Lecture 9 - Embryo implantation and placental development

Question 1

Implantation: when does it occur and what is the name given to blastocyst implantation through the endometrium epithelium into the endometrium stroma?

Answer 1

~ day 6

Interstitial implantation into the endometrium - this interstitial implantation can also happen in the fallopian tubes, incidence of this is rising!

Question 2

Blastocyst development: what structures are there and how do they progress through the pregnancy?

Answer 2

Epiblast - forms the foetus
Primitive endoderm - forms a membrane around the foetal sac
Trophectoderm - forms the placenta

Question 3

Zona pellucida: how is it broken and what does this allow to happen?

Answer 3

Thinned and broken by blastocyst growth pressure and enzymatic activity - exposed trophectoderm can then attach to the endometrium

Question 4

Attachment phase of human blastocyst attaching

Answer 4

Polar region of the trophectoderm mediates attachment to the endometrial luminal epithelium

Question 5

Window of implantation

Answer 5

By the time the blastocyst is mature, it should reach the endometrium which has developed due to progesterone and estrogen signalling

Lack of implantation - progesterone withdrawal

Question 6

Decidualisation: what is it, why does it occur, and what do cells that have undergone it do?

Answer 6

The enlarging and transformation of stromal fibroblasts to form decidual cells

Occurs as a response to progesterone and inflammatory signals during implantation (ie prostaglandin E2)

Aid pregnancy:
* Control immune microenvironment
* permissive environment for gestation

Question 7

How are progesterone levels maintained after implantation?

Answer 7

Implanting embryos secrete hCG which maintains progesterone levels

Question 8

hCG: what is it, what is it produced by, and what does it do?

Answer 8

human chorionic gandotrophin

Produced by the trophoblast

Luteotrophic action - rescues the corpus luteum and causes it to continue to produce progesterone and maintain decidualisation

Question 9

hCG vs FSH/LH

Answer 9

Same α subunit in all three

hCG has a specific β subunit - it is a heterodimer of the α and β subunits

Question 10

Implantation failure and early pregnancy loss: how frequent is it in humans and why may it occur at its frequency?

Answer 10

<10-20% of pregnancies have a miscarriage, higher than other animals

• High level of chromosomal abnormality of human embryos?
• Endometrial abnormalities?

Question 11

How do embryos rapidly grow?

Answer 11

Histiotrophic nutrition - prominent glands in decidua at implantation site and deciduised stroma cells between glands

Question 12

Histiotrophe: what is it, what is it composed of, for roughly how long is it used to sustain the embryo, and what is its pathway to the embryo?

Answer 12

‘Tissue food’ (‘Uterine milk’) that feeds early embryos

Contains glucose oligomers and glycoprotein - provides nutrient supply to the embryo in early pregnancy

~11 weeks

Histiotrophe taken up by the trophoblast, then by the coelomic cavity, and then the yolk sac

Question 13

Histiotrophe: what is the mechanism of converting food into a state that can be consumed by the embryo?

Answer 13

Decidual glycogen broken down by glycogen phosphorylase and amylase to produce a histiotrophic secretion which can be taken up by the placenta

Question 14

Embryonic yolk sac: what is it and what does it do?

Answer 14

Membranous structure that is used as a concentrated nutrient supply for the developing embryo

Question 15

Placental villi: where does they develop from, how does their development work, and what stages are there?

Answer 15

Trophoblast from trophectoderm

Invade endometrium then form villi

~10 days post fert (primary villous stage) - cytotrophoblast protrusion (cytoplasm protrusion)
~12 days post fert (secondary villous stage) - extra-embryonic mesoderm incursion and branching and increased surface area
~20 days post fert (tertiaryvillous stage) - vascularisation

Question 16

Placental villi: what types are there and what is their function?

Answer 16

Anchoring villi
Floating villi

Results in close proximity of foetal and maternal blood - allows nutrition to be gathered from the mother’s blood

Question 17

Syncytiotrophoblasts: what are they and what do they do?

Answer 17

Outer layer of trophoblasts, not mitotically active

• Facilitate an environment for the exchange of substances between mother and foetus
• Provide an immunological barrier
• Produce hormones - hCG, oestrogen, progesterone, hPL, PGF, lectin, etc

Question 18

Cytotrophoblasts: what are they and what do they do?`

Answer 18

Inner layer of trophoblasts

Stem cells which can differentiate into syncytiotrophoblasts - forming a specialised multinucleated structure

Question 19

Does the villi structure remain constant throughout the pregnancy

Answer 19

No, placenta membrane becomes a single sheet at term - higher efficiency to pass nutrient

Question 20

If a single cytotrophoblast layer is the most efficient, why isn’t it just a single layer throughout the whole pregnancy?

Answer 20

Not sustainable - it is essentially killing itself as a single layer, this works, though as it reaches the end of its life as the foetus is almost ready to be born, not required for much longer

Question 21

Placental capillary maturation

Answer 21

No, the cytotrophoblast layer becomes a single sheet at term - higher efficiency to pass nutrient

Question 22

Mesenchyme of placenta: what is it, what does it do, and where is it located?

Answer 22

Placental mesenchymal (multipotent) stem cells which have a variety of uses

• ECM forming
• Fibroblast differentiation and proliferation
• Vasculature generation
• Macrophage differentiation and proliferation

Central part of villi

Question 23

Placental vascularisation

Answer 23

From 18-20 days post fert capillaries are present - defining point for tertiary villi

Question 24

Placenta: what is its structure and what is its size?

Answer 24

• Discoid
• Typically the largest structure throughout pregnancy - not the case at term as the baby rapidly puts on weight
• ~20-25cm in diameter, 3cm thick, and 400-750g

Question 25

Cotyledons: what are they in humans, how many are there, and what are they separated by?

Answer 25

The name given to the separations of the placenta which contain foetal blood and allow for transport of material between both organisms ~15-25 in humans and they are separated by placenta septa

Question 26

Differences in structure between first and third trimester placentas?

Answer 26

1ˢᵗ trimester: * Continuous cytotrophoblast layer * Extensive proliferation and fusion to form syncytiotrophoblasts * Vasculature growth begins 3ʳᵈ trimester: * Reduced villi diameter * Thinning of cytotrophoblast (50-100µm - 4-5µm) - now only covering ~20% of villi diameter * Highly vascularised * Vasculosyncytial membranes (single layer protecting the bloods from mixing (and subsequent foetal death))

Question 27

Core placental function: what are the three core functions, what cells are essential to all three, and why are these functions necessary?

Answer 27

* Protective barrier * Nutrient supply and material exchange * Hormone production and secretion Syncytiotrophoblasts are critical for these three functions * Barrier from immune system of mother, toxins, drugs, and pathogens * Waste expulsion to prevent build-up of waste material as well as nutrients to supply for growth * Endocrine tissue to allow for adaptation to maternal physiology

Question 28

Mechanisms of exchange: what are they and what are they used for?

Answer 28

* Transcellular diffusion - O₂, CO₂, fatty acids, etc * Paracellular diffusion - hydrophilic substances * Transcellular facilitated diffusion - glucose, etc * Transcellular active transport - amino acids, etc * Transcytosis - random/bound substances

Question 29

Transcellular diffusion: what is it, what is it affected by, and what molecules undergo this?

Answer 29

The movement of material across cells passively * Barrier thickness * Surface area * Solubility * Syncytial thickness * Vasculosyncytial membrane O₂, CO₂, and fatty acids

Question 30

Paracellular diffusion: what is it and what molecules undergo this?

Answer 30

The movement of hydrophilic substances through small holes between cells in the placenta Sugars, small molecules, metabolites, etc

Question 31

Transcellular facilitated diffusion: what is it, what is an example, and what protein is needed for this example?

Answer 31

The passive movement across cells of substances through the use of channel proteins Glucose through the GLUT1 transporter

Question 32

Transcellular active transport: what is it, what is an example, and what protein is needed for this example?

Answer 32

The energy-driven movement of substances across cells through the use of transporter proteins Amino acids System A amino acid transporter - undergoes a symport mechanism to transport neutrally charged amino acids by also using sodium ions

Question 33

Transcytosis: what is it, what are the types of it, and what is an example of a molecule requiring this transport method?

Answer 33

The uptake of the plasma membrane for transportation across the cell * Receptor-mediated - molecule binds to a receptor, then transported (Igs, Transferrin, etc) * Receptor-independent - random sampling of the environment near the plasma membrane (small molecules, proteins, etc)

Question 34

Syncytiotrophoblast hormone production throughout pregnancy: what hormones do they produce and what do they do?

Answer 34

hCG produced initially - causes corpus luteum survival, continuing progesterone production Oestrogen and progesterone produced after around 16 weeks of pregnancy - keeps placenta built up until term hPL - Starts to slowly rise over the weeks of pregnancy, affects maternal physiology, promotes mobilisation of glucose stores through insulin resistance PGF - Starts to slowly rise over the weeks of pregnancy, affects maternal physiology, promotes mobilisation of glucose stores through insulin resistance

Question 35

PGF: what is it and what does it do?

Answer 35

Placental growth factor Affects maternal physiology, promotes mobilisation of glucose stores through insulin resistance

Question 36

hPL: what is it and what does it do?

Answer 36

Human placental lactogen Affects maternal physiology, promotes mobilisation of glucose stores through insulin resistance

Question 37

Maternal metabolic changes

Answer 37

Insulin resistance - less glucose converted to glycogen - glucose transfer to foetus encouraged