10-03-23 - Placentation and Implantation

Question 1

Learning outcomes

Answer 1

• 1 explain why the preimplantation embryo must act to preserve the function of the corpus luteum and what the mechanism is
• 2 describe the events that occur between fertilisation and implantation of the blastocyst
• 3 list the tissue layers that comprise the placental membrane
• 4 explain the endocrine functions of the placenta
• 5 recognise the importance of the placental membrane and be aware of what molecules and organisms are able to cross it

Question 2

When does the mother foetus link develop?

What are the 3 phases in development of the anatomical link between mother and foetus?

Answer 2

• The mother foetus link occurs early on in pregnancy
• 3 phases in development of the anatomical link between mother and foetus:

1) Invasion
* Conceptus invades endometrium

2) Decidualisation
* Endometrial remodeling including secretory transformation of the uterine glands, influx of specialised uterine natural killer cells, and vascular remodeling.

3) Placentation
* Placental formation

Question 3

Formation of the placenta.

Where is the embryonic and maternal portion of the placenta supplied by?

Where do chromonic villi extend from and to? What is vasculature of these villi like?

What is each villus surrounded by?

Answer 3

• Formation of the placenta
• The embryonic portion of placenta is supplied from outermost layers of trophoblast cells (ie the chorion).
• The maternal portion of the placenta is supplied by the endometrium (uterine tissue) underlying the chorion
• Choronic villi extend from chorion to endometrium.
• Villi have network of capillaries – part of embryo’s circulatory system.
• The endometrium around villi is changed by enzymes & paracrine agents so each villus is surrounded by a pool/sinus of maternal blood.

Question 4

Describe the flow of maternal blood in the placenta.

Describe the flow of foetal blood in the placenta.

What does the umbilical cord connect?

When does maternal and foetal blood mix?

Answer 4

• Flow of maternal blood in the placenta:
• Enters placental sinuses/pools via uterine artery
• Flows through sinuses
• Exits via uterine veins
• Flow of foetal blood in the placenta:
• Flows into capillaries of choronic villi via umbilical afteries
• Flows back to foetus via umbilical vein
• The umbilical cord connects foetus to placenta
• The blood of the foetus and mother never mix

Question 5

Summary of Events from Ovulation to Fertilisation to Implantation
* Describe the events that occur after the LH surge:
1) 1 day
2) 2 days
3) 2-4
4) 5 days
5) 6-7 days
6) 9-10 days

Answer 5

Question 6

End of Week 1 Attachment and implantation.

What occurs to the blastocyst at day 6/7?

When will attachment and implantation occur?

What happens during this period?

Answer 6

• End of Week 1 Attachment and implantation
• Day 6/7 the blastocyst leaves the zona pelucida and is bathed by uterine secretions for 2 days:

1) Progesterone prepares supportive uterine environment increasing glandular tissue

2) Oestradiol is required to release the glandular secretion

• Attachment and Implantation occurs at day 6-9 in a very limited time window
• During this period, there is complex interactions between trophoblast and maternal epithelial tissue:

1) Causes syncytiotrophoblast cells ‘flow’ into the endometrium

2) Causing oedema, glycogen synthesis and increased vascularisation (decidualisation). The pregnant endometrium is now termed the decidua.

Question 7

When does implantation occur in regards to timing for period?

What is the role of Syncytiotrophoblast cells?

What does nutrition still depend on?

What type of bleeding can occur?

How fast is growth in the embryonic disk?

Answer 7

• About the time the woman expects her next period implantation is well under way
• Syncytiotrophoblast cells erode through the walls of large maternal capillaries which then bleed into the spaces - primitive placental circulation
• Nutrition of the blastocyst still depends on uterine secretion and tissues
• Breakthrough bleeding may occur
• Growth in the embryonic disk is slow and it remains very small (0.1 - 0.2 mm)

Question 8

Placental development.

What are villi formed from?

What is located in the core of the villus?

What will then start to develop over several weeks?

Where do villi become localised?

Why is this?

When is the maternal side of placental circulation functional?

What is the nutrient and O2 supply to the first trimester embryo?

Answer 8

• Placental development
• The syncytiotrophoblast forms villi that project into the blood-filled spaces (chorionic villi).
• In the core of the villus is a fetal capillary loop - dilated at the tip (slow flow rate)
• Embryonic placental structure develops over several weeks
• The villi eventually becoming localised at the embryonic pole and presenting a huge surface area for exchange of O2, nutrients and waste products
• Maternal side of the placental circulation is restricted and is not functional until 10 – 12 weeks
• First trimester embryo mostly dependant on uterine tissues for nutrients and O2

Question 9

Chorionic villi.

What are the maternal and fetal circulations are separated by?

What does this prevent the mixing of?

What is the Syncytiotrophoblast bathed in?

Answer 9

• Chorionic villi
• Maternal and fetal circulations are separated by the placental membrane.
• There is no mixing of maternal and fetal blood
• Syncytiotrophoblast is bathed in maternal blood

Question 10

1st trimester.

How much embryo growth is there in the 1st trimester?

What can cause early pregnancy losses?

How thick does the endometrium need to be for successful implantation?

Answer 10

• 1st trimester.
• There is limited embryonic growth (complex differentiation) in the first trimester - nutrition of the embryo is mostly based on uterine secretion and tissues.
• Lack of appropriate hormonal support (luteal phase defect) may account for early pregnancy losses.
• The endometrium should be at least 8mm thick for successful implantation

Question 11

Summary of developing placenta 1

Answer 11

Question 12

Summary of developing placenta 2

Answer 12

Question 13

Describe the oestrogen and progesterone levels during the menstrual cycle (in picture).

What is the role of LH?

Answer 13

• Oestrogen and progesterone levels during the menstrual cycle (in picture)
• LH supports the steroid secretion of the corpus luteum for 10-12 days

Question 14

What is the role of hCG (Human chorionic gonadotropin).

What secretes hCG?

When is it secreted?

When does it peak?

When can it start to be measured?

Answer 14

• hCG (Human chorionic gonadotropin) maintains progesterone secretion from the corpus luteum until the placenta can synthesise its own progesterone
• Syncytiotrophoblasts secrete hCG soon after implantation (peaks ~8-10 weeks of gestation)
• HCG is measurable by day 6-7 postconception

Question 15

How soon will the corpus luteum fail after a non-fertile cycle?

What must an implanting embryo do?

How soon can hCG be detected in maternal blood?

What is the role of hCG in the corpus leteum?

What does hCG do in male fetuses?

Answer 15

• In a non-fertile cycle the CL will fail after 10 days and menstruation will occur
• An implanting embryo must prevent menstruation, so the syncytiotrophoblast secretes Human Chorionic Gonadotropin (hCG)
• From day 6-7 after fertilisation hCG can be detected in maternal blood by immunoassay (Commercial kits are sensitive enough to detect hCG in urine after ~14 days)
• hCG mimics the action of LH and supports the steroid synthesis of the corpus luteum, and therefore prevents both menstruation and any further follicular development

Question 16

When do women need progesterone?

What are 3 roles of progesterone?

When is the corpus luteum no longer required?

What is the substrate for progesterone production?

Answer 16

• Women must have progesterone for the maintenance of pregnancy - increases throughout pregnancy
• 3 roles of progesterone:
  1) Suppression of follicular growth and ovulation
  2) Suppression of the immune response
  3) Maintenance of endometrium
• After 4-5 weeks the placenta is secreting all steroid hormones required for pregnancy - CL not required after 5 weeks and the foetus is self-sufficient
• Cholesterol from the maternal circulation is the substrate for progesterone production

Question 17

What is the main oestrogen in pregnancy?

What structures cooperate to secrete oestrogens?

What are 4 roles of oestrogens?

What can measuring oestogen levels be used for?

Answer 17

• Oestriol is the main oestrogen in pregnancy
• Foetus and placenta (feto-placental unit) cooperate to secrete oestrogens (mainly oestriol)
• 4 roles of oestrogens:

1) Stimulates continuous growth of uterine myometrium (muscular layer of uterus)

2) Stimulates growth (with progesterone) of ductal tissue of breast (ducts form channels for breast milk)

3) Along with relaxin (?), relaxes and softens maternal pelvic ligaments and symphysis pubis of pelvic bones – allows expansion of uterus

4) Stimulates LDL cholesterol uptake and activity of P450 enzymes – Contribute to progesterone synthesis

• Foetal wellbeing and placental function can be measured by monitoring oestrogen levels

Question 18

What is the placenta?

Describe the growth of the placenta in the first 3 months post-conception.

What 3 systems does the placenta adopt the function of?

How large is the placental diffusion membrane?

How many molecules can pass through the placental membrane?

What can happen to syncytiotrophoblastic cells in the 3rd trimester?

Answer 18

• The placenta is an essential complex endocrine organ
• Growth of the placenta in the first 3 months post-conception:
  1) 1st month - villus formation
  2) 2nd month - increasing surface area and circulation
  3) 3rd month - growing, becoming increasingly efficient
• 3 systems does the placenta adopt the function of:
  1) GI (nutrients)
  2) Respiratory (oxygen exchange)
  3) Renal systems (removal of waste products)
• The surface area of the placental diffusion membrane is huge
• Most molecules can pass through the placental membrane - after 20 weeks placental membrane thins even more with loss of cytotrophoblast
• 3rd trimester syncytiotrophoblastic cells may be lost into the maternal blood

Question 19

Describe the diagram for placental conductivity

Answer 19

Question 20

What does the placenta consist of?

What does it serve as an organ of exchange between?

What are 4 roles of the placenta?

Answer 20

• The placenta consists of a combination of interlocking foetal and maternal tissue
• Serves as the organ of exchange between mother and foetus for remainder of pregnancy
• 4 roles of the placenta:
  1) Foetal “gut”: supplying nutrients.
  2) Foetal “lung”: exchanging O2 and CO2.
  3) Foetal “kidney”: regulates fluid volumes and disposing of waste metabolites.
  4) Endocrine gland: synthesises steroids and proteins that affect both maternal and foetal metabolism.

Question 21

How fast is nutrient exchange across the placenta?

Describe how the following substances transport across the placenta:
1) Water and electrolytes
2) Glucose
3) Amino acids
4) Lipids
5) Vitamins

How can a diabetic mother affect the birth weight of their baby?

Answer 21

• Nutrient exchange across the placenta is rapid and increases as pregnancy advances
• How the following substances transport across the placenta:

1) Water and electrolytes
* Diffuse freely

2) Glucose
* Passes via facilitated diffusion.
* Foetus has little capacity for gluconeogenesis
* Babies of diabetic mothers are heavier than normal range
* Storage of glycogen in liver for postnatal requirements

3) Amino acids
* Actively transported for fetal growth

4) Lipids
* cross as free fatty acids

5) Vitamins

Question 22

How efficient is gas exchange across the placental membrane?

How are concentration gradients influenced?

How is the quantity of O2 reaching the foetus limited?

How does foetal and adult haemoglobin differ in terms of O2 affinity?

How is exchange capacity of the placenta affected as pregnancy progresses?

Answer 22

• Simple diffusion of gases across the placental membrane is close to the efficiency of the lungs.
• Concentration gradients are influenced by blood flow rates.
• The quantity of O2 reaching the foetus is flow limited.
• Fetal haemoglobin has a greater affinity for O2 than adult haemoglobin.
• Towards end of pregnancy exchange capacity decreases and the placenta is less able to meet the demands of the foetus