Implantation, placentation, and hormone changes in pregnancy

Question 1

What do we need for implantation to occur?

Answer 1

1) A fully developed blastocyst

You have two definitive cell lines, the embryoblast, which gives rise to the baby, and the surrounding cells which are the trophoblast, which gives rise to the placenta. You also have a fluid filled cavity called the blastocoel. For implantation to occur we need the blastocyst to be fully expanded and to be hatched out from the zona pellucida.

2) A receptive endometrium

This would have thickened during the secretory phase, and it is expressing receptivity markers to communicate with the blastocyst at this stage.

Question 2

Summarise the stages of implantation?

Answer 2

1) Apposition
The close positioning of the blastocyst to the uterine wall/endometrium

2) Attachment
The cells of the trophoblast attach the blastocyst to the endometrium

3) Invasion
The trophoblast cells multiply and invade into the endometrium and completely bury the embryo and implant it into the endometrium

Question 3

What happens on days 7-8 of implantation?

Answer 3

• The blastocyst attaches itself to the surface of the endometrial wall (known as the decidua basalis)
• The trophoblast cells start to assemble and form a Syncytiotrophoblast (a group of multi-nucleated trophoblast cells). It is basically an endless supply of cells, so as syncytiotrophoblasts die off - the ones in contact with the endometrium - more start to form and join the Syncytiotrophoblast.

Question 4

What happens on days 9-11 of implantation?

Answer 4

The Syncytiotrophoblast further invades the decidua basalis and by day 11 it is almost completely buried in the decidua

Question 5

What happens on day 12 of implantation?

Answer 5

The decidual reaction occurs - high levels of progesterone due to the luteal phase triggers the decidual reaction.

The cells that make up the endometrial wall (decidua) start to enlarge and become coated in fluid that is sugar and lipid rich. What this does is it serves as a source of nutrition for the blastocyst. The cells of the Syncytiotrophoblast take up these nutrients (the glycogen and the sugars), which sustains the blastocyst before the placenta takes over

Question 6

What happens on day 14 of implantation?

Answer 6

• Cells of Syncytiotrophoblasts start to form tree-like structures called primary villi, which are formed all around the blastocyst
• In response to the presence of these villi, we decidual cells begin to clear out, leaving behind empty spaces known as Lacunae
• The maternal arteries start to grow into the Desidua from the mother’s size. They fill these spaces with oxygenated blood. These blood filled spaces will merge into a single pool of blood. All of this is known as the Junctional Zone. The junctional zone is the circulatory foundation for the formation of the placenta.

Question 7

What are some functions of the placenta?

Answer 7

1. Steroidogenesis - oestrogens, progesterone, HPL, cortisol
2. Provision of maternal O2, CHO, fats, amino acids, vitamins, minerals, antibodies, etc.
3. Removal of CO2, urea, NH4, minerals
4. Acts as a barrier against, for example, bacteria, viruses, drugs, etc.

Question 8

How is the placenta adapted to be good at its job?

Answer 8

• a huge maternal uterine blood supply, at low pressure
• a huge reserve of function
• a huge surface area in contact with maternal blood
• highly adapted and efficient transfer system

Question 9

What happens in the maternal-foetal exchange?

Answer 9

The placenta in this exchange takes up:

• O2 and glucose
• Immunoglobins
• Hormones
• Toxins

Drops off:

• CO2
• Waste products

It is important for you to know that the umbilical cord is usually made up of two arteries and one vein.

Question 10

What is pre-eclampsia?

Answer 10

A condition in pregnant woman whereby women who have not had high blood pressure before develop it.

It results in placental insuffiency, which is inadequate blood supply to the placenta from the mother.

Question 11

What are some risk factors for pre-eclampsia?

Answer 11

• Patients going through their first pregnancy
• Women undergoing multiple gestations (twins, triplets)
• Increased maternal age (>35 yo)
• Hypertension
• Diabetes
• Obesity
• Family history of pre-eclampsia

Question 12

What are the symptoms of pre-eclampsia?

Answer 12

Main symptoms are new maternal hypertension (high blood pressure which shows up during the pregnancy), and proteinuria (presence of protein in the urine due to the glomerular damage).

The symptoms range from mild to life threatening. For example, if the pre-eclampsia is accompanied by seizures, it results in eclampsia, and at this point is a medical emergency. The seizures are due to the eventual damage that would occur to other body systems as a result of the maternal hypertension and the degeneration of the spiral arteries.

Question 13

What causes pre-eclampsia?

Answer 13

The primary cause of eclampsia is still unclear, but we know it is characterised by narrowing of the maternal spiral arteries.

In normal pregnancy, the spiral arteries that supply the placenta dilate to allow more blood flow, but in pre-eclampsia they are usually fibrous and they narrow, which limits blood supply. As a result the placenta responds to this by secreting pro-inflammatory proteins, which make their way into the maternal circulation and cause dysfunction of endothelial cells. This will cause a domino affect and affect body systems a result. The initial signs you would see are the proteinuria and the hypertension, because of the link between blood pressure and kidney disorders. Eventually, these will go on to affect other body systems, which is where the seizures come from.

Question 14

List the chain of events that arises from the endothelial cell dysfunction?

Answer 14

1) Vasoconstriction, which affects the arteries that supply the kidney, as well as the capillaries around the glomerulus
2) This causes glomerular damage, causing proteinuria
3) Vasoconstriction would also cause hypertension

Question 15

What is placental abruption?

Answer 15

This is premature separation of all or part of the placenta from the endometrium.

Question 16

What are the risk factors for placental abruption?

Answer 16

• Blunt force trauma (fall/car crash)
• Smoking and recreational drug use - risk of vasoconstriction and increased blood pressure
• Multiple gestation
• Maternal age >35 yo
• Previous placental abruption
• Hypertension from severe pre-eclampsia

Question 17

What causes placental abruption?

Answer 17

This is primarily caused by the degeneration of the maternal arteries supply blood to the placenta. They will rupture, causing haemorrhage and separation of the placenta. Symptoms include vaginal bleeding and pain in the back and abdomen. This will become a medical emergency too.

Question 18

What are some complications of placental abruption?

Answer 18

For mother:
- Hypovolemic shock (heart does not have enough blood to circulate to organs in the body)
- Sheehan syndrome (degeneration of the pituitary gland. This is because due to the hypovolemic shock, there is not enough blood and O2 supplied to the pituitary. This causes loss of secondary sexual features, loss of pubic and axillary hair, shrinkage of the breasts, and impaired reproductive function)
- Renal failure
Disseminated intravascular coagulation (due to the rupture in the blood vessels, there is a lot of blood clotting factors released into the blood system. You start to have blood clots being formed all across the vessels in the body)

For foetus:

• Intrauterine hypoxia and asphyxia
• Premature birth

Question 19

What is placenta previa?

Answer 19

This is when the placenta implants in the lower uterus, either fully or partially covering the internal cervical opening. Associated with increased chances of pre-term birth and foetal hypoxia.

Question 20

What are the risk factors for placenta previa?

Answer 20

• Previous caesarean delivery
• Previous uterine/endometrial surgery

The rationale behind this is, when you have surgery in the uterus, those areas that have been operated on become less vascularised. When the enzyme/blastocyst is trying to communicate with the uterus and find an implantation point, it will move to the more vascularised areas of the uterus to implant. This is why we believe this happens.

• Previous placenta previa
• Uterine fibroids
• Smoking and recreational drug use
• Multiple gestation
• Maternal age >35 yo

Question 21

What happens in terms of hormones once a blastocyst is implanted?

Answer 21

The trophoblast cells start to secrete hCG and this binds to the LH receptors on the corpus luteum, resulting in the synthesis and secretion of progesterone and oestrogen.

This is produced in a low ratio necessary for maintaining pregnancy (more oestrogen than progesterone).

Question 22

What happens to the hormones once the placenta takes over?

Answer 22

At week 7 the placenta takes over, so there is a decline in hCG production due to the degeneration of the corpus luteum, but the placenta has taken over, so you see a continuous production of progesterone and oestrogen.

There is also a production of human placental lactogen (hpl).

Question 23

What does HPL do?

Answer 23

Affect the mother’s metabolism in such a way that glucose is available for both the mother and the foetus. What it does is make the mother more resistant to insulin so that there is more glucose in the bloodstream available for both the mother and the foetus.

Question 24

Where is HPL produced?

Answer 24

The placenta

Question 25

What happens if the mother does not produce HPL?

Answer 25

When HPL does not function properly, it results in gestational diabetes in the mother. This is where, during pregnancy, the mother is a bit diabetic. This is because there is severe insulin resistance in the mother, where she now becomes diabetic herself.

Question 26

How is progesterone produced from the placenta?

Answer 26

If we look at the cross talk between the foetus and the mother via the placenta, we have, in the case of progesterone, cholesterol being received from the mother, synthesised via steroidogenic enzymes, into pregnenolone and progesterone. This makes its way back into the mother’s circulation. That is in a nutshell, how most of the progesterone is produced from the placenta.

Question 27

How does the placenta produce oestrogen?

Answer 27

In the case of the oestrogens, what you have is adrenal androgens from the foetus, DHEA-S and DHEA, are converted via a series of steps into the oestrogens. The placenta converts them, and then the oestrogens make their way into the maternal circulation.

Question 28

What would a graph of hormones during pregnancy show?

Answer 28

If we look at the hormone levels during pregnancy we can see with hCG there is an initial rise, and then at week 7 it drops and declines. If we look at progesterone, oestrogen and HCL, there is a continuous rise.