Placental function

Question 1

What does the placenta protect the fetus against?

Answer 1

1. Maternal immune system
2. Pathogens
3. Chemicals in maternal circulation

Question 2

How does the placenta protect against the maternal immune system?

Answer 2

1. The placenta acts as barrier to prevent maternal leukocytes from entering fetal circulation
2. Cells of the syncytiotrophoblast in direct contact with maternal blood don’t express MHC class I or II so cannot be easily detected by maternal immune system

Question 3

What are the consequences of abnormal interactions between maternal immune system and placenta?

Answer 3

Poor formation of the placenta, resulting in reduced exchange capacity, increased fetal stress and IUGR.

Question 4

How does the placenta protect against pathogens?

Answer 4

1. The placenta acts as a barrier between most pathogens and the fetus
2. Placenta mediates transport of maternal IgG into fetal circulation and gives fetus passive immunity

Question 5

How does the placenta protect against chemicals in the maternal circulation?

Answer 5

1. The placenta acts as barrier between hormones in maternal circulation and the fetal circulation, mostly due to expression of inactivating enzymes by trophoblast cells (e.g. 11β-HSD inactivates maternal cortisol)
2. Trophoblast cells express P-glycoproteins that are able to transport many chemicals out og fetal circulation (e.g. toxins, drugs…)

Question 6

What are the characterstics of the placenta that make it an efficient site of exchange?

Answer 6

1. Low pressure, high volume of blood flow as a result of conversion of spiral arteries.
2. Large SA for exchange.
3. Presence of many transporter and channel proteins.
4. Constant blood flow to allow for maintenance of high diffusional gradient.

Question 7

What are the general mechanisms by which substances are transported across the placenta?

Answer 7

1. Simple diffusion (trans/paracellular)
2. Facilitated diffusion
3. Active transport
4. Endo-/exocytosis

Question 8

What percentage of O₂ consumed by the fetal-placental unit is used by the placenta?

Answer 8

~30%

Question 9

What is the microstructure of placental villi?

Answer 9

• Thick regions for hormone synthesis
• Thin vasculosyncytial membranes for diffusion

Question 10

What features of the placenta make it good at carrying out gas exchange?

Answer 10

1. Large surface area: Highly branched nature of placental villi.
2. Small diffusion distance: Thin barrier between foetal and maternal blood (~2-3μm).
3. Steep diffusion gradient: Constant supply of maternal blood and intrinsic difference in O₂ conc. in foetal venous blood compare to maternal blood.
4. Double Bohr shift: Bohr shift is phenomenon whereby there is increased O₂ affinity of Hb as result of increase in pH. In placenta, foetal Hb O₂ affinity increases as result of ↑pH due to ↓[CO₂] while maternal Hb O₂ affinity decreases as result of ↓pH due to ↑[CO₂].

Question 11

How is glucose transported across the placenta?

Answer 11

Facilitated diffusion through GLUT transporters that function by utilising the Na+ gradient set up by Na+/K+-ATPase to transport glucose from maternal circulation into foetal circulation against conc. gradient.

Question 12

Why is transport of glucose across the placenta important for fetus?

Answer 12

Only source of glucose as it cannot undergo gluconeogenesis

Question 13

How are amino acids transported across the placenta?

Answer 13

1. System A & ASC
2. System X_AG
3. System L

Question 14

What are the properties of system A and ASC amino acid transport systems?

Answer 14

• Na⁺-independent
• Transports neutral amino acids

Question 15

What are the properties of system X_AG amino acid transport system?

Answer 15

• Na⁺-dependent
• Transports acidic amino acids

Question 16

What are the properties of system L amino acid transport system?

Answer 16

• Na⁺-independent
• Transports neutral amino acids

Question 17

How is IgG transported across the placenta?

Answer 17

• Due to large size of antibody molecules, the only transport system capable of facilitating their transport is endo-/exocytosis. It is therefore the only molecule to be transported across the placenta this way.
• Maternal IgG binds to FcRs on microvillous surface of syncytiotrophoblasts, expecially in pits at the base of microvilli. They enter the trophoblast cells via endocytosis and exit via exocytosis.

Question 18

What are the peptide hormones synthesised by the placenta?

Answer 18

1. hCG
2. hPL
3. PGH
4. Leptin
5. PAPP-A

Question 19

What are the steroid hormones synthesised by the placenta?

Answer 19

1. Oestrogen
2. Progesterone

Question 20

Where is hCG synthesised and what is its function?

Answer 20

• Synthesised by syncytiotrophoblasts.
• Maintains corpus luteum and its production of steroid hormones for endocrine support of embryo at beginning of pregnancy.

Question 21

What is the structure of hCG?

Answer 21

1. α-subunit: Identical to α-subunits of LH, FSH and TSH
2. β-subunit: Unique but similar to LH

Question 22

Where is hPL synthesised and what is its function?

Answer 22

• Synthesised by syncytiotrophoblast.
• Functions:
  1. Stimulates maternal appetite
  2. Induces growth/differentiation of mammary glands

Question 23

What is the structure of hPL?

Answer 23

It is structurally similar to growth hormone (96% homology) and prolactin (67% homology).

Question 24

Where is PGH synthesised and what is its function?

Answer 24

• Synthesised by syncytiotrophoblast
• Functions:
  1. Stimulates lipolysis and gluconeogenesis in mother
  2. Elevates maternal blood glucose levels to promote foetal growth
  3. Suppresses secretion of maternal pituitary growth hormone (presumably to prevent excess levels of GH in mother)

Question 25

Where is leptin synthesised and what is its function?

Answer 25

• Synthesised by syncytiotrophoblast
• Functions:
  1. Stimulates maternal appetite
  2. Stimulates expression of placental transport proteins

Question 26

Where is PAPP-A (pregnancy-associated plasma protein A) and what is its function?

Answer 26

• Synthesised by syncytiotrophoblast
• Functions:
  1. It is a protease that cleaves IGFBP and enhances their bioavailability
  2. Has the overall effect of promoting local proliferative processes

Question 27

Where is progesterone synthesised and what is its function?

Answer 27

• Synthesised by syncytiotrophoblast
• Functions:
  1. Inhibits uterine contractions
  2. Stimulates maternal appetite
  3. Stimulates secretions from endometrial glands
  4. May also have immunomudulatory role

Question 28

What is the process of oestrogen synthesis?

Answer 28

1. Cholesterol from maternal circulation is converted to pregnenolone in the placenta.
2. It is conjugated with sulfates in the fetal adrenal glands and liver.
3. Conjugated steroids then deconjugated and converted to steroid derivatives by the fetal adrenal glands.
4. Derivatives are then converted to oestrogens by the placenta (incl. oestradiol, oestrone & oestriol)

Question 29

Levels of which oestrogen is used as an indicator of fetal health and why?

Answer 29

Oestriol is derived from 16α-OH androstenedione from fetal liver only. Its levels in maternal blood are therefore directly related to fetal health, compared to other oestrogens that are synthesised by both fetus and mother.

Question 30

What is the function of steriod conjugation by the fetus?

Answer 30

• The fetus conjugates steroids with sulfates while the placenta deconjugates them and releases them back into maternal blood.
• Conjugated steroids are inactive and soluble, so this system allows for high levels of steroids in maternal blood without the risk of affecting fetal development (e.g. masculinisation of females).