REPRO: Implantation, placentation and hormone changes in pregnancy

Question 1

What do we need for implantation to occur?

See image

Answer 1

• A fully developed endometrium.
• A receptive endometrium.

A fully developed blastocyst (about day 5/6), which is fully expanded and hatched out from the zona pellucida.
It is this mass of hatched cells which, once free from the zona pellucida, will implant into the lining of your womb and form the pregnancy. The zona pellucida (from the oocyte) is a protective protein coating that surrounds the cell membrane (inherited from oocyte). The trophoblast surrounds the embryoblast and blastocoel. The trophoblast gives rise to the placenta.

The embryoblast (inner cell mass (ICM)) gives rise to the foetus. The position where the ICM is concentrated is known as the embryonic pole and the opposite end is the abembryonic pole. The blastocoel is the fluid filled cavity. Hatching occurs from the abembryonic pole.

A receptive endometrium (in the secretory phase of the menstrual cycle) with a thickened lining. The expression of the the embryo receptivity markers is also needed for the fully hatched blastocyst to interact with.

Question 2

What are trophoblasts?

Answer 2

They are cells of the blastocyte that invade the endometrium and myometrium (day 5-6). They secrete βhCG (human chorionic gonadotrophin).

Question 3

What are the chorion and the amnion?

Answer 3

The chorion is that which becomes the placenta.

The amnion is the layer that becomes the amniotic sac.

Question 4

What sequentially happens during the early stages of pregnancy?

Answer 4

• there is differentiation of the trophoblast
• trophoblastic invasion occurs, of the decidua and the myometrium
• remodelling of the maternal vasculature in the uteroplacental circulation
• development of the vasculature within the trophoblast.

Question 5

What are the stages of implantation and how long is the window of implantation??

Answer 5

1. Apposition - the position of the blastocyst where its in the right confirmation and ready to attach to the uterus (endometrium.)
2. Attachment - where the blastocyst attaches to the endometrium.
3. Invasion - where the blastocyst burrows into the endometrium and implants itself.

It is between 24-36 hours, between Day 5-6.

Question 6

Briefly describe what happens after fertilisation (from day 1 to day 5) and what happens to the blastocyst?

Answer 6

fertilisation –> pro-nuclei form –> pro nuclei fuse together (day 1) –> cell division –> two cell state (day 2) –> four cell state –> eight cell state (day 3 to 4) –> blastocyst forms at day 5.

The blastocyst bathes in uterine fluid and then begins to hatch around the end of day 5. After full blastocyst expansion the zona pellucida becomes a lot thinner and hatching is achieved via a combination of mechanisms: (1) Enzymes that dissolve the zona at the abembryonic pole (2) A series of rhythmic expansions and contractions that enable the blastocyst herniate and bulge out of the zona pellucida. The blastocyte cells that invade the endometrium and myometrium (trophoblasts).

Question 7

Describe the implantation timeline from day 7 to day 12.

Answer 7

Day 7-8: Blastocyst attaches itself to the surface of the endometrial wall (decidua basalis).

Trophoblast cells start to assemble to form a Syncytiotrophoblast in order facilitate invasion of the decidua basalis.

Day 9-11: Syncytiotrophoblast further invades the decidua basalis and by Day 11 its almost completely buried in the decidua.

Day 12: Decidual reaction occurs. High levels of progesterone result in the enlargement and coating of the decidual cells in glycogen and lipid-rich fluid.

This fluid is taken up by the Syncytiotrophoblast and helps to sustain the blastocyst early on before the placenta is formed. A syncytium is a fusion of multiple cells to form a multinucleated cell mass.

Question 8

Describe βhCG.

Answer 8

It is the hormone known as the ‘maternal recognition of pregnancy’. It’s maximal at 9-11 weeks, and is the basis of urinary pregnancy tests (testing for the β subunit).

Serum βhCG (quantitative) is useful for monitoring early pregnancy complications, eg. ectopic pregnancies, miscarriages, etc.

It helps with the maintenance of the corpus luteum, thus maintaining progesterone production.

Question 9

What is decidualisation?

Answer 9

Decidualisation - process resulting in significant changes to cells of the endometrium in preparation for, and during, pregnancy.

In humans, it happens before fertilisation even occurs.
Decidualisation happens under progesterone, so it is vital that it keeps getting released until placental steroidogenesis is established.

Question 10

Describe the implantation timeline around day 14.

Answer 10

Cells of the Syncytiotrophoblast start to protrude out to form tree-like structures known as Primary Villi, which are then formed all around the blastocyst.

Decidual cells between the primary villi begin to clear out, leaving behind spaces known as Lacunae.

Maternal arteries and veins start to grow into the decidua basalis. These blood vessels merge with the lacunae – arteries filling the lacunae with oxygenated blood and the veins returning deoxygenated blood into the maternal circulation.

Blood-filled lacunae merge into a single large pool of blood connected to multiple arteries and veins. This is known as the Junctional Zone.

Junctional Zone - the the circulatory foundation for the formation of the placenta.

Question 11

What can implantation disorders cause?

Answer 11

Implantation disorders include ectopic pregnancy and recurrent miscarriage.

Question 12

Describe the placenta timeline around day 17.

Answer 12

Around day 17, foetal mesoderm cells start to form blood vessels within the villi – a basic network of arteries, veins and capillaries. Capillaries connect with blood vessels in the umbilical cord (formed around week 5).

Villi grows larger in size, develops into the Chorionic Frondosum.

At this point, endothelial cell wall and Syncytiotrophoblast (villi) lining separate maternal and foetal red blood cells.

On ultrasound, chorionic cavity shows up as a large dark space. Used to identify a pregnancy even before a foetus can be seen.

Question 13

What happens to the placenta in the 4th and 5th months of pregnancy?

Answer 13

In the 4th and 5th months of pregnancy, decidual septa form as they divide the placenta into 15-20 regions known as Cotyledons.

Numerous maternal spiral arteries supply blood to each cotyledon, facilitating the maternal-foetal exchange.

Question 14

Describe the maternal-foetal exchange in the placenta.

Answer 14

Takes up:

• Oxygen and glucose.
• Immunoglobulin
• Hormones
• Toxins (in some cases)

Drops:

• CO2
• Waste Products.

The placenta is typically formed in the upper uterus.
Umbilical cord typically contains 2 arteries and 1 vein.

Question 15

What are some functions of the placenta?

Answer 15

• Provision of maternal O2, CHO, amino acids, vitamins, antibodies.
• Metabolism e.g. synthesis of glycogen

Endocrine secretion e.g. hCG, oestrogens, progesterone, HPL, cortisol

• Removal of foetal waste products including CO2, urea, NH4, minerals
• Acts as a barrier against, for example, bacteria, viruses, drugs, etc.

Question 16

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

Answer 16

• A huge maternal uterine blood supply, comes in at a low pressure.
• A huge surface area in contact with maternal blood allowing for a huge reserve in function.
• Highly adapted and efficient transfer system

Question 17

What is the function of the amniotic cavity?

Answer 17

• homeostasis: temperature, fluid, ions
• vital for the development of certain structures: eg. limbs, lungs
• protection: physical, and act as a barrier, eg. ascending infection

Question 18

What is pre-eclampsia and what are some of its risk factors?

Answer 18

Its primary cause is still unclear, but it is
characterised by the narrowing of the maternal spiral arteries supplying blood to the placenta.

• 3-4% of pregnancies.
• ≥20 weeks gestation (up to 6 weeks after delivery).
• Results in placental insufficiency – inadequate maternal blood flow to the placenta during pregnancy.
• Causes new onset maternal hypertension and proteinuria.
• Symptoms range from mild to life-threatening.

RISK FACTORS:

• First pregnancy
• Multiple gestation
• Maternal age >35yo
• Hypertension
• Diabetes
• Obesity
• Family history of pre-eclampsia

Pre-elampsia + seizures = eclampsia

Question 19

What happens in Pre-eclampsia?

Answer 19

In response to the reduced blood supply, the placenta produces pro inflammatory proteins which go to the mothers circulation and disrupt endothelial cell function. This causes vasoconstriction. It also causes the kidneys to retain more salt (due to reduced blood supply). These two effects lead to causing hypertension.

Reduced blood flow to kidneys –> glomerular damage –> proteinuria.

It can also cause seizures due to distorted blood supply to the brain (because of vasoconstriction and blood pressure)

Question 20

What is placental abruption and what are some of the associated risk factors?

Answer 20

Premature separation of all or part of the placenta. Caused by the degeneration of maternal arteries supplying blood to the placenta. Degenerated vessels rupture causing haemorrhage and separation of the placenta.

Symptoms include vaginal bleeding and pain in the back and abdomen

RISK FACTORS:

• Blunt force trauma e.g. car crash, fall
• Smoking and recreational drug use – risk of vasoconstriction and increased blood pressure.
• Multiple gestation
• Maternal age >35yo
• Previous placental abruption

Question 21

What are the maternal and foetal complications associated with placental abruption?

Answer 21

MATERNAL COMPLICATIONS:

• Hypovolemic shock (causing multiple organ failure as not enough blood being supplied)
• Sheehan Syndrome (Perinatal Pituitary Necrosis) –> shrinking of anterior pituitary and loss of secondary characteristics
• Renal failure –> loss of blood supply
• Disseminated Intravascular Coagulation (from release of thromboplastin) –> formation of blood clots

FOETAL COMPLICATIONS:

• Intrauterine hypoxia and asphyxia
• Premature birth.

Question 22

What is placental previa and what are some of the associated risk factors?

Answer 22

Placenta implants in lower uterus, fully or partially covering the internal cervical openings. The cause is still unclear. It could be due to the endometrium in the upper uterus not being well vascularised.

Associated with increased chances of pre-term birth and foetal hypoxia.

RISK FACTORS

• Previous caesarean delivery
• Previous uterine/endometrial surgery
• Uterine fibroids
• Previous placenta previa
• Smoking and recreational drug use
• Multiple gestation
• Maternal age >35yo

Question 23

Describe the hormonal changes after implantation?

Answer 23

After implantation, cells from the foetal placenta (trophoblasts) produce hCG. hCG binds to the LH receptor on the corpus luteum leading to the production of Oestrogen (smaller quantity) and Progesterone (bigger quantity.) This low to high oestrogen:progesterone ratio is required to main a pregnancy.

Question 24

When does the placenta take over hormonal control in pregnancy and what does it synthesise?

See diagram’s’

Answer 24

Placenta takes over around week 7. It synthesises oestrogens from foetal androgens from the foetal adrenal cortex.

It also synthesises progesterone from maternal cholesterol.

It also produces Human Placental Lactogen (hPL) which downregulates maternal insulin so there is more glucose availble for both mother and foetus. When gone wrong this can cause gestational diabetes. HPL may also have a role in lactation.

Question 25

Describe the actions of progesterone, with regards to hormonal changes in pregnancy.

Answer 25

Placental steroidogenesis takes place at about 7-8 weeks. It produces progesterone.

Rise in progesterone causes:

• mood changes
• nausea and taste changes
• loosened ligaments
• breast changes
• darkened skin (nipple)

It is thought that progesterone is responsible for decidualisation (with the corpus luteum). It is also involved in smooth muscle relaxation (uterine quiescence) and breast development. It also has a mineralocorticoid effect (cardiovascular changes).

Question 26

Describe the actions of oestrogen, with regards to hormonal changes in pregnancy.

Answer 26

Oestrogens (E1, E2, E3) rely on androgns coming from the foetus and maternal glands.

They are responsible for:

• increase blood volume
• shallow breathing
• increased urinary output

SS Flashcards:

• the development of uterine hypertrophy
• metabolic changes (insulin resistance)
• cardiovascular changes
• breast development

Question 27

Glossary

See summary slides.

Answer 27

Blastocyst: An embryo at a stage of development characterised by cells forming an outer trophoblast (trophectoderm) layer, an embryoblast (inner cell mass) and a blastocoel (fluid-filled cavity). The trophoblast layer gives rise to the placenta while the embryoblast layer gives rise to the foetus.

Endometrium: The outer mucous membrane lining the uterus, which thickens during the menstrual cycle in preparation for possible implantation of a blastocyst.

Decidua: Modified endometrium that is formed in response to progesterone, in preparation for pregnancy. Modification process is known as decidualisation.

Placenta – A large organ that is formed during pregnancy, connecting maternal and foetal blood circulation. The placenta facilitates maternal-foetal exchange which is crucial for sustaining foetal development.

Human Chorionic Gonadotrophin (hCG): A hormone produced by the placenta after implantation and an indicator of a successful pregnancy. Urine pregnancy tests are based on hCG detection.