Lecture 9 - Embryo implantation and placental development Flashcards
Implantation: when does it occur and what is the name given to blastocyst implantation through the endometrium epithelium into the endometrium stroma?
~ day 6
Interstitial implantation into the endometrium - this interstitial implantation can also happen in the fallopian tubes, incidence of this is rising!
Blastocyst development: what structures are there and how do they progress through the pregnancy?
Epiblast - forms the foetus
Primitive endoderm - forms a membrane around the foetal sac
Trophectoderm - forms the placenta
Zona pellucida: how is it broken and what does this allow to happen?
Thinned and broken by blastocyst growth pressure and enzymatic activity - exposed trophectoderm can then attach to the endometrium
Attachment phase of human blastocyst attaching
Polar region of the trophectoderm mediates attachment to the endometrial luminal epithelium
Window of implantation
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
Decidualisation: what is it, why does it occur, and what do cells that have undergone it do?
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
How are progesterone levels maintained after implantation?
Implanting embryos secrete hCG which maintains progesterone levels
hCG: what is it, what is it produced by, and what does it do?
human chorionic gandotrophin
Produced by the trophoblast
Luteotrophic action - rescues the corpus luteum and causes it to continue to produce progesterone and maintain decidualisation
hCG vs FSH/LH
Same α subunit in all three
hCG has a specific β subunit - it is a heterodimer of the α and β subunits
Implantation failure and early pregnancy loss: how frequent is it in humans and why may it occur at its frequency?
<10-20% of pregnancies have a miscarriage, higher than other animals
- High level of chromosomal abnormality of human embryos?
- Endometrial abnormalities?
How do embryos rapidly grow?
Histiotrophic nutrition - prominent glands in decidua at implantation site and deciduised stroma cells between glands
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?
‘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
Histiotrophe: what is the mechanism of converting food into a state that can be consumed by the embryo?
Decidual glycogen broken down by glycogen phosphorylase and amylase to produce a histiotrophic secretion which can be taken up by the placenta
Embryonic yolk sac: what is it and what does it do?
Membranous structure that is used as a concentrated nutrient supply for the developing embryo
Placental villi: where does they develop from, how does their development work, and what stages are there?
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
Placental villi: what types are there and what is their function?
Anchoring villi
Floating villi
Results in close proximity of foetal and maternal blood - allows nutrition to be gathered from the mother’s blood
Syncytiotrophoblasts: what are they and what do they do?
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
Cytotrophoblasts: what are they and what do they do?`
Inner layer of trophoblasts
Stem cells which can differentiate into syncytiotrophoblasts - forming a specialised multinucleated structure
Does the villi structure remain constant throughout the pregnancy
No, placenta membrane becomes a single sheet at term - higher efficiency to pass nutrient
If a single cytotrophoblast layer is the most efficient, why isn’t it just a single layer throughout the whole pregnancy?
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
Placental capillary maturation
No, the cytotrophoblast layer becomes a single sheet at term - higher efficiency to pass nutrient
Mesenchyme of placenta: what is it, what does it do, and where is it located?
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
Placental vascularisation
From 18-20 days post fert capillaries are present - defining point for tertiary villi
Placenta: what is its structure and what is its size?
- 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
Cotyledons: what are they in humans, how many are there, and what are they separated by?
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
Differences in structure between first and third trimester placentas?
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))
Core placental function: what are the three core functions, what cells are essential to all three, and why are these functions necessary?
- 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
Mechanisms of exchange: what are they and what are they used for?
- 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
Transcellular diffusion: what is it, what is it affected by, and what molecules undergo this?
The movement of material across cells passively
- Barrier thickness
- Surface area
- Solubility
- Syncytial thickness
- Vasculosyncytial membrane
O₂, CO₂, and fatty acids
Paracellular diffusion: what is it and what molecules undergo this?
The movement of hydrophilic substances through small holes between cells in the placenta
Sugars, small molecules, metabolites, etc
Transcellular facilitated diffusion: what is it, what is an example, and what protein is needed for this example?
The passive movement across cells of substances through the use of channel proteins
Glucose through the GLUT1 transporter
Transcellular active transport: what is it, what is an example, and what protein is needed for this example?
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
Transcytosis: what is it, what are the types of it, and what is an example of a molecule requiring this transport method?
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)
Syncytiotrophoblast hormone production throughout pregnancy: what hormones do they produce and what do they do?
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
PGF: what is it and what does it do?
Placental growth factor
Affects maternal physiology, promotes mobilisation of glucose stores through insulin resistance
hPL: what is it and what does it do?
Human placental lactogen
Affects maternal physiology, promotes mobilisation of glucose stores through insulin resistance
Maternal metabolic changes
Insulin resistance - less glucose converted to glycogen - glucose transfer to foetus encouraged
