Chapter 83 – Foetal Physiology

Abstract

Exchange of nutrients. The placenta is an unusual organ because it is derived from the tissues of two different organisms: endometrial cells (known as decidual cells in pregnancy) from the mother and trophoblastic cells from the foetus. The foetus is entirely reliant on exchange with the maternal circulation for nutrition (supply of O2, glucose, amino acids, etc.) and excretion (elimination of CO2, urea, creatinine, uric acid, etc.).

Chapter 83 Foetal Physiology

What are the functions of the placenta?

The placenta has the following functions:

Exchange of nutrients between the foetal and maternal circulations;
Endocrine;
Immunological.

How does the anatomy of the placenta relate to these functions?

Exchange of nutrients. The placenta is an unusual organ because it is derived from the tissues of two different organisms: endometrial cells (known as decidual cells in pregnancy) from the mother and trophoblastic cells from the foetus. The foetus is entirely reliant on exchange with the maternal circulation for nutrition (supply of O₂, glucose, amino acids, etc.) and excretion (elimination of CO₂, urea, creatinine, uric acid, etc.). Key features of placental development are:
1. – The foetal cells form a ball of cells – the blastocyst – which implants within the endometrium.
2. – The placenta develops from trophoblast cells, derived within the outer cell layer of the blastocyst.
3. – The trophoblastic cells develop into two layers, which together form the chorion. The outer chorionic layer consists of syncytiotrophoblast cells, whilst the inner layer is made up of cytotrophoblast cells.
4. – The chorion invades the maternal decidua, releasing enzymes that produce cavities within the decidua. When the maternal spiral arteries (which supply the decidua) are invaded, their blood fills these cavities.
5. – Projections called chorionic villi form an extensive network of finger-like chorionic projections into the blood-filled cavities and then become vascularised.
6. – When the foetal heart becomes active at 5 weeks’ gestation, foetal blood supplies the placenta through the two umbilical arteries. The umbilical arteries give rise to chorionic arteries, which branch over the foetal surface of the placenta until the capillaries of the chorionic villi are reached. The capillaries of the chorionic villi converge and return blood to the foetus through a single umbilical vein.
The foetal and maternal blood are thus separated only by the foetal endothelium and two (syncytiotrophoblastic and cytotrophoblastic) chorionic cell layers. Nevertheless, there is normally no mixing of maternal and foetal blood. The placenta grows to match the increasing nutritional demands of the developing foetus. As a result, at term, uterine blood flow has increased 10-fold over its pre-gestational value to 750 mL/min, with placental blood flow accounting for approximately 85% of this flow.
Endocrine function. The placenta is an important endocrine organ during pregnancy, producing both peptide and steroid hormones. Hormone production takes place in syncytiotrophoblast cells. The hormones produced are:
1. – β-human chorionic gonadotropin;
2. – Human placental lactogen;
3. – Oestrogen;
4. – Progesterone.
The roles of these four hormones in pregnancy is more fully discussed in Chapter 82.

Clinical relevance: pre-eclampsia

Pre-eclampsia is a potentially life-threatening complication of pregnancy characterised by hypertension and proteinuria in the third trimester. Pre-eclampsia has many associated complications including: eclampsia, HELLP (Haemolysis, Elevated Liver enzymes and Low Platelet count) syndrome, liver rupture and cerebral haemorrhage.

The exact pathogenesis of pre-eclampsia is not yet fully established. A possible sequence of events is:

There is dysfunction of the spiral arteries that constitute the sole blood supply of the placenta. It is not clear whether this is due to foetal (e.g. inadequate trophoblast invasion) or maternal factors.
The syncytial cells of the chorion – the endocrine cells of the placenta – produce a number of substances in response to hypoxia. These include cytokines, eicosanoids and the soluble vascular endothelial growth factor receptor 1. There is also an increased rate of apoptosis of syncytiotrophoblast cells.
These released placental factors cause a systemic inflammatory response in the mother, resulting in widespread endothelial dysfunction and subsequent organ dysfunction.

The only definitive treatment of pre-eclampsia is delivery of the placenta; the risks of pre-eclampsia to the mother must be balanced against the early delivery of the foetus.

Immunological function. The foetus is genetically distinct from the mother and would accordingly be expected to provoke a maternal immune response. However, this rarely occurs, and this immune tolerance is attributed to the placenta:
1. – After implantation, trophoblast cells lose many of their cell surface major histocompatibility complex molecules, making them less immunogenic. The trophoblast cells cover themselves in a coat of mucoprotein, further disguising them from the maternal immune system.
2. – The chorionic cells act as an immunological barrier, preventing maternal T cells and antibodies from reaching the foetal circulation.
3. – Progesterone and α-fetoprotein produced by the yolk sac at implantation act as maternal immunosuppressive agents, specifically damping down cellular immunity. However, this also decreases the ability of the mother to launch effective cell-mediated reactions in defence against certain microorganisms, such as Listeria monocytogenes.
The chorion also acts as a barrier to prevent bacteria and viruses infecting the foetus. However, some bacteria (e.g. Listeria) and many viruses (including rubella, parvovirus B19 and HIV) manage to cross into the foetal circulation. The foetal immune system is not fully developed until 6 months after birth. In utero, the foetus relies on maternal antibodies to fight infections: syncytiotrophoblasts have immunoglobulin G (IgG) receptors, allowing IgG, but not other forms of immunoglobulin, to cross the placenta by endocytosis.

Clinical relevance: placental antibody transfer

The foetus requires maternal IgG as a defence against infections. However, allowing the placental transfer of IgG also has negative consequences:

Haemolytic disease of the newborn. Rhesus (RhD) antigen-negative mothers previously exposed to the RhD antigen (e.g. through blood transfusion or previous foetomaternal haemorrhage) produce anti-RhD IgG. When pregnant with an RhD-positive foetus, maternal anti-RhD IgG crosses the placenta and attacks foetal erythrocytes, resulting in haemolysis.
Transient neonatal myasthenia. Myasthenia gravis is an autoimmune condition in which the immune system produces IgG against the acetylcholine receptors of the neuromuscular junction, causing fatigable muscular weakness (see Chapter 53). Placental transfer of these antibodies causes some neonates to have temporary muscle weakness, resulting in respiratory distress, a weak cry and poor feeding.
Congenital heart block. Placental transfer of anti-Ro IgG antibodies from mothers with systemic lupus erythematosus can cause congenital heart block and neonatal lupus erythematosus.

What are the different mechanisms by which substances cross the placenta?

Substances may cross the placenta through different mechanisms:

Simple diffusion of gases, particularly O₂ and CO₂.
Facilitated diffusion. Glucose crosses the placenta through facilitated transport by the insulin-independent glucose transport proteins GLUT-1 and GLUT-3. Glucose transfer is proportional to maternal glucose concentration and is increased in diabetic mothers with poor glycaemic control, with a consequent high average foetal plasma glucose concentration.
Active transport. Amino acids are transferred across the placenta by Na⁺-dependent active transport. Many amino acids are metabolised in the placenta. For example, serine is converted to glycine before being released into the foetal circulation.
Transcytosis. IgGs are endocytosed by syncytiotrophoblast cells, transferred across the placenta in a vesicle and exocytosed into the foetal circulation.
Bulk flow. In a similar way to other capillary systems in the body, water passes between the cells of the placenta along its osmotic gradient. Any small molecules dissolved in the water are also transported by solvent drag.