Molecular aspects of implantation Flashcards
Structure of the endometrium?
Glandular and luminal epithelium
Stromal cells
Blood vessels
Proliferative phase
Small glands with overlapping epi cells
Dense stroma
Early secretory phase
Glands expand, secretory vesicles at basal side of epithelial cells
Mid secretory phase
Increase expansion of glands
Secretory vescles secrete into lumen
Late secretory phase
Long extended glands, no secretory vesc
Oedema in stroma
What is present in the secretory vesicles?
Factors that interact with the embryo and facil implantation
What drives endometrial changes?>
Steriod hormones
O - growth of endo
P - secretion of material by endo, drives WOI
Where/when are steroid R expressed?
In nuc of stromal and epi cells
PR: max in early secretory phase then decrease
ER: max in late prolif/early secretory phase
What leukocytes are present in endo?
uNK, macro, T cells (no B cells)
Increase in uNK and leuko from prolif to early preg
How is cycle timed?
- From last menstrual period
- LH surge (LH+7 - implant)
3, Endo morph
Abnorm endo function
- RIF - due to abnorm endo - no implant
2. RM - due to abnorm placental form - implant successfully
What do the Tb do during implantation
Villous TB; anchor and invade cap/endo/stroma
Endogland/vasc: invade glands/vasc
ScTB: Forms barrier between tropho and maternal
What is decidualisation controlled by?
cAMP and progesterone
MMPs
Pro form cleaved by trypsin or plasmin to activate
b.d. pt in endo
MMP9 - early/late menstruation
Prog - decreased MMP exp
IL1 and TNFa - increase MMP exp
TB cells exp MMP to b.d. endo at implantation
Integrins
Mediate cell binding to ECM
Transduce signal from ECM to cells
Endo integ - avB3, a1, a4 upreg at WOI
Integrins at WOi
Inc exp in epi and BV
avB3 - exp in luminal and gland epi equally
a1 and a4 - high exp in gland epi and BV
Integrins and repro failure
Abnorm expression
What cytokines are expressed in endo?
Pro inflam - IL1, TNFa, IFNy, LIF, IL6, IL11
Th1 and Th2 cytokines
TGFb, GM-CSF, CSF, IL12, IL18, IL15
Where are cyto exp after implantation?
Decidua and epithelium
Role of LIF?
KO mice = no implant, model of infertility
Decreased exp in gland epi of women with RIF
Role of IL11?
KO of R = implant but small decidua = loss
KO = model of RM
Decreased endo exp of IL11 in women with RM
Do trophoblast cells express cytokine r?
Yes, cytokines can have positive or negative effects on TB cells
Endometrial transcriptomes
Compare g.e. at different points in cycle and different pathologies. Can identify specific g.e. associated with receptivity
