentiation, axonal guidance.

Question 25

what is observed in animals with oxidative stress

Answer 25

suboptimal neurodevelopment

Question 26

what are epigenetics?

Answer 26

heritable changes to gene expression, do not affect the actual gene expression, can include methylation of DNA and phosphorylation of histones

Question 27

effect of prenatal stressors on fetal epigenetics

Answer 27

v little research but can affect the fetus neurodevelopment

Question 28

what has been observed in the gut and vaginal microbiota of women with PE

Answer 28

Altered gut and vaginal gut microbiome

Question 29

how does PE affect breast milk

Answer 29

decreased BDNF, increased nervonic acid and DHA

Question 30

what mediates the effect of oxidative stress in PE on neurons

Answer 30

astrocytes and glutamate