Extraembryonic membranes (Smyth)

Question 1

What are the 4 extra embryonic membranes of mammals?

Answer 1

Allantois

Chorion

Amnion

Yolk sac

Question 2

What are the roles of extra embryonic membranes?

Answer 2

Transfer (store) of nutrients in and breakdown products out

Physically protect the embryo
- Protect the embryo from toxins and hormonal changes
- Protect the embryo from temperature changes
- Protect from maternal immune system

Allow growth (not pressing on the embryo)

Cellular differentiation - Gonadal stem cells (PGC),
- Haematopoietic stem cells

Drive hormonal changes-
- Signal to mother pregnancy is occurring (hCG)
- Maintain uterine relaxations and secretions (progesterone)
- End pregnancy and Induce parturition (estrogen- CRH)

Question 3

What is the role of progesterone + 17β estradiol in uterine growth and implantation?

Answer 3

Proliferative phase
- 17β estradiol
- Stimulates stromal and epithelial growth

Secretory phase:
- Progesterone + 17B estradiol
- Rich in glycoproteins sugars and amino acids
- Nurtures embryo

Question 4

What is the chorion, and how does it form in mammalian development?

Answer 4

The chorion is the first membrane to appear in embryonic development, formed from the trophectoderm

Highly motile trophoblast cells migrate from the trophectoderm into the uterine wall endometrium, forming the chorionic membrane

Question 5

How does the fetal placenta form in mammals?

Answer 5

In mammals, the fetal placenta forms from trophoblast cells in a specific region of the chorion

The allantois fuses with the chorion, and mesoderm migrates in from the embryo to form blood vessels, establishing the chorio-allantoic placenta

Question 6

How do trophoblast cells differentiate during placental development?

Answer 6

Trophoblast cells from the trophectoderm differentiate into two layers:

Inner Cytotrophoblasts serve as stem cells.

Outer Syncytiotrophoblasts form a continuous layer without cell boundaries.

Question 7

What roles do Cytotrophoblasts play later in placental development?

Answer 7

Cytotrophoblasts lining the cavity can also differentiate into:

• Trophoblstic Giant Cells help remodel maternal blood vessels.
• Spongiotrophoblasts: Involved in the structural framework of the placenta.

Question 8

What is a cytotrophoblast?

Answer 8

The cytotrophoblast is the trophoblastic stem cel

Forms four lineages
- The invasive lineage -Interstitial Cytotrophoblast
- The fusion lineage -Syncytiotrophoblast

Then later
- Through endoreduplication- TrophoblastGiant Cells
- Structural Spongiotrophoblasts

Question 9

What are syncytiotrophoblasts?

Answer 9

Syncytiotrophoblasts control both maternal adaptive and innate immunity,

Physical separation

Express cell surface non-classical MHCI molecules (rather HLA C-E-G)
- These inhibit NK cells, suppress CTL activity and up-regulate the local CD4’ Treg cell differentiation.

They block innate immunity via the modification of neutrophil function and NET formation.

They produce hCG- signal to mother pregnancy has started

Question 10

What happens to the corpus luteum if there is no embryo?

Answer 10

LH (from pituitary) reduces, putting the Corpus Luteum (CL) at risk after ovulation (-ve feedback Progesterone - LH)

In absence of embryo, CL will die (10-14 days after ovulation due to -ive feedback

Question 11

What happens to the corpus luteum if there is a pregnancy?

Answer 11

Embryo implants

Syncitiotrophoblasts function and produce hCG

*hCG survival factor for CL.
*Prevents CL degeneration.
*80% identical LH.
*hCG Much longer half-life in blood
*hCG maintains progesterone formation
*Progesterone from CL switches off LH (-ve FB)
*Progesterone has no effect on hCG production (no -ve FB)

Question 12

What does progesterone do during pregnancy?

Answer 12

• Blocks further follicle development and ovulation (blocks FSH and LH)- so single embryo (or one timed wave of ovulation).
• Produces a barrier at cervix, mucus plug stops microorganism and sperm entry. Cervical plug.
• Induces uterine endometrium to make a nutrient-rich food source for embryo (secretory phase- needs estrogen too).
• Keeps uterine myometrium ‘quiescent’.
• Progesterone initially made by CL, later in pregnancy by placental syncytiotrophoblast (4-7 weeks) luteoplacental shift.
• Induces breast tissue growth ready for lactation.

Question 13

How does the placenta form?

Answer 13

At human E14 Cytotrophoblasts grow out into the endometrium increasing the contact surface of the primary chorionic villus

At human E16 Extra-embryonic mesoderm grows out into the primary villi increasing the contact surface further - the secondary chorionic villus

At human E20, vessels form in the secondary villi mesoderm- this forms the tertiary chorionic villus, and cytotrophoblast cells cover the syncytial cells– the cytotrophoblast shell

Question 14

VIDEO ON PLACENTA FORMATION

Answer 14

https://www.youtube.com/watch?v=bped-RVWsLk

Question 15

What are trophoblast giant cells and what do they do?

Answer 15

They are highlypolyploid (switched from a mitotic to endoreduplicativecell)

Like metastatic tumourcells, they breachbasement membranesand invade deeply into the maternal decidualized uterinestroma.

Highly angiogenic and vasodilatory properties, remodel arterial walls, enable them to redirectmaternal bloodflow towards theimplantationsite.

Question 16

What are the four types of trophoblastic giant cells, and what are their roles in placental development?

Answer 16

Spiral Artery-Associated Trophoblast Giant Cells:
- These cells are involved in remodeling the maternal spiral arteries, ensuring they are wide enough to supply the necessary blood volume to the growing fetus, enhancing maternal blood flow to the placenta.

Canal-Associated Trophoblast Giant Cells:
- Located in the vascular channels, these cells facilitate the restructuring of these canals to optimize nutrient and gas exchange between the mother and fetus.

Sinusoidal Trophoblast Giant Cells:
- These cells are positioned in the sinusoidal spaces of the placenta and help regulate the blood flow within these vascular spaces, crucial for effective fetal-maternal exchange.

Parietal Trophoblast Giant Cells:
- They are responsible for strengthening the structural integrity of the placenta by adhering to the parietal tissues of the uterus, playing a crucial role in anchoring the placenta.

Question 17

What are spongiotrophoblasts?

Answer 17

Cells forming between the villi and the cytotrophoblast cells

Between intervillous spaces which are flooded with maternal blood

Role Not Understood
- Structural
- Glycogen stores
- Intermediate stage between Cytotrophoblast and Giant cells

Question 18

Where does maternal vessel entry occur?

Answer 18

Maternal vessel entry and placental development doesn’t occur over the whole chorion

Villus formation is biased to the upper region – decidua basalis/ placentalis

Question 19

Shape and size of placenta

Answer 19

In humans and rodents a discoid placenta,

The placenta averages 22-24cm diameter and 2cm thick
Typically weighs 500grams

It connects to the foetus by anumbilical cordof approximately 55–60cm long

Contains twoumbilical arteriesand oneumbilical vein.

The shape alters between different mammalian species.

Question 20

What are the main substances transferred to the feotus?

Answer 20

From themotherto thefoetus
- Water,oxygen, nutrients and IgG antibodies.
(neonatal Fc receptor (FcRn) on syncytiotrophoblast).

From thefoetusto themother
- Metabolic wastes, including urea, uric acid, andcreatinine (via developing foetal kidney and the allantois)
- Carbon dioxide and heat.

Under normal conditions, maternal cellsdo notcross the placenta during gestation.

Placental barrier. Although permeable to some substances (selective permeability), the placental barrier largely prevents the passage of cells.

However foetal cells are highly invasive – and often enter the mothers tissues

Question 21

When does the amnion start to form?

Answer 21

Amnion precursors start to appear in man just after implantation

The epiblast forms an epithelial plate with a lumen in it

The lower surface is the epiblast and the upper are amnioblasts

As the amnion and the embryo grow, the amnion starts to rotate

Question 22

What happens to the amnion as the embryo starts to grow?

Answer 22

As the embryo folds – head and tail, and to the sides (forming a cavity in the embryo) it pulls the amnion around

So that the amnion surrounds almost all the embryo
– except for its junction with the yolk sac/ allantois and body stalk

Question 23

Amnion function

Answer 23

When first formed, the amniotic membrane is in contact with body of the embryo

Its begins to secrete amniotic fluid ~ 5 weeks in man and the amnion expands to ultimately adhere to the inner surface of thechorion

The amniotic fluid allows the free movements of the foetus during the later stages of pregnancy, and also protects it from trauma and maintains temperature

Question 24

When is the yolk sac developed?

Answer 24

This develops just after implantation (final position differs in varying mammalian species)

The primitive endoderm (hypoblast) begins to migrate out from the embryonic disc

This layer (now called parietal endoderm) in time covers the inner cytotrophoblasts .

• The spaces created are the extra embryonic coelom and primary yolk sac

(in man this forms about days 9-After this forms the chorionic growth becomes predominant

Question 25

What is the extra-coelomic cavity?

Answer 25

In man at ~ E12 extraembronic mesoderm grows out between the cytotrophoblasts and the parietal endoderm and then opens to form a wider extra-coelomic cavity

Question 26

What happens after the primary yolk sac and extra-coelomic cavity is formed?

Answer 26

The primary yolk sac pinches into two and forms the secondary yolk sac

Question 27

What differences are there in the yolk sac of humans and mice?

Answer 27

In the end the yolk sac in both has a stalk attaching to the abdomen of the foetus as it curves in at its head and side

In mice the rotation causes the amnion to sit around the embryo and down growth causes the yolk sac to surround them both

In man the yolk sac is pinched of and remains a bag and the embryo folds about its attachment point

Question 28

What is the role of the yolk sac?

Answer 28

1) Early nutrient transfer important in man from E15 to ~ 3mths

• The only point of nutrient transfer in reptiles and birds
• Main storage of nutrients during embryogenesis here

2) Vascular components – preliminary circulatory cells

• First site of haematopoiesis during mammalian development.
• Yolk sac hematopoietic stem cells (YS-HSC), these form and amplify here and then migrate into the embryo proper

The yolk sac is also the first site of blood vessel endothelial development. (blood islands) in the yolk sac

3) Primordial germ cells migrate from the primary ectoderm into the yolk sac (~E20 in man) near the exit of the allantois

• The primordial germ cellsmoveback into the embryo between the fourth and sixth week along the yolk sac/ allantois wall into the wall of the gut to colonize the gonadal ridge

Question 29

Where does the allantois come from?

Answer 29

This is an outgrowth (diverticulum) initially from the yolk sac and pushes into the stalk joining to the chorion
(part of the umbilicus), in man ~E16

In the embryo it extends from the hind gut

It fuses with the chorion and so in time forms the chorioallantoic membrane

Question 30

What does the allantois do?

Answer 30

In contact with the bladder and lets excreted fluids, urea (kidney)- be taken to placenta where transferred to maternal circulation

In birds / reptile – no placenta so this is a large structure

In mammals it is small as chorio-allantois allows transfer over placenta to mothers circulation

Question 31

What are the contents of the primitive umbilical cord?

Answer 31

1- Yolk sac and vitelline duct.

2- Connecting stalk with remnant of allantois

3- Umbilical and vitelline vessels.

4- Intestinal loop in its proximal part.

Question 32

Do the 4 membranes have blood supply?

Answer 32

yolk sac, allantois and chorionall have extensive vasculature

The amnion has no blood supply

Question 33

What are the differences in the membranes in the different vertebrate species?

Answer 33

• In amphibians – vegetal pole – cellular yolk rich (no yolk sac)
• Infish, only the yolk sac is present.

The amnion is a specialisation for terrestrial survival preventing the embryo from drying out (land animals)

Inreptilesandbirds, in addition to the yolk sac, the amnion, the chorion and the allantois are also present
- The yolk sac and allantois are far larger in these (no placenta)
- The allantois doesn’t fuse with the chorion

In placental mammals, the chorion and the allantois specialise to form theembryonic chorioallantoic placenta – filtered waste from the developing kidney is lost into the allantois and exchanged at the placenta….the endometrium forms the maternal placenta

Question 34

Overview of bird membranes

Answer 34

Theamnionprotects the embryo in a sac filled withamniotic fluid.(shock absorber)

Theyolk saccontains yolk — the sole source of food until hatching. Yolk is a mixture of proteins andlipoproteins.- it is very large initially reducing during development

Thechorionlines the inner surface of the shell (which is permeable to gases) and participates in the exchange of O2and CO2between the embryo and the outside air.

Theallantoisstores metabolic wastes (chieflyuric acid) of the embryo and, as it grows larger through development, also participates in gas exchange.

Question 35

Membranes in twins

Answer 35

Two foetuses share a single placenta, (monochorionic twins) in ~75% of identical twins

The placenta may occur anywhere in relation to the stalk position (the umbilical chord)– there is no set or predictable pattern

Depending on where they implant, one foetus may get a lower share of the placental exchange than it’s co-twin.

Hence although identical twins share the same genetic material, they may actually grow quite differently.

Only~ 1% of identical twins share both a single placenta and a single amniotic sac, and this poses a further risk
unequal placental sharing and umbilical knotting