Placental Function Flashcards
How does placental growth change during pregnancy?
1ST Trimester
• Development of villous trees
• Rapid growth
2nd-3rd trimester
• Slower placental growth
• Changes in structure
• Increases in efficiency
• Fetal growth overtakes placental growth from mid pregnancy → fetus gains 250g a week in 3rd trimester (exponential growth).
What synthesises hormones in the placenta, and what are these hormones?
• ST is a single multinucleated cell that surrounds the entire surface
• Highly specialized for nutrient and gas exchange and hormone production
• ST synthesizes a range of hormones:
− hCG → important for establishing pregnancy, so spike early on.
− Placental lactogen
− Placental growth hormone
− Progesterone
− Estrogen
• Secreted into the maternal blood
• Hormones (apart from hCG) increase as placental size increases
What are the functions of placental hormones?
• hCG
− Produced from early trophoblast cells
− Prevents regression of the corpus luteum
− Essential for establishment of pregnancy
− Measuring hCG is a marker of a normal placenta
− Detectable in blood 24-48 hours after implantation
− Levels should double every 48 hours
− Linked to morning sickness
− Low levels in failing pregnancies
− High levels in Down’s (not diagnosable, but risk factor)
Steroid Hormones
• Progesterone
− “pro gestation’ – essential for pregnancy
− Blocked (mifepristone) to induce termination
− Primes endometrium for implantation (decidualisation)
− Endocrine switch – placenta takes over production from corpus luteum
− Inhibits myometrial contractility (prevents preterm labour)
− Removal of effects is essential for labour
− Strengthens cervical mucous plug to prevent infection
− Stimulates growth of breast tissue
− Metabolic effects
• Estrogen
− Stimulates growth of breast tissue
− Stimulates myometrial growth (uterus expanding to accommodate fetus)
− Increases uterine blood flow
Maternal Metabolic Adaptations
• ‘Parasitic’ fetus – competition for glucose during time of rapid fetal growth
• Placental hormones rewire maternal metabolism to priorities fetal needs
• Early in 2nd trimester, placenta adapts maternal metabolism so the mother gains fat stores
• 3rd trimester – mother uses fat stores to produce energy, preserving glucose for fetus
• Progesterone, placental lactogen and placental growth hormone cause insulin resistance in the mother → reduces maternal glucose uptake so it is taken up by the fetus instead.
What is the impact of drug use in pregnancy?
- 65% pregnant women in the UK given prescription drugs
- In the US, 10% given potentially harmful prescription drugs
- A teratogen is something that causes damage to a developing fetus
- Drugs classified according to teratogenic risk
Impact of drug use
• Epileptic drugs associated with birth defects → cardiac, orofacial, gastrointestinal, neural tube
• Affects 4% epileptic pregnancies
• Illicit drug use estimated to be around 10-16% → related to early pregnancy loss, premature birth, low birth weight and congenital abnormalities.
What helps protect the fetus against drug use?
Multidrug Resistance Proteins
• Potential family of receptors important for protection of the fetus on the ST surface
• Cell surface transporters eg) MDR-1, BCRP
• Selectively efflux toxins out of the placenta →xenobiotics, heavy metals, PhIP (carcinogen in red meat), cigarette smoke, carcinogens, flavones
• Protects the fetus
• Variable expression levels → may be able to tell which babies more susceptible depending on levels of receptors.
How does the fetus avoid immune rejection by the mother?
• Fetus is semi-allogeneic – half the genes from the father, so foreign to mother
Why is it not rejected?
• Altered maternal immune system in pregnancy → switch to type 2 response, less likely to have an inflammatory reaction
• MHC-I antigens not expressed by the ST → these are the antigens they try to match during a transplant. Placenta doesn’t express them, so hides from the immune system.
How is the fetus protected against infection?
Hoffbauer Cells:
• Fetal macrophages in the placenta
• In early pregnancy, derived from villous mesenchymal stem cells
• In late pregnancy, derived from the recruitment of fetal monocytes
• Believed to promote placental angiogenesis → source of angiogenic factors and in close contact with developing vessels
• Have proposed roles in host defense:
− Phacogytosis of apoptotic bodies and cellular debris
− Antigen presentation in response to infection
− Prevention of vertical transmission of infection from the fetus to the mother (eg, HIV)
• More abundant in early pregnancy and pregnancy pathologies (eg diabetes, rhesus disease and viilitis (infection of villi, placenta rejected).
How do substances transfer across the placenta by simple diffusion?
• Ficks law → diffusion rate is proportional to the concentration gradient, surface area of the membrane, and inversely proportional to the thickness of the membrane.
• Permeability of the human placenta to hydrophilic solutes:
− Inverse relationship with size → larger the solute, lower the rate of diffusion
− The permeability surface area product is a marker of the rate of passive permeability (eg, diffusion).
− Hemochorial placentas have a higher passive permeability than epitheliochorial placentas → epitheliochorial placentas have more layers between maternal and fetal blood
− Small molecules such as creatinine have a high rate of diffusion
− AFP is one of the larger molecules with a slow rate of diffusion
− Part of Downs syndrome screening
Shouldn’t be in maternal blood, but if the placental is leaky, it diffuses across
How do substances pass across the placenta by transcellular facilitated diffusion?
eg) Glucose
• Via GLUT1 transporters
• Maternal plasma concentration higher – diffuses down a concentration gradient
How do substances pass across the placenta by receptor mediated endo/exocytosis?
eg) Ig, Transferrin
• Antibodies transmitted from the mother to the fetus in the third trimester to give the baby immune protection when it is born
• Iron also transported via transferrin
How do ions transport across the placenta?
eg) Calcium
• Concentration in maternal blood is in the milimolar range, in the trophoblast it is micromole → gives concentration gradient
• Calcium enters via voltage gated calcium channels on the microvillous membrane
• Transported through the trophoblast by calcium binding proteins
• It then has to go up a concentration gradient (high concentration in the fetus due to developing bones) so it requires active transport into the fetal circulation using the calcium ATPase pump
How do substances pass across the placenta by active transport?
eg) System A amino acid transporter
• Amino acids are another fuel source for the baby
• Around 20aa transporters – one of them is system A
• Transports small, neutral amino acids (glycine, alanine, serine)
• Co-transports them into the cell alongside sodium
• Is selective, specific and requires energy
What are two types of impaired fetal growth?
• FGR − 5-5% pregnancies − Still birth − Neonatal mortality and morbidity − Lifelong disability − adult ill-health • Macrosomia − Operative delivery − Should dystocia − Fetal trauma − Impaired glucose tolerance
What are the 4 ways abnormal placental function can cause FGR?
• Abnormal placental function can cause FGR because it is the result of insufficient nutrients transferring across the placenta (reduced placental nutrient transfer capacity) due to:
− small/abnormal placental structure (reduced surface area)
− reduced maternal blood perfusion
− impaired placental blood flow
− reduced activity of nutrient transporters
How is maternal blood flow involved in FGR?
• Maternal blood delivered to placenta through uterine spiral arteries
• High volume at low resistance
• Made possible by the transformation of the uterine arteries in early pregnancy by extravillous trophoblasts
− Enlarged sinus
− High volume
− Low resistance
Abnormal maternal blood flow
• In FGR and pre-eclampsia – could be failure of transformation of spiral arteries giving reduced flow, high resistance and diastolic notching
• Leads to reduced oxygen and nutrient supply
• Diagnosed using uterine artery Doppler
• In FGR → much more of a sharp peak. Notch indicating elastic recoil – suggests vessels have not been remodeled properly
