molecular aspects of implantation Flashcards
what things are seen in the endometrium under the microscope?
glandular epithelium
luminal epithelium
stroma
blood vessels
what does the endometrium look like during the proliferative phase?
small glands with epithelial cells close together
dense stroma
what does the endometrium look like during the early secretory phase?
glands expanding
secretory vesicles at basal side of epithelial cells
what does the endometrium look like in the mid secretory phase?
further expansion of glands with secretory vesicles at apical side of epithelial cells
presence of secreted material in lumen
what does the endometrium look like in the late secretory phase?
long extended glands with no secretory vesicles
oedema in stroma
where are oestrogen and progesterone receptors expressed?
expressed in nuclei of stroll and epithelial cells
when is oestrogen receptor expression at maximum?
late proliferative/early secretory phase of cycle
when is progesterone receptor expression at maximum?
early secretory phase then decreases
decreases in epithelial cells before stroma
what leukocytes are present in the endometrium?
uterine natural killer cells
macrophages
T cells
(no B cells)
how do the populations of immune cells change during the menstrual cycle and early pregnancy?
uNK cells increase a lot
T cells stays same
macrophages very slight increase
what is the window of implantation?
time during which the endometrium is receptive to embryo = days 20-23
characterised by expression of specific set of factors in the endometrium
luminal epithelial cells may develop pinopod extensions
what is the initial interaction between at implantation?
trophoblast cells of embryo and luminal epithelium
later it is between trophoblast cells and stroma
what are the stages of implantation?
apposition (orientation of blastocyst on the lumen of the endometrium)
adhesion (interaction between trophoblast cells and luminal epithelial cells in endometrium)
invasion (breakdown of connective tissue between luminal epithelial cells and passage of embryo through to the underlying stroma)
what are the different populations of trophoblast cells?
villous trophoblast (invasive - come into contact with maternal stroma. anchoring) endovascular trophoblast (invade maternal blood vessels) syncytiotrophoblast (formed inside maternal blood vessels by cell fusion)
what is decidualisation?
after implantation stroma cells undergo decidualisation (change phenotype)
start secreting many factors including prolactin and IGFBP1
controlled by cAMP ad progesterone
what molecules are involved in the implantation process?
adhesion molecules = integrins and mucins
proteases
cytokines and growth factors
what are integrins?
heterodimers with alpha and beta subunits
mediate cell binding to extracellular matrix
transduce signals from ECM into cells
regulate gene expression including those of ECM degrading enzymes
unregulated in WOI
highest expression in epithelium and blood vessels
what are the different types of integrins?
αvβ3 - may be involved in attachment of embryo to endometrium
α1
α4
what are mucins and what is there role?
MUC1 = glycoprotein on lining the luminal epithelial cells
prevents embryo access to luminal epithelium
glycosylation needs to been removed to allow implantation to occur
what are matrix metalloproteinases (MMPs)?
collagenases gelatinases stromeolysins found in endometrium controlled by progesterone - decreases production therefore increased MMPs seen at end of cycle when progesterone levels decrease
what is the role of protease in endometrial function?
implantation = breakdown of extracellular matrix to allow embryo through epithelial cells, breakdown of extracellular matrix tissue to allow trophoblast cells to invade sstroma menstruation = breakdown of endometrial tissue
when does the expression of cytokine increase?
at time of implantation
what is the role of cytokines in embryo implantation?
receptors expressed by cytotrophoblast cells
shown to bring positive secretory effects and negative apoptosis and decreased cell growth of cytotrophoblast
could affect leucocyte activity (uNK)