Implantation (wk 3) Flashcards
What are the 6 names of the stages of implantation?
Transport Orientation Hatching Apposition Attachment Invasion
Why is implantation necesssary?
Uterine secretions bathe the blastocyst (provides oxygen and metabolites necessary for growth/survival)
Important for the blastocyst to generate its own blood supply
What are the two main requirements for implantation?
Involves SYNCHRONISATION between the blastocyst and uterine wall
Uterine wall needs to become receptive and the blastocyst needs to acquire implantation competancy
Relies one ovarian hormones (estrogen and progesterone) and locally produced signalling molecules
What are the three stages of receptivity of the uterus to blastocyst?
Pre-receptive phase
- Epithelium has long apical microvillis, thick glycocalyx, negative charge
- impairs attachment
Receptive phase
- Apical protusions absorb volume and decrease volume in the uterine cavity
- Loss of negative charge
- Microvilli shorten, glycocalyx thins
- Attachment is ready
Refractory phase
- Goes back to a structure similar to pre-receptive phase
- Resists attachment
T/F: during the pre-receptive phase, the uterine wall has a positive charge
False: negative charge
T/F: the terminal web disappears during the receptive phase
True
T/F: the focal adhesions remain during the receptive phase
False: they disappear to enable implantation
Where do oestrogen and progesterone come from?
The ovaries
T/F: oestrogen and progesterone levels are low during the pre-receptive phase
True
Describe the levels of oestrogen and progesterone during the receptive phase
Elevated
Their peaks are critical to drive the receptive phase
Describe the glandular epithelium during the pre-receptive phase
Increases in secretory function
Drives the epithelial mesenchyme transition
Are tight junctions lost or kept during uterine receptivity?
Lost
What happens to the glycocalyx proteins during uterine receptivity?
Uterus and embryo secrete enzymes to cause post-translational modifications
(chop them up)
What is the role of focal adhesions?
Provide a structural link between the ECM and cytoskeleton
Explain the role of osteopontin in terms of blastocyst adhesion competancy
Ovary secretes oestrogen
Then uterus secretes osteopontin
Osteopontin binds to integrin receptors on blastocyst which makes them activated and they aggregate together
Assists the blastocyst for adherance
Explain the role of oestrogen in terms of endometrium receptivity
Oestrogen is secreted by ovary and acts on uterus
Endometrial glands secrete LIF (leukaemia inhibitory factor)
LIF receptors are on the epithelium and stroma
Makes endometrium receptive to attachment
Explain the role of EGF
Blastocyst secretes a factor that acts on epithelial cells of the uterus
Uterus epithelial cells secrete and express heparin binding RGF
EGF has autocrine functions on blastocyst and uterus
Helps with the hatching process
List the funcitons of the zona pellucida during early pregnancy
Prevents polyspermy
Prevents premature implantation
Prevents two zygotes from sticking together
Keeps blastomeres together until compaction
Describe the two hatching mechanisms of the ZP
Rupture:
Mechanical= increase in cell numbers, ZP stretches and thins due to the pressure
Chemical= blastocyst secretes proteases to form a hole in ZP
Escape:
Embryo expands and contracts the cavity (pulsing movements), escapes through the hole in ZP
Which cells become quite close to the endometrium
Trophoblast
Close apposition and adherance of trophoblast cells to endometrium
What role do uterodomes play?
Involved in initial attachment
Flatten down when the blastocyst is brought onto the endothelial cells
Proteins on the surface of the uterodomes interact with the blastocyst
Explain how integrins and ECM proteins play a role during cel-cell attachment
Integrins on uterus and blastocyst bind to ECM proteins and use it as a glud
List some methods used for studying implantation
Co culture Multilayer culture Migration assay Transwell migration assay Invasion assay Multilayer invasion assay
Describe the stages of implantation
First: cell-cell contact (attachment)
Second: invasion by trophoblast cells through the epithelium and basement membrane
Third: decidualisation of stromal cells (so blood can come into close contact with the embryo)
What is the major cause of IVF failure?
Implantation failure
At what developmental stage is the embryo delivered back to the woman during IVF?
Blastocyst stage
T/F: during TVF, the ovaries are stimulated to produce one egg
False
They are stimulated to produce multiple eggs
How can the ZP be hatched during IVF?
Make a small hole
Thin the ZP by shining a laser
Use pippetes to squirt chemical reagents to break down ZP
Crucial for implantation
T/F: serum is aded to culture during IVF
False
no serum, simple medium maternal growth factors are absent
large volume of fluid means the autocrine growth factors are diluted
What is the difference between low and high density in IVF
Low density= one embryo, large volume of fluid, growth factors are diluted, poor development
High density= groups of embryos, small volume of fluid, growth factors are more concentrated, improved development, increased hatching
Does the addition of IGF1 assist blastocyst development during IVF?
Yes
Inhibits apoptosis, stimulates hatching, helps development, increased attachment and invasion
What is the main mechanism that allows addition of IGF1 assist attachment during IVF?
It increases the amounts of fibronectin (ECM protein)
This allows the integrins to bind to the ECM as a glue, critical for attachment process
