W5L1 Mon embryo implantation Flashcards
What is implantation
-sequence of events by which the embryo attaches to the uterine surface initiates, and invades into the endometrium via implantation
What is placentation
development of the placenta
CONSEQUENCES OF ABNORMAL IMPLANTATION
- Failure to implant (due to endometrial / embryonic defects) — Infertility (affecting 1: 6 couples)
- Implantation in other regions of uterus — placenta praevia leads to premature delivery due to early separation of the placenta
- Implantation in the fallopian tube — ectopic tubal pregnancy, rupture of the fallopian tube – can be lethal
Step in the implantation and placentation process
- Apposition: blastocyst comes into close contact w/ luminal epithelium + can still be dislodged, ICM faces uterine wall
- Adhesion: connections established b/w embryo + endometrial epithelium, initiates implantation
- Invasion: trophectoderm cells intrude b/w endometrium cells (altered junctional membrane)
- Invasion through decidualised stroma to form placenta
Requirement for successful implantation
- Hatched blastocyst/embryo
- Receptive endometrium (prepared for implantation)
- Synchrony of development of endometrium and blastocyst
- Signals/Communication
- between blastocyst and endometrium
- between different endometrial cells
- Continuing maternal progesterone
Menstrual Cycle stages and implantation
§ Proliferative phase: following ovulation, ↑oestrogen results in proliferation of endometrium
§ Secretory phase: endometrium differentiates, stroma terminally differentiate (decidualisation)
Ø Mid-secretory phase when endometrium is receptive = embryo implants
Ø No implantation = CL regresses due to progesterone decrease + endometrium sheds
Endometrial Cell Types
§ Endometrium composed of epithelial cells, stromal cells, vascular cells + glandular cells
§ Function (proliferation, growth + differentiation) is regulated by growth factors, cytokines + hormones (progesterone)
§ Immune cells recruited (recruitment regulated by chemokines) from peripheral blood + differentiate within endometrium tissue
§ Redundancy in their functions to optimise receptivity of the endometrium
what is Receptivity
period of time in menstrual cycle where endometrium accepts an implanting blastocyst (day 19-23)
Ø Luminal epithelium expresses adhesion molecules to allow embryo to adhere
Endometrial changes in epithelium during receptivity
Luminal epithelium (LE): point of first contact with blastocyst at time of implantation
* altered adhesion molecules and integrity/tightness of junctions between cells, mucins, adherens, junction proteins, selectins
* less polarized to allow blastocyst attachment and invasion
Glandular epithelium (GE): become highly secretory
* Secreted epithelial factors such as cytokines, MMPs, proteases enter into a communication with blastocysts
Decidualization
Morphological and biochemical differentiation of human endometrial stromal into decidualized endometrial stromal cells (pre-dedidual cells) and occurs in the secretory phase of the menstrual cycle.
If implantation occurs, they are called decidual cells
Problem of abnormal decidualisation
Abnormal decidualization results in infertility, miscarriage, intrauterine growth restriction, preeclampsia
Decidualisation features
- Progesterone dependent
- Involves reprograming of many cell functions
- Altered steroid hormone receptor expression – high Progesterone R
- Remodelling of extracellular matrix and cytoskeleton
- Regulators include: Intra-cellular enzymes
- Growth factors
- Cytokines and their receptors
- Transcription factors
- Apoptosis modulators
Endometrial leukocytes
§ Endometrial leukocytes (WBCs) composition changes from proliferative to mid-secretory phase
Ø Largest changes seen in uterine natural killer + macrophage numbers
Ø During 1st trimester: uNK 70% of leukocytes + macrophages 20% of leukocytes
Regulation of decidualization: role of
immune cells
Immune cells are recruited from peripheral blood by chemokines produced by vascular cells in endometrium
Ø Decidual cells release factors that regulate immune cells + how they differentiate
Ø Immune cells also regulate decidual cells
Uterine specific natural killer (NK) cells: Role in decidualization
Uterine specific: express cell surface antigen CD56 bright (10% peripheral blood NK cells)
* Actions regulated by activating and inhibitory receptors
* Produce cytokines ie. CSF, TNFα, IFNγ, TGFβ
* High abundance in mid-late secretory phase human endometrium and decidual of pregnancy
* Involvement in initiation of decidualization in humans
NK deficient mice : implantation occurs suggesting differences between mice and humans
