Implantation Flashcards
Implantation
attachment of fertilized egg to uterine lining, which occurs about 6-7 days after fertilization. Primary processes - blastocyst hatching and decidualization
- much of our knowledge from limited pathology specimens/extrapolation from other species
- requires direct, coordinated interaction between blastocyst (specifically outer trophectoderm) and the hormonally primd lning of the uterine cavity.
Blastocyst hatching
process when blastocyst “escapes” from zona pellucida (about 6-7 days after ovulation (day 20-21 from LMP). Until now, ZP served as protective shell.
- Likely that blastocyst products activate lytic factor(s) in uterine fluid
- once hatched, trophectoderm can come into direct contact with endometrial epithelium
Decidualization
process where endometrial stromal cells, fibroblasts, are transformed into round decidual cells
- dependent on progesterone and cAMP. In humans, this process begins in secretory phase of menstural cycle vs after implantation in some species
- Predecidualization: when stromal cells immediately adjacent to spiral arteries begin to transform into rounded decidual cells. If fertilization occurs, this process expands to include remaining stromal cells
- different names depending on location of decidua
- Decidua basalis: resides under implanting embryo
- Decidua capsularis: overlies embryo and
- Decidua parietalis: covers remainder of uterine surface
Window of implantation
only a finite period of time the epithelium lining of the uterus is prepared to accept implantation of blyastocyst. This occurs at day 20-24 of menstrual cycle. Endometrium becomes more vascular and edematous and glands have enhanced secretory activity. Some infertility can be due to defects in ability to transform endometiral lining or decidualization
- During this time, pinopodes (small finger-like projections) form on the apical surface of endometrial epithelium. Dependent on progesterone and can be suppressed by estrogen.
- Pinopodes involved with endocytosis of macromolecules and uterine fluid
Corpus luteum
what remains of follicle after it has been released from ovary. Main source of progesterone.
- corpus luteum maintained by human chorionic gonadotropin (hCG) produced from trophectoderm of blastocyst
hCG
- molecule produced from trophoectoderm of blastocyst that is closely related to LH.
- Immunosuppressive properties, growth-promoting properties and is likely critical for implantation
- Beta subunit detected in OTC pregnancy kits.
Immunosuppressive factors produced by preimplantation embryo
- hCG
- early pregnancy factor (EPF)
- Platelet activation factor (PAF)
- Other growth factors as well
Most common site of implantation
- most frequently in upper posterior wall in midsagittal plane but can occur anywhere in cavity
- some OB complications based in implantation site
- If implantation near the cervix–placenta previa can occur. Can still get viable pregnancy
- If implantation over site if prior uterine scar: placeta accreta can develop. Can still get viable pregnancy
Risk factors for ectopic pregnancy
- tubal surgery (20x)
- previous ectopic (10x)
- previous salpingitis (4x)
- ART (4x)
- Age
Sites of ectopic implantation
- Ampullary segment (80%)
- Isthmic segment (12%)
- Fimbrial end (5%)
- Cornual and interstitial (2%)
- Ovarian (0.2%)
- Cervical (0.2%)
- Abdominal (1.4%)
Stages of Implantation
Apposition
Adhesion
Invasion
Apposition
First stage of implantation.
- Lose unstable connection between trophoectoderm and endometrial lining. Microvilli of trophoblast interdigitate with pinopodes
Adhesion
2nd stage of implantation
- Stronger connection created by ligand-receptor interactions. Integrins, heparin or heparin sulfate proteoglycans and receptors, and L-selectin expression by trophoblast appear to play a role
- interactions thought to lead to cytoskeletal changes in epithelial cells so they dislodge and allow access of trophoblast to basal lamina
- At this point, the asymmetric blastocyst positioned such that the inner cell mass is on the side to embed first
Integrins
cell surface receptors that bind extracellular matrix (laminin and fibronectin) and intracellular cytoskeletal components
Invasion
3rd stage of implantation
- once blastocyst adheres to epithelium and trophoblastic cells rapidly proliferate adn differentiate into syncytiotrophoblasts adn cytotrophoblasts
- Syncytiotrophoblasts extend long protrusions and secrete TNF-alpha that interferes with expression of cadherins/beta-catenin to assist with epithelial cell dislodgement.
- Also secrete autocrine factors/proteases (metallloproteinases/serine proteases)that promote invasion through basement membrane and endometrial stroma (decidua)
- Other substances thought to play a role in implantation: prostaglandins, colongy stimulating factor-1 (CSF-1), leukemia inhibitory factor (LIF) and interleukin-1 (IL-1)
