MCDB 240: Implantation and Infertility Flashcards
describe implantation
b/t 5-7 days past ovulation, blastocyst begins to interact w/ endometrial surface epithelium
-trophectodermal trophoblasts firmly attach to endometerial surface, trophoblasts begin to invade epithelial layer into endometrial stroma.
there are multiple steps to implantation: what are the main three?
1) apposition: growth of successive layers of cell wall
2) adhesion
3) implantation
each step mediated by specific ligands and cell adhesion molecules
why is there a low or high degree of failure for implantation?
there is a high rate of failure at implantation b/c there is a need for selection, w/ only the best embryos attaching
what is the structure of the endometrium?
surface layer
glands
vessels
stroma
define infertility and its causes
a year of attempted pregnancy (15% in population), 50-50 male/female caused
causes: male or female don’t produce viable gametes (rare)
- more common: embryo attaches to lining of uterus, failure is there (septum in uterus, benign tumor in smooth muscle lining)
define receptivity
ability of embryo to implant
how are multiple implantations prevented?
only 1 egg ovulutes
define synchronization
window of time when embryo developing at right rate and matches up w/ receptive endometrium, there is a SMALL window of time
define two types of uterine defects dealing w/ receptivity and synchronization
unreceptive endometrium is not receptive at time blastocyst is capable of attracting to endometrial surface
type I: window is delayed, shifted to latter part of cycle
type II: endometrium is NEVER receptive, NO window
describe the implantation cascade
1) blastocyst attaches to mucins on endometrial surface (w/ help of fibronectin-TUN)
2) adhesion molecules allow trophoblast to attach to endometrium (integrin)
where are the endometrial marker present?
some at beginning of menstraul cycle, some at end
define the endometrial function test
panel of endometrial markers based on cascade will yield add’l info about developmental stages of stroma and glands
define the proliferation and differentiation in the menstrual cycle
- proliferation and differentiation can’t occur at same time (unless cancer)
- regulated by HPO axis
describe the HPO axis and the components in the regulation of the menstrual cycle
- gonadotropins
- estrogen: proliferation (too much - uterine lining turns cancerous)
- progesterone: differentiation
- gene regulators: HoxA10
- cytokines: EGF, TGF, LIF, IL-1, IGF-1
- cyclins
describe the mitotic cycle
proliferation phase: functional layer of endometrium goes thru repeated mitotic cycles every month
luteal phase: cells stop dividing and differentiate
cyclins mediate said phases/processes, provide checkpoints
describe the role of cyclin E and p27
cyclin E binds CDK2, allows G1 phase to progress to S phase
p27 binds cyclin E and stops process from going back to the S phase for the cell
how were the roles of cyclin E and p27 found?
via routine endometrial biopsy, and immunochemistry, using formalin-fixed, paraffin-embedded material
describe the presence of cyclin E and p27, where are they in which parts?
cyclin E present in proliferative stage, and p27 in differentiating stage
describe the endometrial function test: how is it done, particularly for cyclin E?
- use needle to get piece of endometrial tissue, examined under microscope
- test of cyclin E in tissue
- use immunochemistry to bind primary antibody to cyclin E (provides color)
- cyclin E present from beginning of menstrual cycle until day 18/19
- p27 takes over for latter part of cycle
-biopsy at day 15 and 29 to see cycle pattern, slope of progesterone especially important
define glandular developmental arrest
in infertile women, cyclin E presisted through entire menstrual cycle (all proliferation, no differentiation, so endometrium isn’t progressing)
women expressed cyclins into differentiation stage (infertile)
recall the case study: what were some results from it?
case study showed that when stressed, it could lead to ireegular menstrual cycles, so taking some time off could push back glandular developmental arrest
-when EFT repeated, endometrium normal and NO cyclin E in second half
define endometriosis
endometrium that is shed can’t leave cervix for some reason and starts growing in PELVIS, leads to inflammation and disturbance of mentstraul cycle
