L11 - The Placenta Flashcards

1
Q

In which phase of the menstrual cycle does a blastocyst implant into the endometrium?

A
  • The blastocyst implants into the endometrium in the mid-luteal phase, when oestrogen and progesterone are high
  • The implantation window is day 19-24 of menstruation
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2
Q

What are pinopodes?

What is their function?

A
  • Pinopodes are the structures formed by the swellings of the endometrium surface, which is normally covered with cilia
  • Pinopodes function to trap the blastocyst into the endometrium, as they replace the cilia that normally beat the blastocyst across the endometrium
  • They are indicative of the implantation window
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3
Q

Give a chronological overview of the events preceding implantation, starting from fertilisation.

A
  • Day 0: Fertilisation occurs at the ampulla
  • Day 1-3: The first, second and third cleavages occur to produce an 8-cell uncompacted morula
  • Day 4: An 8-cell compacted morula forms
  • Day 5: The early blastocyst forms, consisting of an inner cell mass, a blastocoel (fluid-filled cavity) and trophectoderm (the precursor to the placenta that provides nourishment)
  • Day 6-7: Zona hatching occurs and the zona pellucida degenerates
  • Day 8-9: The blastocyst implants into the endometrium
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4
Q

Describe the process of blastocyst implantation into the endometrium.

A

1 - Apposition - initial loose association of the blastocyst with the uterine wall

2 - Attachment - subsequent firm adhesion of the blastocyst to the uterine wall

3 - Invasion - the blastocyst initiates enzyme production to degrade and invade the glycogen-rich endometrium, providing further nutrient support

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5
Q

What is decidualisation?

A
  • Decidualisation is the process by which the endometrium undergoes morphological and biochemical changes in preparation for implantation
  • It is induced by progesterone
  • It is marked by:

1 - Oedema

2 - Changes in the extracellular matrix

3 - Vascular remodelling

4 - Uterine natural killer cell infiltration

5 - Glycogen and lipid uptake

6 - Secretion of decidual proteins

7 - Transformation of fibroblast-like cells to secretory epithelial cells

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6
Q

What is the function of uterine natural killer cells?

A
  • Uterine natural killer cells infiltrate the endometrium in preparation for implantation to prevent an autoimmune response against the blastocyst
  • There are no T cells at the site of implantation
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7
Q

How does the syncytiotrophoblast form?

A

The syncytiotrophoblast forms as a result of fusion of villous cytotrophoblasts

*The syncytiotrophoblast doesn’t completely replace the villous cytotrophoblasts - they both exist in the developing embryo

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8
Q

Describe the structure of the placenta.

A

Placenta microstructure:

  • The placenta is split into many lobes, each contained within syncytiotrophoblastic shells
  • Within the lobes are many chorionic villi, which lie in a pool of maternal blood in intervillous spaces. They are the site of exchange between maternal and foetal blood and are formed of villous cytotrophoblastic cells
  • The intervillous spaces are supplied with maternal blood by the endometrial spiral arteries and endometrial veins. The blood crosses the syncytiotrophoblast shell to reach the chorionic villi

Placenta gross structure in relation to the amniotic sac:

  • The placenta surrounds the amniotic sac
  • The amniotic sac is separated from the placenta by the amniochorionic membrane, which is composed of an outer chorion (part of the placenta) and an inner amnion (part of the amniotic sac)
  • The vessels of the chorionic villi fuse at the chorion to form the umbilical cord, which projects towards the embryo in the amniotic sac
  • The amniotic sac receives nutrients from the foetal circulation, which derives nutrients from the chorionic villi
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9
Q

Why is the human placenta considered to be haemochoroidal?

A

The human placenta is considered to be haemochorodial because the chorion is in direct contact with maternal blood

*This is best because it offers the shortest diffusion distance

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10
Q

How does the blastocyst derive nutrients before the formation of the placenta?

A
  • Before placenta formation, the blastocyst derives nutrients and oxygen by diffusion from the surrounding decidua in which it is implanted
  • This is known as histiotrophic nutrition
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11
Q

Describe the development of placental villi.

A
  • In early placental formation, the syncytiotrophoblast invades and erodes maternal capillaries
  • Separate pores then form in the syncytiotrophoblast, known as lacunae
  • The lacunae anastomose with the maternal vessels, forming sinusoids, which eventually form the intervillous spaces
  • The cytotrophoblasts invade the syncytiotrophoblast to form finger-like projections between the sinusoids. These structures are the primary chorionic villi
  • Extraembryonic mesoderm from the inner cell mass invades the core of the primary villi. The primary villi are now secondary chorionic villi
  • The mesoderm differentiates to form endothelial cells, which fuse with the band of mesoderm known as the embryonic stalk (later the umbilical cord) to link the foetal blood system to the maternal blood system. The secondary villi are now tertiary chorionic villi
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12
Q

How does the microstructure of the tertiary chorionic villi of the placenta change over time as the placenta matures?

A
  • The mature chorionic villi form stem villi, which are the basal villi attached to the chorion
  • Branch villi project from the sides of stem villi
  • Terminal villi are the swellings at the tips of branch villi. They are the sites where most exchange takes place
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13
Q

How does the extravillous trophoblast form?

A

Cytotrophoblasts at the end of the anchoring villi proliferate and differentiate to form the extravillous trophoblast

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14
Q

What are the functions of extravillous trophoblasts?

A

1 - Extravillous trophoblasts remodel spiral arteries in preparation for pregnancy

2 - Extravillous trophoblasts communicate with uterine natural killer cells to establish immune tolerance to the blastocyst

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15
Q

Why and how do spiral arteries remodel during embryo development?

A
  • First trimester: EVT differentiate at tips of anchoring villi -> from cytotrophoblasts to interstitial & endovascular EVT
  • EVT invade decidua & occlude spiral aa. -> reduce blood flow to developing placenta -> prevents intervillous space from filling w/ highly oxygenated maternal blood -> low O2 environment & protects foetus from oxidative stress
  • EVT cells also replace endothelium & SM of spiral aa. -> low resistance, high flow BVs -> diameter increases 10-fold => remodelling initiated/promoted by uNK cytokines
  • EVTs lay down fibrous CT matrix to act as rigid funnel
  • Cells from middle repopulate wall -> non-thrombogenic endothelium
  • No vasoregulation in placenta -> not influenced by mother
  • EVT plugs remain throughout histotrophic phase of pregnancy until wks 12-14 -> plug breaks down -> blood flow into intervillous space
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16
Q

What are the maternal adaptations to meet the increasing O2/nutrient demand of the growing foetus?

A
  • Uterine bloodflow increases 20-fold during pregnancy via uterine (+ ovarian) aa.
  • CO increases by 30-40% -> greater %CO to ovarian/uterine aa. (ca 25% CO)
  • Increased maternal BV & ventilation rate
17
Q

How is glucose absorbed by the foetus?

A
  • Uptake via insulin-insensitive hexose transporters GLUT1 & GLUT3
  • Maternal insulin regulates glucose -> increases glycogen & adipose stores
  • Maternal tissues show insulin insensitivity/resistance due to hPL -> promote transfer of blood glucose to placenta
  • Glucose metabolised to lactate = foetal energy source
18
Q

How are amino acids absorbed by the foetus?

A
  • Foetus regulates maternal amino acid metabolism through progesterone
  • Mother able to retain extra AAs & transport them into foetal circulation via active transport; some metabolised
19
Q

How is foetal urea excreted?

A

Passively diffuses into maternal blood

20
Q

Which tissue of the placenta forms the primary barrier to nutrients?

A

Syncytiotrophoblast

21
Q

Which antibody is transferred from the maternal blood to the foetus?

How is it transferred?

A
  • IgG

- Via pinocytosis

22
Q

What is IUGR?

What causes it?

A
  • Intra-uterine growth restriction (IUGR) / early-onset pre-eclampsia
  • Due to insufficient penetration by EVT into spiral aa.
23
Q

What are the effects of poor remodelling of the spiral arteries on the foetus and blood flow to the chorionc villi?

A

High pressure flow -> vasoconstriction – pulsatile flow -> ischaemia/reperfusion injury/oxidative stress -> villi damage

24
Q

What are the signs of pre-eclampsia?

A

HTN, proteinuria, headache, HELLP (haemolysis, elevated LFTs, low platelets), DIC, seizures (eclampsia)

25
Q

Describe the pathogenesis of pre-eclampsia.

A
  • Abnormal trophoblast invasion, ↓ differentiation & transport, altered trophoblast secretions, enhanced trophoblast apoptosis, & ↑fibrin deposits
  • Lead to systemic endothelial activation & maternal systemic inflammatory response
  • Inflammatory cytokines bind VEGF in kidneys -> prevents formation of fenestrations -> glomerular damage -> proteinuria
26
Q

What is placenta previa?

A
  • Blastocysts usually implant high on post uterine wall, so cervix not obstructed -> assoc w/ myometrial scarring from previous C-section
  • Placenta praevia classified on degree of coverage of cervix -> increased risk placental abruption/haemorrhage
27
Q

What is placenta accreta?

A
  • Excessive trophoblast invasion of endometrium -> invades & becomes inseparable from uterine wall -> identified by US
  • Vaginal bleeding 3rd trimester -> risk maternal haemorrhage
  • Assoc w/ placenta praevia
  • Requires pre-term C-section or hysterectomy