11. Implantation Flashcards
Lecture learning outcomes
What are the key stages in pregnancy establishment?
Key stages of pregnancy establishment:
1) Pre-implantation development
2) Implantation
3) Signal pregnancy presence
4) Maternal recognition of pregnancy
What is the free living phase of blastocyst?
Free living phase - not implanted = pre-implantation development is in free living phase
How long is the free living phase in humans compared to toher species?
Rather short - free living phase = pre-implantation development - in humans 6 days - similar in rodents
Longer free living phase in sheep - 16 days
What are the ways in which the blastocyst/embryo is maintained?
Nutrition from the mother - two types:
- histiotrophic nutrition - nutrients secreted into uterine lumen - transfer to TE - but later on becomes inadequate as embryo grows
- haemotrophic nutrition - through maternal-fetal circulation in placenta - more efficient transfer - diffucion O2, CO2, urea, Abs, glucose
How does the uterus change with the implantation window
Uterus changes:
1) pre-receptive: mucin coat, resists attachment
2) receptive: thinning of mucin, microvilli shorten, ECM interactions
3) refractory: resistant to attachment again
Explain what is the implantation window
A time period when the uterus is receptive to emrbyo implantation
How does the embryo travel in the oviduct?
What depends on the stages when monozygotic twins arise?
The later monozygotic twins arise - the lower the degree of splitting
What are the implantation stages?
- Apposition
- Attachment
- Implantation
- Invasion
AAII
What are the molecular interactions in implantation?
In implantation:
- tethering by binding to lectin on endometrium
- heparin (EGT-like growth factor) binding on endometrium to EGF expressed by trophoblast - simulates invasion
- integrins on endometrium bind to ECM components of embryo
What single molecule best determines implantation?
Endometrial LIF expression - implantation occurs when LIF high / at its peak
Explain what is LIF
Leukemia inhibitory factor (LIF) - key implantation gene in mouse - LIF KO infertile because no implantation - LIF released from endometrium (maternal side) because LIF KO embryos transferred into WT implant
Can supplement LIF for implantation - but role in humans unclear only in mice
What are the cellular processes in invasion?
In invasion:
- Decidualisation
- Angiogenesis
- Endometrial tssue breakdown and remodelling - proteinase
- Cell-cell interactions critical to ensure amount of invasion for placentation
Explain what is decidualisation in embryo invasion
Implantation + decidualization occur together + extensive endometrial remodeling of the endometrial vasculature, during which vascular expansion through the process of angiogenesis plays a central role
Decidualization - functional and morphological changes in endometrium - form the decidual lining into which the blastocyst implants - changes include the recruitment of leukocytes + differentiation of endometrial stromal fibroblast cells (ESCs) into secretory (oedema - secretory cells) decidual stromal cells (DSCs)
Explain what is angiogenesis in embryo invasion
Angiogenesis - vascular growth - an important component of the growth and function of endometrium - vascular endothelial growth factors (VEGFs) and fibroblast growth factors (FGFs) appear to be major angiogenic factors in the female reproductive organs
Implantation in humans
What are the systems of maternal recognition of pregnancy between species?
Maternal recognition of preganancy systems:
- luteotrophic
- anti-luteolytic
- coitus initiates maintenance of CL
Explain luteotrophic mechanism of maternal recognition of pregnancy
- TE secretes chorionic gonadotrophin (human hCG) - has high morphology with LH / FSH - glycosylated for greater stability / longer half-life
- hCG binds to LH receptors LHCGR on large luteal cells of CL -> maintains further progesterone secretion by CL
Explain anti-luteolytic mechanism of maternal recognition of pregnancy
Interferon τ secreted by TE - inhibits endometrial PGF2α secretion - stops luteolysis - CL breakdown -> loss of progesterone secretion
Luteolysis induced by:
- oxytocin -> prostaglandin F2α secretion by endrometrium
- PGF2α - luteolytic hormones
Explain how coitus initiates maintenance of CL
Coitus (intercourse) initiates maintenance of CL by prolactin - stimulates prolactin surge
If only female mice housed - anovulatory - when males added synchronous ovulation - stimulated by pheromones
Pseudopregnancy initiated using sterile males - coitus will maintain CL for progesterone
Explain what is luteal - placental shift
Luteal - placental shift - when progesterone secretion by CL declines - secretion taken over by placental TE cells to maintain pregnancy
What type of maternal recognition of pregnancy is used in humans?
Luteotrophic mechanism - CL not essential throughout the whole pregnancy in women
Lecture summary
