Gametes - Physiology of Foetal Growth Flashcards
IU growth - stage 1
Hyperplasia
4-20 weeks
rapid mitosis
increasing DNA content
IU growth -Stage 2
hyperplasia/hypertrophy
20-28 weeks
declining mitosis
increasing cell size
IU growth - stage 3
hypertrophy
28-40 weeks
rapid hypertrophy
rapid increasing cell size
rapid accumulation of fat, muscle, CT
when does symmetrical growth retardation occur
symmetrical => correct ratios
up to 20 weeks
(state of hyperplasia)
when does asymmetrical growth occur
stage 2 and 3
newborn may have larger head in proportion to the rest of the body
slow AC growth vs normal HC and FL
placental insufficiencies ⇒ glycogen utilisation by liver, liver shrinkage, decreased AC - preferential shunting to brain thus maintaining HC
describe physical consequences of symmetrical IUGR
1/3 of all cases
foetus is proportionally small - head circumference (HC), abdominal circumference (AC) and femur length (FL)
change in mean weight as duration progresses with singletons, twins, triplets and quadruplets
small for gestational age vs IUGR
small for others of same gestation - lowest 10th percentile
IUGR - brought about by a pathological reason
6 parameters by which IUGR can be prenatally diagnosed
- maternal history e.g. hypertension, smoking
- maternal examination - measurement of fundal height
- foetal ultrasound
- amniotic fluid vol
- blood flow measurements using a Doppler (blood flow to umbilical cord)
- biochemical data - estriol (low 24 hour urinary estriol excretion is associated with 21% of IUGR infants) and human Placental Lactogen, hPL/human Chorionic Sommatotrophin, hCS (produced by placenta and spares glucose for developing foetus)
risks associated with IUGR
increased perinatal morbidity and mortality x10
- increased foetal distress
- stillbirth
- neonatal hypoglycemia (twitchy movements)
- polycythemia (stimulated by hypoxia)
- meconium aspiration
- hypocalcemia (twitchy movements)
what is foetal growth affected by (3 factors)
genetics
potential genetic code
transcription - phenotype
physical environment
uterine capacity - restrictor
nutrient availability - metabolism
interaction between the 2
hormones
growth factors
transcription factors
what is nutritional regulation of growth regulated by
it is both a reaction to environmental conditions and acting on genetic potential
transfer of material across the placenta
how are AAs transported
against a conc gradient
what are AAs essential for
creation of transporters for moving molecules into conceptus
⇒ lack of functional transporters can lead to deficiency, despite availability
name the AA essential for foetal development
taurine
without a functioning transporter, a foetus can be taurine deficient
role of functional AAs (FAA)
primarily transport proteins
function of FAA Arginine
cell division
healing of wounds
removing NH3 from the body
immune function
release of hormone
function of FAA Cysteine
enzymes and oxidation
donates electron for breakdown of molecules
function of FAA Leucine
leucine is utilised in liver, adipose tissue, muscle
it is the only dietary AA that has the capacity to stimulate muscle protein synthesis
function of FAA glutamine
protein synthesis
regulation of acid-base balance
cellular energy - glucose uptake
nitrogen donation for anabolic rxns
carbon donation
non-toxic transporter of NH3 in the blood circulation
observations when GH is knocked out of mice
normal foetal growth
normal BW
after birth, growth is impaired
⇒ IGF-I and IGF-II are NOT regulated by GH during foetal development
observations when IGF-I is knocked out of mice
slow foetal development
low birth weights
mice also display marked lack of growth after birth as well
⇒ IGF-I is important for growth at all stages of development (before and after birth)
observations when IGF-II is knocked out of mice
slower foetal development with low birth weights
however after birth, mice grow at normal rates
⇒ IGF-II is an important foetal growth factor with unclear role in growth after birth
control of IGF-I
growth hormone
control of IGF-II
nutritional status predominantly
regulation of foetal growth
binding of IGFBP-1 to IGF
IGFBP 1 binds to IGF with a greater affinity than IGF binds to its receptor - decreases its action
binding of IGFBP-3 to IGF
IGFBP-3 facilitates binding of IGF to its receptor - increases its action
regulation of foetal growth in early vs late gestation
no IGF-II
symmetrical restricted growth, as it plays a role in early gestation
IGF-I deficiency
asymmetrical growth restriction due to its role in late gestation
define IUGR
pathological decrease of foetal growth
failure of the foetus to reach growth potential associated with increased morbidity and mortality
BW < 10th or 5th percentile for gestational age
BW < 2.5kg for gestational age
BW < 2SD below the mean value for gestational age
ponderal index
used to identify infants whose soft tissue mass is below normal for the stage of skeletal development
factors affecting IUGR
define TORCH infections
toxoplasmosis
other (syphilis, varicellazoster, parvovirus B19, zika virus)
rubella
cytomegalovirus (CMV)
herpes infections
perinatal infections account for
2-3% of all congenital anomalies
pre-natal foetal undernutrition - what are the factors influencing it
glucose that is present is spared for vital organs ⇒ asymmetrical
if the lack of glucose is severe enough, organs may be affected - pancreas can be underdeveloped
insulin and pregnancy
Normal for mother to become less sensitive to insulin, sparing glucose for foetus, using fat for her energy
foetal salvage hypothesis
hormone levels in a normal foetus vs an IUGR baby
(brain is permanently permeable to glucose so no need for insulin)
what is the key regulator of metabolic homeostasis
primarily mTORC1 - mMechanistic Target Of Rapamycin
cellular processes (IC) are linked to external environmental cues (EC)
nutrient availability and growth factors
factors influencing mTORC1
Inhibition of mTORC1 by rapamycin actually induces stress responses, including reduction in protein synthesis and induction of autophagy, which are protective mechanisms for the cells to survive under stress conditions
⇒ if a foetus undergoes macrosomatic growth (large for gestational age), a rapamycin-like compound may be administered to slow down growth
placenta and foetal growth
maternal circulation and foetal circulation - how is it influenced by mTORC1
transporters present on mTORC
hexose transporters
AA transporters
importance of implantation on day 7
Incorrect formation of arteries and maternal sinuses - don’t get correct blood supply
HP axis if the foetus is put under stress
Combat stress - CRH from hypothalamus
ACTH from ant pituitary
Cortisol from adrenal gland
Foetal adrenal gland is essential
cortisol and parturition
increase in cortisol
To protect foetus from premature labour - 11beta-HSD2
Stress protection enzyme
Converts cortisol into much weaker steroid - cortisone
Normal developing foetus - normal levels of 11beta-HSD2
But not in IUGR
Exposed to cortisol - increased blood sugars, breakdown of proteins to obtain nutrients
risks of being small for gestational age
Increased risk of T2D
Rapid post natal weight gain
Trying to compensate for restricted growth
(Increase in steroids to compensate decrease steroid hormone binding globulins so steroids are free to increase growth)
