MCDB 240: Implantation and Infertility

Question 1

describe implantation

Answer 1

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.

Question 2

there are multiple steps to implantation: what are the main three?

Answer 2

1) apposition: growth of successive layers of cell wall
2) adhesion
3) implantation

each step mediated by specific ligands and cell adhesion molecules

Question 3

why is there a low or high degree of failure for implantation?

Answer 3

there is a high rate of failure at implantation b/c there is a need for selection, w/ only the best embryos attaching

Question 4

what is the structure of the endometrium?

Answer 4

surface layer
glands
vessels
stroma

Question 5

define infertility and its causes

Answer 5

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)

Question 6

define receptivity

Answer 6

ability of embryo to implant

Question 7

how are multiple implantations prevented?

Answer 7

only 1 egg ovulutes

Question 8

define synchronization

Answer 8

window of time when embryo developing at right rate and matches up w/ receptive endometrium, there is a SMALL window of time

Question 9

define two types of uterine defects dealing w/ receptivity and synchronization

Answer 9

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

Question 10

describe the implantation cascade

Answer 10

1) blastocyst attaches to mucins on endometrial surface (w/ help of fibronectin-TUN)
2) adhesion molecules allow trophoblast to attach to endometrium (integrin)

Question 11

where are the endometrial marker present?

Answer 11

some at beginning of menstraul cycle, some at end

Question 12

define the endometrial function test

Answer 12

panel of endometrial markers based on cascade will yield add’l info about developmental stages of stroma and glands

Question 13

define the proliferation and differentiation in the menstrual cycle

Answer 13

• proliferation and differentiation can’t occur at same time (unless cancer)
• regulated by HPO axis

Question 14

describe the HPO axis and the components in the regulation of the menstrual cycle

Answer 14

• gonadotropins
• estrogen: proliferation (too much - uterine lining turns cancerous)
• progesterone: differentiation
• gene regulators: HoxA10
• cytokines: EGF, TGF, LIF, IL-1, IGF-1
• cyclins

Question 15

describe the mitotic cycle

Answer 15

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

Question 16

describe the role of cyclin E and p27

Answer 16

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

Question 17

how were the roles of cyclin E and p27 found?

Answer 17

via routine endometrial biopsy, and immunochemistry, using formalin-fixed, paraffin-embedded material

Question 18

describe the presence of cyclin E and p27, where are they in which parts?

Answer 18

cyclin E present in proliferative stage, and p27 in differentiating stage

Question 19

describe the endometrial function test: how is it done, particularly for cyclin E?

Answer 19

• 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

Question 20

define glandular developmental arrest

Answer 20

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)

Question 21

recall the case study: what were some results from it?

Answer 21

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

Question 22

define endometriosis

Answer 22

endometrium that is shed can’t leave cervix for some reason and starts growing in PELVIS, leads to inflammation and disturbance of mentstraul cycle