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M6112 > L4: Intercellular communications during implantation > Flashcards

L4: Intercellular communications during implantation Flashcards

1
Q

What are the crucial requirements for embryo implantation?

A
  • Window of implantation (days 19 - 21)
  • Healthy embryo at blastocyst
  • Receptive endometerium -> effective communication between mother and embryo at time of implantation)
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2
Q

Define infertility:

A
  • Unable to get pregnant after 1 year of unprotected sex
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3
Q

Incidence of infertility in UK:

A
  • 1 in 6 couples
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4
Q

In ART, what is the proportion of failure due to implantation failure?

A
  • 70%
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5
Q

What are the three key stages of embryo implantation?

A
  • (Hatching)
  • Apposition
  • Adhesion (tissues express adhesion molecule, pinopodes)
  • Invasion (of endometrial stroma by trophectoderm layer of blastocyst)
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6
Q

Effect of estrogen in endometrial stroma:

A
  • Oestrogen induces expression of…
  • IL-11 -> Promotion of decidualisation (alongside activin A)
  • IGF1
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7
Q

Role of HB-EGF in endometrial stroma:

A
  • Promotes glandular secretion
  • Endometrial cellular proliferation
  • Decidualisation
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8
Q

Role of TGFB on embryo competence:

A
  • Increases invasiveness
  • Promotes adhesion of trophobast
  • Promotes pre- and post-implantation embryo development
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9
Q

Role of TGFB in uterine receptivity:

A
  • Promotes proliferation
  • Decidualisation
  • Promotes implantation
  • Remodelling of endometrium
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10
Q

Effect of COX-2 expression by blastocyst on endometrium:

A
  • Catalyses prostaglandin production (E)
  • -> Increased vascular permeability
  • -> Promotes implantation
  • -> Promotes adhesiveness of uterine lining (endometrium)
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11
Q

Endocrine: What factors do ovarian estrogen and progesterone affect:

A
  • GFs -> proliferation
  • TFs -> Transcriptional programmes
  • Lipid mediators -> tissue interactions
  • Cytokines -> Immune response
  • Cell cycle regulators -> quality control, cell death
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12
Q

How does estrogen and progesterone communicate with the cell?

A
  • Via estrogen receptors (alpha and beta) or PR-A, -B
  • Expressed in epithelium and stroma of human endometrium
  • ER: Interaction with site-specific DNA and coregulatory proteins
  • PR: activation regulates transcriptional programmes for implantation
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13
Q

Outline the modes of effect of hCG in the early embryo:

A
  • Secreted by early embryo, commonly found in women’s blood and urine throughout pregnancy (testing)
  • Autocrine effect on trophoblast
  • Paracrine effect on maternal ovary and endometrium
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14
Q

Outline the communication by cytokines in early embryo:

A
  • IL-1 system: IL-1alpha and -beta, 2x receptors (type I, II), receptor antagonist
  • Act as first line of response of blastocysts to a receptive endometrium -> induces second wave of cytokines/GFs
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15
Q

Communication by IGFs in receptive endometrium:

A
  • System: 2x ligands, 2x receptors, 6 BPs
  • IGFBP-1 modulates mitogenic and metabolic effects of IGF1, 2
  • Localised to predecidual stromal cells in late secretory-phase endometrium and decidual cells during pregnancy
  • IGF2: Secreted by trophoblasts, inhibits IGFBP-1 (negative feedback)
  • IL-1B: Inhibits IGFBP-1
    -> Clarify!
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16
Q

MUC-1 and its role:

A
  • Highly polymorphic mucin-like protein
  • Acts as a barrier to implantation -> removed prior to implantation
17
Q

Osteopontin and its role:

A
  • Upregulated in receptive endometrium
  • Strongly upregulated by progesterone in mid-secretory, receptive phase
  • Various forms
  • Binds to cell surface receptors, signals through adhesion proteins and coreceptors (IGF1R, EGFR, FGRF)
18
Q

Define extracellular vesicles:

A
  • Membrane enclosed nano-sized vesicle discharge by a cell that carries cargo between cell
  • Cargoes: DNA, RNA, proteins
19
Q

What are the three classes of EV?

A
  • Apoptotic bodies
  • Microvesicles
  • Exosomes
20
Q

How do EVs act in tumours?

A
  • Carrying CS marker, signalling molecules, oncogenic proteins, nucleic acids -> horizontal transfer to target cells
  • Conditioning microenvironment to support tumour growth
21
Q

Cardiovascular function of EVs:

A
  • Maintaining normal cardiac function
  • Released by cardiomyocytes
  • Also contribute to cardiovascular disease
22
Q

EVs in implantation:

A
  • Secreted by both trophectoderm and endometrium (ideal case)
  • Involved in processes across all stages of process
  • Key method for paracrine signalling (e.g. quality control of blastocyst)
  • e.g. hCG, IL-1B secretion by embryo
23
Q

Evidence for quality control via EVs (bovine oviductal epithelial cells):

A
  • EVs released by individually cultured pre-implantation embryos can alter gene expression in BOECs
  • Transcriptional response of BOECs varied by embryo quality
  • -> Potential for quality sensing role in vivo
  • -> Applications in non-invasive quality assessment in clinics

M6112 (15 decks)

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