The Placenta

Question 1

In which phase of the menstrual cycle does a blastocyst implant into the endometrium?

Answer 1

• The blastocyst implants into the endometrium in the mid-luteal phase, when oestrogen and progesterone are high.
• The implantation window is day 19-24 of menstruation.

Question 2

What are pinopodes?

What is their function?

Answer 2

• Pinopodes are the structures formed by the swellings of the endometrium surface, which is normally covered with cilia.
• Pinopodes function to trap the blastocyst into the endometrium, as they replace the cilia that normally beat the blastocyst across the endometrium.
• They are indicative of the implantation window.

Question 3

Give a chronological overview of the events preceding implantation, starting from fertilisation.

Answer 3

• Day 0: Fertilisation occurs at the ampulla.
• Day 1-3: The first, second and third cleavages occur to produce an 8-cell uncompacted morula.
• Day 4: An 8-cell compacted morula forms.
• Day 5: The early blastocyst forms, consisting of an inner cell mass, a blastocoel (fluid-filled cavity) and trophectoderm (the precursor to the placenta that provides nourishment).
• Day 6-7: Zona hatching occurs and the zona pellucida degenerates.
• Day 8-9: The blastocyst implants into the endometrium.

Question 4

Describe the process of blastocyst implantation into the endometrium.

Answer 4

1 - Apposition - initial loose association of the blastocyst with the uterine wall.

2 - Attachment - subsequent firm adhesion of the blastocyst to the uterine wall.

3 - Invasion - the blastocyst initiates enzyme production to degrade and invade the glycogen-rich endometrium, providing further nutrient support.

Question 5

What is decidualisation?

Answer 5

• Decidualisation is the process by which the endometrium undergoes morphological and biochemical changes in preparation for implantation.
• It is induced by progesterone.
• It is marked by:

1 - Oedema.

2 - Changes in the extracellular matrix.

3 - Vascular remodelling.

4 - Uterine natural killer cell infiltration.

5 - Glycogen and lipid uptake.

6 - Secretion of decidual proteins.

7 - Transformation of fibroblast-like cells to secretory epithelial cells.

Question 6

List 4 decidual proteins secreted by the endometrium during decidualisation.

Answer 6

1 - Prolactin.

2 - IGFBP-1.

3 - Tissue factor.

3 - VEGF.

Question 7

What is the function of uterine natural killer cells?

Answer 7

• Uterine natural killer cells infiltrate the endometrium in preparation for implantation to prevent an autoimmune response against the blastocyst.
• There are no T cells at the site of implantation.

Question 8

List the types of trophoblast to which the trophectoderm gives rise.

Answer 8

The trophectoderm gives rise to:

1 - Villous cytotrophoblasts.

2 - Syncytiotrophoblasts.

3 - Extravillous trophoblasts.

*The function of each type is explained later in the lecture.

Question 9

How does the syncytiotrophoblast form?

Answer 9

The syncytiotrophoblast forms as a result of fusion of villous cytotrophoblasts.

*The syncytiotrophoblast doesn’t completely replace the villous cytotrophoblasts - they both exist in the developing embryo.

Question 10

Describe the structure of the placenta.

Answer 10

Placenta microstructure:

• The placenta is split into many lobes, each contained within syncytiotrophoblastic shells.
• Within the lobes are many chorionic villi, which lie in a pool of maternal blood in intervillous spaces. They are the site of exchange between maternal and foetal blood and are formed of villous cytotrophoblastic cells.
• The intervillous spaces are supplied with maternal blood by the endometrial spiral arteries and endometrial veins. The blood crosses the syncytiotrophoblast shell to reach the chorionic villi.

Placenta gross structure in relation to the amniotic sac:

• The placenta surrounds the amniotic sac.
• The amniotic sac is separated from the placenta by the amniochorionic membrane, which is composed of an outer chorion (part of the placenta) and an inner amnion (part of the amniotic sac).
• The vessels of the chorionic villi fuse at the chorion to form the umbilical cord, which projects towards the embryo in the amniotic sac.
• The amniotic sac receives nutrients from the foetal circulation, which derives nutrients from the chorionic villi.

Question 11

Why is the human placenta considered to be haemochoroidal?

Answer 11

The human placenta is considered to be haemochorodial because the chorion is in direct contact with maternal blood.

*This is best because it offers the shortest diffusion distance.

Question 12

How does the blastocyst derive nutrients before the formation of the placenta?

Answer 12

• Before placenta formation, the blastocyst derives nutrients and oxygen by diffusion from the surrounding decidua in which it is implanted.
• This is known as histiotrophic nutrition.

Question 13

Describe the process of early placental formation.

Answer 13

• In early placental formation, the syncytiotrophoblast invades and erodes maternal capillaries.
• Separate pores then form in the syncytiotrophoblast, known as lacunae.
• The lacunae anastomose with the maternal vessels, forming sinusoids, which eventually form the intervillous spaces.
• The cytotrophoblasts invade the syncytiotrophoblast to form finger-like projections between the sinusoids. These structures are the primary chorionic villi.
• Extraembryonic mesoderm from the inner cell mass invades the core of the primary villi. The primary villi are now secondary chorionic villi.
• The mesoderm differentiates to form endothelial cells, which fuse with the band of mesoderm known as the embryonic stalk (later the umbilical cord) to link the foetal blood system to the maternal blood system. The secondary villi are now tertiary chorionic villi.

Question 14

How does the microstructure of the tertiary chorionic villi of the placenta change over time as the placenta matures?

Answer 14

• The mature chorionic villi form stem villi, which are the basal villi attached to the chorion.
• Branch villi project from the sides of stem villi.
• Terminal villi are the swellings at the tips of branch villi. They are the sites where most exchange takes place.

Question 15

What are anchoring villi?

Answer 15

Anchoring villi are villi that cross the intervillous space deep into the maternal decidua to anchor the placenta to the endometrium.

Question 16

How does the extravillous trophoblast form?

Answer 16

• Cytotrophoblasts at the end of the anchoring villi proliferate and differentiate to form the extravillous trophoblast.

Question 17

List 2 functions of extravillous trophoblasts.

Answer 17

1 - Extravillous trophoblasts remodel spiral arteries in preparation for pregnancy.

2 - Extravillous trophoblasts communicate with uterine natural killer cells to establish immune tolerance to the blastocyst.

Question 18

Why and how do spiral arteries remodel during embryo development?

Answer 18

Function:

• Spiral arteries must remodel to supply a low-resistance, high-flow supply of blood to the intervillous spaces.
• They are remodelled by extravillous trophoblasts:

1 - They dilate to increase the diameter 10-fold

2 - They lose their spiral morphology.

3 - The vascular smooth muscle is removed (to ensure the spiral arteries aren’t subject to maternal vasoregulation).

Mechanism:

• Initially, extravillous trophoblasts form a plug to block the spiral arteries, reducing the blood flow to the developing placenta.
• This gives the arteries time to remodel.
• This also creates a low oxygen environment, protecting the foetus from oxidative stress.
• Extravillous trophoblasts that remodel the inner walls of the arteries are known as endovascular extravillous trophoblasts, whereas extravillous trophoblasts that remodel the outer walls of the arteries are known as interstitial extravillous trophoblasts.
• Endovascular extravillous trophoblasts destroy and replace the endothelial cells, taking on an endothelial phenotype.
• Interstitial extravillous trophoblasts destroy the smooth muscle and replace it with fibrous tissue.
• At 14 weeks of gestation, the extravillous trophoblast plugs breakdown, initiating blood flow into the intervillous space.
• Later in pregnancy, endothelial cells migrate back into the spiral arteries and replace the endovascular extravillous trophoblasts.

Question 19

List 7 molecules that are transported into the placenta from the maternal blood by diffusion.

Answer 19

Diffusion:

1 - Oxygen.

2 - Carbon dioxide.

3 - Na+.

4 - Urea.

5 - Fatty acids.

6 - Glucose.

7 - T4.

Question 20

List 3 molecules that are transported into the placenta from the maternal blood by active transport.

Answer 20

Active transport:

1 - Amino acids.

2 - Iron.

3 - Ca2+.

Question 21

Give an example of a molecule that is not transported into the placenta from the maternal blood.

Answer 21

Conjugated steroids are not transported into the placenta from the maternal blood.

Question 22

List 4 harmful molecules that are able to be transported into the placenta from the maternal blood.

Answer 22

1 - Alcohol.

2 - Caffeine.

3 - Cocaine.

4 - Tetracycline.

Question 23

List 4 maternal adaptations to the increasing oxygen / nutrient demand of the foetus.

Answer 23

1 - Uterine blood flow increases 20 fold via the uterine and ovarian arteries. This increases blood flow to the umbilical arteries and veins, and therefore to the chorionic villi.

2 - Cardiac output increases by 30%.

3 - Maternal blood volume increases by 40%.

4 - Ventilation rate increases.

Question 24

How does the Bohr effect differ in foetal haemoglobin?

How does this affect the pH of foetal blood?

Answer 24

• Foetal haemoglobin has a higher affinity for oxygen, and therefore achieves saturation at a lower pO2 (the Bohr diagram will look steeper).
• The movement of O2 is met by a simultaneous movement of CO2 in the opposite direction.
• Therefore, the foetal pH will be higher because a lower pO2 is required for saturation of the RBCs, so there will be less O2 in the plasma and therefore less CO2 in the plasma, meaning the equilibrium will shift from H+ + HCO3- to H2O + CO2.

Question 25

How is glucose absorbed by the foetus?

Answer 25

- Uptake of glucose into the foetus is controlled by insulin-insensitive hexose transporters GLUT1 and GLUT3. * This doesn't mean that foetal glucose concentration is independent of maternal insulin, as maternal insulin still regulates maternal glucose.

Question 26

How are amino acids absorbed by the foetus?

Answer 26

- The foetus regulates maternal amino acid metabolism through progesterone. - The mother transports extra amino acids (produced by an increase in metabolism due to progesterone) to the foetal circulation.

Question 27

How is foetal urea excreted?

Answer 27

The foetal urea diffuses passively into the maternal blood for removal.

Question 28

Which tissue of the placenta forms the primary barrier to nutrients?

Answer 28

The syncytiotrophoblast forms the primary barrier to nutrients. * This is where the GLUT channels and amino transporters are found. * Remember blood must travel through the syncytiotrophoblast before reaching the chorionic villi.

Question 29

How is water absorbed by the foetus?

Answer 29

Water exchange occurs both in the placenta and in the non-placental tissue at the amnion. *Na+ and other electrolytes transfer across the placenta with water.

Question 30

List 5 pathogens that cross the placenta.

Answer 30

Viruses: 1 - Cytomegalovirus. 2 - Rubella. 3 - HIV. Bacteria: 4 - Spirochetes (avoid unpasteurised cheese!). Protozoa: 5 - Toxoplasma (avoid cat shite!).

Question 31

Which antibody is transferred from the maternal blood to the foetus? How is it transferred?

Answer 31

IgG is transferred to the foetus by pinocytosis.

Question 32

What is IUGR? What causes it?

Answer 32

- IUGR is intrauterine growth restriction of the foetus. It is caused by abnormal placentation: 1 - Insufficient penetration of the extravillous trophoblasts, leading to poor remodelling of the spiral arteries. 2 - Shallow invasion of the syncytiotrophoblast into the decidua. - This results in foetal hypoxia, reduced amino acid transport and reduced fatty acid transport. - Glucose transfer is not affected.

Question 33

Give an example of how extravillous trophoblasts can cause miscarriage other than by intrauterine growth restriction (IUGR).

Answer 33

Premature loss of extravillous trophoblast plugs in the spiral arteries can cause early initiation of blood flow to the placenta, which may lead to miscarriage.

Question 34

List 4 effects of poor remodelling of the spiral arteries on the foetus and blood flow to the chorionc villi.

Answer 34

1 - Damage to the villi. 2 - High pressure flow to the chorionic villi. 3 - Pulsatile flow to the chorionic villi caused by vasoconstriction. 4 - Ischaemia.

Question 35

What is preeclampsia? What causes it? What proportion of pregnancies result in preeclampsia?

Answer 35

- Preeclampsia is a maternal systemic syndrome caused by abnormal placentation in the first trimester, which results in release of various factors from the placenta into the maternal blood. - 3-5% of pregnancies result in preeclampsia.

Question 36

How is preeclampsia treated?

Answer 36

Preeclampsia is treated by removing the placenta.

Question 37

List 5 signs of preeclampsia.

Answer 37

1 - Hypertension. 2 - Proteinuria. 3 - Headache. 4 - HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). 5 - Eclampsia (seizures).

Question 38

List List 5 risk factors for preeclampsia.

Answer 38

1 - Family history of preeclampsia. 2 - Increased interpregnancy interval. 3 - Multiple gestation (triplets > twins > singletons). 4 - Maternal age of > 40 years. 5 - Diabetes. 6 - Obesity.

Question 39

Describe the pathogenesis of preeclampsia.

Answer 39

Abnormal placentation: - In the placenta: 1 - Abnormal trophoblast invasion. 2 - Reduced trophoblast differentiation. 3 - Altered trophoblast secretions. 4 - Enhances trophoblast apoptosis. 5 - Increased fibrin deposition. - Effect on the mother: 1 - Systemic endothelial activation. 2 - Systemic inflammatory response.

Question 40

What is placenta previa? What causes it? What are the risks of placenta previa?

Answer 40

- Placenta previa is blockage of the cervix by the placenta. - It is caused by implantation of the blastocyst high on the posterior wall of the uterus. - Placenta previa increases the risk of haemorrhage and placental abruption (bleeding of the placenta).

Question 41

What is placenta accreta? What causes it? What are the risks of placenta accreta? How is placenta accreta treated?

Answer 41

- Placenta accreta is inseparable integration of the placenta in the uterus. - It is caused by excessive trophoblast invasion into the decidua, reaching the underlying myometrium. - Placenta accreta increases risk of maternal haemorrhage. - Birth must be done by C-section if there is placenta accreta, and a hysterectomy might be necessary.