W6 - Implantation, placentation and hormone changes in pregnancy Flashcards
What do we need for implantation to occur?
A blastocyst is an embryo at the stage ready for implantation - 5/6 days after implantation. The inner cell mass gives rise to the embryo. The surrounding cells called the Trophoblast gives rise to the placenta. There is also a fluid filled cavity called the blastocoel. The space where the inner cell mass is concentrated is called the inner embryonic pole, the opposite end is the abembryonic pole.
- Fully expanded
- Hatched out from the zona pellucida - without hatching, implantation cannot occur. The zona pellucida getting thinner as the blastocyst forms. Digestive enzymes digest the zona to assist with the hatching process. The blastocyst then senses that and undergoes a series of rhythmic expansions and contractions to enable it to be herniated out of that area that’s being digested. It knows not to digest the zona at the embryonic pole.
We also need a receptive endometrium.
- Thickened endometrial lining.
- Expression of embryo receptivity markers.
What are the stages of implantation?
- Apposition - the positioning of the blastocyst in a confirmation where it’s ready to attach to the uterus. It’s the positioning of the blastocyst close to the endometrium.
2.Attachment - the blastocyst attaches to the endometrium.
3.Invasion - the blastocyst burrows into the ednometrium and implants itself.
What is the implantation timeline?
Days 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.
Syncytium is a fusion of multiple cells to form a multinucleated cell mass. As the Trophoblast cells start to die off, we have more being added to it. So this is a continuous process that helps the invasion.
Days 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.
This is a remodelling of the cells in response to the invading blastocysts part driven by progesterone.
From menstruation, we have high levels of progesterone being produced from the corpus luteum, that progesterone drives this process in response to the entry of the blastocyst.
The decidual cells start to enlarge and they start to become coated with fluid that’s rich in carbohydrates and lipids. This fluid is then taken up by the blastocyst and sustains it before the placenta is formed and before the placenta takes over that function. Glucose and glycogen is important for the early stage.
What happens on Day 14?
- 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. These spaces are usually filled with uterine secretions. - 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. This is the point that makes the end of the implantation process and the beginning of the placenta formation.
What happens in the placenta?
The formation of the placenta is a combination effort from the mother and the foetus.
* 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.
In the 4TH & 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.
What happens in The Placenta in terms of- maternal↔foetal exchange
Through the placenta, the foetus takes up:
- O2 and Glucose
- Immunoglobulins
- Hormones
- Toxins (in some cases)
Drops off:
- CO2
- Waste products
Within the umbilical chord, there is typically 2 arteries and 1 vein.
What are the functions of the placenta?
Provision of maternal O2, CHO, fats, amino acids, vitamins, minerals, antibodies.
Metabolism e.g. synthesis of glycogen.
Barrier e.g. bacteria, viruses, drugs etc.
Removal of foetal waste products e.g. CO2, urea, NH4, minerals.
Endocrine secretion e.g. hCG, oestrogens, progesterone, HPL, cortisol.
Why is the placenta good at it’s job?
Huge maternal uterine blood supply – low pressure.
Huge surface area in contact with maternal blood.
Huge reserve in function.
What is Pre-eclampsia?
PRE-ECLAMPSIA
* Primary cause is still unclear.
* 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 - drastic spike in blood pressure.
- Proteinuria - foamy appearance in urine.
- Symptoms range from mild to life-threatening.
Pre-eclampsia is followed by seizures = Eclampsia
What are the risk factors?
First pregnancy
Multiple gestation
Maternal age >35yo
Hypertension
Diabetes
Obesity
Family history of pre-eclampsia
What influences Pre-eclampsia?
When there is a reduced blood supply, the placenta produces pro-inflammatory proteins that makes their way into the mother’s circulation. These pro-inflammatory proteins disrupts endothelial cell disfunction.
This leads to vasoconstriction, which starts to affect other organ systems.
In the case of proteinuria, due to the reduced blood supply to the kidneys, this hampers the Glomerulus filtration system that occurs in the kidney. The kidney then starts to retain more salt because of the reduced blood supply - causes a retention of fluid. This leads to increased blood pressure. The vasoconstriction along with fluid retention leads to the new onset of hypertension. Also, with proteinuria, the filtration system is insufficient. Proteins that normally doesn’t go through will go through - start seeing them in urine.
With seizures, the vasoconstriction revolves in blood flow at a higher pressure to the brain - severely affects brain activity. This is where the seizures come from.
What is Placental Abruption?
Premature separation of all or part of the placenta.
Symptoms include vaginal bleeding and pain in the back and abdomen.
- Caused by the degeneration of maternal arteries supplying blood to the placenta. Degeneration goes onto a point where the vessels rupture causing haemorrhage and separation of the placenta.
RISK FACTORS
Blunt force trauma e.g. car crash, fall
Smoking & recreational drug use – risk of vasoconstriction and increased blood pressure.
Multiple gestation
Maternal age >35yo
Previous placental abruption
What are some maternal and foetal complications from Placental Abruption?
COMPLICATIONS – MATERNAL
* Hypovolemic shock - a lot of blood would have been lost because of haemorrhaging. There then isn’t enough blood to pump to the organ systems. This leads to multiple organ failure.
- Sheehan Syndrome (Perinatal Pituitary Necrosis)- if there is not enough blood supply to the brain, there will be shinking and necrosis of the anterior pituitary. This means you start to see a loss of secondary sexual characteristics.
- Renal failure - loss of blood supplies to the kidneys.
- Disseminated Intravascular Coagulation (from
release of thromboplastin)- would see a widespread release of thromboplastin. This results in blood clots all throughout the circulation.
COMPLICATIONS – FOETAL
* Intrauterine hypoxia and asphyxia - loss of blood supply.
* Premature birth
What is Placenta Previa?
- Placenta implants in lower uterus, fully or partially covering the internal cervical os. Usually, the implantation occurs in the upper uterus, this means the baby is delivered before the placenta.
- Associated with increased chances of pre-term birth and foetal hypoxia.
Cause still unclear.
? Endometrium in the upper uterus not well vascularised?
RISK FACTORS
Previous caesarean delivery
Previous uterine/endometrial surgery
Uterine fibroids
Previous placenta previa
Smoking & recreational drug use
Multiple gestation
Maternal age >35yo
What are hormonal changes in pregnancy?
Once implantation has occured, cells from the foetal placenta produces HcG. Since HcG has LH-like properties, it is able to bind to the LH receptor on the corpus luteum. Resulting in the production of estrogen (E) and progesterone (P) from the corpus luteum. Estrogen is produced in a low E:P ratio. This is necessary for maintaining a pregnancy.
Around week 7, the placenta takes over and this correlated with a HcG drop. The placenta continues to produce E and P. Also, there is a production of Human Placental Lactogen (hPL). It counteracts the effects of maternal insulin so there is a lot more glucose available for the mother and the foetus. There’s times this can go wrong where the mother could end up more resistant to insulin (gestational diabetes), disappears after birth.
How does Progesterone and Estrogen get made?
Mother provides Cholesterol + LDL to the placenta.
Placenta converts it to Pregnenolone -> Progesterone
In the Adrenal Glands of the foetus, DHEA-S is being produced. This gets converted to Estrone, Estriol and Estradiol.
HPL is also part of the placental output.
