L12: Implantation and Maternal Recognition of Pregnancy Flashcards
What are the key stages in the establishment of pregnancy?
- pre-implantation development
- implantation
- signal its presence
- maternal recognition of pregnancy (fetal ‘allograft’)
What is the free living phase of blastocyst? how long does it last?
Phase before implantation, when blastocyst exist as a free floating structure. Varies with species: short (lived free phase in human and rodent 4-6 days); longer free phase (sheep - 16 days)
What are the two main types of nutrition of blastocyst and embryo?
- histiotrophic nutrition
- haemotrophic nutrition
What is histiotrophic nutrition?
- proliferative phase of menstrual cycle is developing glands, which will be secreting into uterine lumen to support blastocyst coming down from fallopian tube
- Material secreted from glands into the uterine lumen by endometrium and transfer to trophectoderm (however, once embryo gets bigger, it becomes inadequate)
What is haemotrophic nutrition?
Once embryo gets bigger and nutrition becomes inadequate, placenta forms and haemotrophic nutrition forms - requires establishment of adjacent maternal and fetal circulations on placentra for efficient transfer:
- diffusion (O2, CO2, urea);
- endocytosis fluid uptake (large molecules eg antibodies);
- carrier based mechanisms (facilitated diffusion (eg glucose) active transport against gradient (e.g. Na/K ATPase))
What is the implantation window of the blastocyst?
Important timing in endometrium, when blastocyst can implant.
- pre-receptive - mucin coat (MUC-1 forms glycocalix, long microvilli, high surface charge) i.e. resists attachment
- receptive - thinning of mucin, microvilli shorten and low surface charge, integrin - extracellular matrix interactions
- refractory - again resistant to implantation
How is the degree of monozygotic twinning determined?
The degree of splitting is determined by the timing of the split
- DC/DA – two eggs that ovulate, result two embryos, if they split at 1-3 days after fertilization, completely separate – dichorionic diamniotic
- MC/DA – when they divide at days 4-8, end up with membrane between them, separate placentas but one chorion – monochorionic diamniotic
- MC/MA – when they divide at days 8-13 – end up with two babies in the same sack, sharing a placenta – monochorionic monoamniotic (really challenging, one takes more input from placenta, one grows faster than the other)
What are the main stages of implantation?
- Hatching: out of zona pellucida
- Apposition: adhesion molecules in the lumen, on the endometrium and embryo
- Adhesion
- Invasion: different degrees, can be dangerous, can cause damage if invades too much, often happens if had a C section before
What is the molecular dialogue for implantation? What are the molecules involved?
- complex, with redundancy, poorly understood in human, species specific
- apposition
- attachment:
i) tethering by carbohydrate - lectin (on endometrium) binding
ii) heparin binding EGF-like growth factor (endometrium) with trophoblast expressing EGF and heparan sulphate protegolcyans - stimulates invasion
iii) integrins (alpha-v beta-3 on endometrial eptihelium, binds to ECM components on embryo including fibronectin)
What is the key implantation gene in the mouse? What is the experimental evidence?
- Leukemia Inhibitory Factor (LIF)
- LIF knock out mouse model is fertile but they fail to implant
- LIF knock out blastocysts viable when transferred to wild-type recipient
- or can supplement with LIF for implantation
- transient secretion of LIF from endometrial epithelium at implantation
- promotes attachment
- promotes decidualisation
What is decidualisation?
transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunocompetent matrix indispensable for embryo implantation and placental development
What happens during invasion stage of implantation?
- decidualisation response (cells become secretory) - oedema (cytokines eg TGF-beta)
- angiogenesis
- tissue breakdown and remodelling (matrix metalloproteinases)
- cell-cell interactions are critical to ensure appropriate amount of invasion for placentation
What signal is needed for the implanting conceptus to survive?
Must signal to mother to maintain progesterone support and function of corpus luteum / corpora lutea (CL)
What are the three systems for maternal recognition of pregnancy?
- luteotrophic
- anti-luteolytic
- coitus initiates maintenance of CL
What is the luteotrophic mechanism? explain what happens
- chorionic gonadotrophin (CG) secreted by trophoblast
- gonadotrophin - high homology with LH and FSH
- glycosylated to confer greater stability / longer half-life
- binds to LH receptors on large luteal cells of corpus luteum (CL)
- maintains and further stimulates progesterone secretion
