Implantation

What happens after fertilisation?

Zygote undergoes mitotic division to increase cell no but stays same size to restores high cytoplasmic:nuclear ratio. Travel along fallopian tube facilitated by changing endocrine levels (rising ratio of progesterone:oestrogen in the luteal phase)

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What is the zygote called when it reaches the 16 cell stage & 32-64 cell stage?

16 cells: morula, undergoes compaction, maximises intercellular contacts. 32-64 cells: blastocyst, establishment of polarity of cells, generation of 2 groups of cells by asymmetric divisions into trophectoderm & inner cell mass

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How does the blastocyst form polarity of trophoectoderm?

Cells make tight and adherens junctions. E-cadherin & beta-catenin very important cell-cell adhesion molecules, provide apical/basal cell polarity. Junctional positioning transforms cell phenotype from radically symmetrical to highly polarised

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What happens during development of the blastocyst?

Asymmetrical divisions, segregation & differentiation of cells to outer cell layer called trophoectoderm (will form placenta) & inner cell mass (will form embryo), communicate via gap junctions. Formation of cavity (blastocoel)

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What are the cells in the trophoectoderm? What is their role?

Trophoblast cells: don't contribute to embryo, known as extra-embryonic cells, give rise to chorionic tissue or chorionic villi concerned with nutrition & support of embryo and foetus

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When does attachment & adherence occur?

Blastocyst attaches/adheres to endometrium in the luteal phase: saw toothed secretory glands with nutritional secretions (lipids, CHOs, nucleic acids, proteins). Trophoblast can tap into this for nutrition for continued growth and survival

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What are the 2 types of conceptus-uterus communications?

Long range (must signal its presence to mother to avoid luteal regression & loss of conceptus) and short range (must establish physical & nutritional contact) communications

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What is involved in long range conceptus-uterus communication?

Trophoblast secretes human chorionic gonadotropin (hCG), binds to LH receptors on luteal cells of the corpus luteum, this signal suppresses luteolysis & prolongs life of corpus luteum which produces progesterone to ensure further ovulation ceases

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What is involved in short range conceptus-uterus communication?

Dissolution of zona pellucida, adhesion between trophoblast & epithelial cells of endometrium -> stromal reaction, makes endometrium receptive (under progesterone control), spreads to larger area creating 3 decidual layers

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What are the 3 decidual layers?

Decidua basalis: endometrium underlying the conceptus. Decidua capsularis: superficial portion overlying the conceptus. Decidua parietalis/vera: remaining uterine mucosa. Decidualisation allows invasion/helps nutrition/protects from maternal immunity

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What happens in the endometrium during implantation?

Leukaemia inhibitory factor produced in oestrogen presence, promotes receptivity & decidualisation. Production of localised heparin binding EGF-like growth factors from epithelium adjacent to blastocyst precedes dissolution of ZP. MUC1 down regulated

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What happens during the formation of syncytiotrophoblast (ST)?

Single layer trophoblast, proliferates to cytotrophoblasts, fuse to single multinucleated tissue layer without cell boundaries, the ST. Lacks proliferative capacity, maintained by continual fusion of underlying cytotrophoblast cells throughout term

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What happens to the trophoblast layer during invasion?

Syncytiotrophoblast forms numerous finger-like projections into the endometrium. It releases proteases (including MMPs) which allows the blastocyst to burrow into the endometrium

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What happens to the endometrium during invasion?

Loosening of epithelial cells in endometrium to allow invasion. Histamine, prostaglandins, etc i.e. pro-inflammatory reaction. Tissue inhibitors can check invasion

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What happens during invasion?

Burrowing & expanding syncytial processes cause further degradation of decidual tissue. This along with secretions from uterine glands provides nutrients i.e functions as 'yolk sac reservoir', this is Histiotrophic nutrition (occurs in first 10 wks)

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What happens during lacunae formation?

Digestion of endometrial tissue forms small spaces or lacunae. Cellular debris from eroded uterine glands & maternal blood fill lacunae, providing histiotrophic nutrition. These lakes become interlinked, intervillous spaces (IVS)

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What happens during cytotrophoblast differentiation?

Some CT proliferate & fuse to form ST, project into endometrium & lacuna, branch to make free floating chorionic villi (IVS between villi). Some CT form cell columns called anchoring cells/villi or migrate out as extra-villous trophoblast (EVT)

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What is the nutritional switch in response to the growing embryo's nutritional need?

Switch from histotrophic to haemotrophic nutrition. 1st trimester: establish maternal circulation, develop chorionic villi & fetal circulation. 2/3rd: growth/branching of villi, re-modelling of feto-placental capillaries for more efficient transport

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What is haemotrophic nutrition?

Since chorionic villi lie bathed in maternal blood in intervillous spaces, nutrients and oxygen can be taken up directly from maternal blood by the chorionic villi and can diffuse into fetal blood within the fetal vessels occupying the villi

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What happens during the establishment of mono-haemochorial circulation (single layer chorionic tissue in direct contact with maternal blood)?

Lakes/lacunae develop & extends to spiral arteries. Blood from spiral arteries can now spurt straight into lacunar network. Developing chorionic villi lie in lakes and be bathed in the maternal blood. Blood drains back passively into decidual veins

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What happens during re-modelling of maternal spiral arteries by extra-villous trophoblast?

CT cells actively participate in maximising maternal blood blood. EVT invade spiral arteries, replace endothelium & smooth muscle. This ensures arteries remain open, no longer under maternal control, creating high flow/low resistance circulation

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What happens during migration of extravillous trophoblast cells?

Extravillous cytotrophoblast cells invades deep into the endometrium. During invasion there is an integrin switch on the trophoblast, switched off on attachment. Once cytotrophoblasts reach spiral arteries or even deeper, there is a switch back.

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What are primary villi?

Early in development, the chorionic villi are just CT columns covered by syncytiotrophoblast -> primary villi. These primary villi branch and elongate. They project into the maternal lacunae and float there bathed in maternal blood

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How do secondary villi develop?

The second step is the invasion of extra-embryonic mesoderm into the free primary villi, these are now called secondary villi

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How do tertiary villi develop?

The invading extra-embryonic mesoderm contains haematopoetic stem cells. These form new blood vessels which connect to each other to form a primitive capillary plexus within chorionic villi. These villi with vessels called tertiary chorionic villi

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How is placental fetal circulation established?

The fetal vessels in the chorionic villi connect with vessels of the umbilical stalk entering the chorionic plate. They are now continuous with the rest of fetal vasculature. Placental fetal blood flow begins

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Implantation

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