Bilaminar Embryo

Question 1

What are the two stages of implantation?

Answer 1

Attachment and invasion

Question 2

What are the two stages of attachment?

Answer 2

Apposition - Pinopodes (protrusions of uterine epithelium) interdigitate with microvilli on surface of trophoblast

Adhesion - Integrin receptors on embryonic pole of blastocyst bind extracellular matrix created by trophoblast and uterine epithelium

Question 3

What are the two layers that the trophoblast differentiates into during invasion?

Answer 3

Cytotrophoblast - inner layer, mononuclear mitotically active which gives rise to outer layer
Syncytiotrophoblast - outer layer, multinucleated mass with no plasma membrane between cells. Penetrates through uterine epithelium first

Question 4

What two compounds does the syncytiotrophoblast secrete?

Answer 4

1. Matrix metalloproteases - degrade components of basement membrane and extracellular matrix of uterine epithelium
2. Human chorionic gonadotropin - responsible for maintaining corpus luteum in ovary, preventing it from becoming corpus albicans

Question 5

What are the two distinct cell layers that emerge once the blastocyst invades the uterine epithelium?

Answer 5

Embryoblast cells differentiate into epiblast (facing trophoblast) and hypoblast (facing blastocyst cavity)

Question 6

What are amnioblasts and when do they form?

Answer 6

Differentiated from epiblast cells to form the amniotic cavity, they are adjacent to the trophoblast and will form the amniotic membrane.

Question 7

When is the bilaminar embryo considered formed?

Answer 7

Around day 8-9, two adjacent layers of hypoblast and epiblast

Question 8

What forms the Heuser’s membrane?

Answer 8

Also called the exocoelomic membrane, hypoblast cells proliferate and migrate along inner surface of trophoblast / blastocyst cavity. The new layer of hypoblast cells around the cytotrophoblast is called the Heuser’s membrane.

Question 9

What is the primary (primitive) yolk sac?

Answer 9

Former blastocyst cavity which is now surrounded by Heuser’s membrane. It forms around the same time as the amniotic cavity.

Question 10

What forms the extraembryonic mesoderm?

Answer 10

Some of the hypoblast cells of Heuser’s membrane differentiate into mesenchymal cells and fill the space between Heuser’s membrane and the cytotrophoblast cells with mesenchymal cells

Question 11

What is epithelial to mesenchymal transformation?

Answer 11

EMT - epithelial cells get off basal lamina and begin expressing mesenchymal proteins like vimentin and demonstrate invasive motility and shape change. First occurs to form extraembryonic mesoderm

Question 12

What lies between the amnion and cytotrophoblast around days 11-12?

Answer 12

Extraembryonic mesoderm expands around this area (originally proliferates between Heuser’s membrane and cytotrophoblast)

Question 13

How is the extraembryonic coelom formed?

Answer 13

Small lacunae appear in the extraembryonic mesoderm and coalesce. Within 24 hours, this chorionic cavity is formed.

Question 14

What are the two layers of the extraembryonic mesoderm after the chorionic cavity is formed?

Answer 14

1. Splanchnopleuric mesoderm - lines the primary yolk sac

2. Somatopleuric mesoderm - lines the cytotrophoblast and continues around amniotic cavity

Question 15

What forms the extraembryonic endoderm?

Answer 15

While the chorionic cavity is forming, a second wave of hypoblast cells proliferates and displaces the Heuser’s membrane lining the primary yolk sac. These hypoblast cells which line the splanchnopleuric mesoderm become the extraembryonic endoderm.

Question 16

What forms the secondary / definitive yolk sac?

Answer 16

Cavity lined by migrating extraembryonic endoderm, it is much smaller than primary yolk sac.

Question 17

How are the exocoelomic cysts formed?

Answer 17

Chorionic cavity expands and pinches off the primary yolk sac during formation of secondary (definitive) yolk sac. These are pushed to the abembyronic pole of the chorionic cavity and gradually disappear into the extraembryonic mesoderm.

Question 18

What is the function of the connecting stalk?

Answer 18

It is a mass of extraembryonic mesoderm which connects the embryo to the chorionic plate, since the chorionic cavity is getting much larger.

Question 19

What is the chorionic plate?

Answer 19

Also called chorion, it is the wall of the chorionic cavity. It is somatopleuric mesoderm + cytotrophoblast + syncytiotrophoblast

Question 20

What is the role of the secondary (definitive) yolk sac in humans?

Answer 20

Transfer nutrients in weeks 2 and 3 before the uteroplacental circulation is established. Hemopoesis first occurs in the vascularized extraembryonic splanchnopleuric mesoderm until week 6 it starts in liver. Will also give rise to primordial germ cells in endodermal layer.

Question 21

When does the primitive placenta start to form?

Answer 21

Around the same time as the formation of the primary yolk sac (Heuser’s membrane bounds it)

Question 22

What are trophoblastic lacunae?

Answer 22

Structures of the syncytiotrophoblast which anastomose to create a lacunar network. They surround capillaries and get filled with maternal blood.

Question 23

What forms the primary stem villi / primary chorionic stem villi?

Answer 23

Proliferating cytotrophoblast cells. These chorionic stem villi undergo many transformations to come in contact with the lacunar network inside syncytiotrophoblast cells

Question 24

What are the three stages of transformation of the chorionic stem villi?

Answer 24

1. primary - columns of cytotrophoblast surrounded by syncytiotrophobolast
2. secondary - extraembyronic somatopleuric mesoderm invades to form core
3. tertiary - mesenchymal cells in the extraembryonic somatopleuric mesoderm differentiate into capillaries and blood cells

Question 25

How does blood get into the embryo?

Answer 25

Tertiary chorionic stem villi capillaries form arteriocapillary networks. They connect with embryonic blood vessels through the connecting stalk and attach to embryonic heart. Blood is flowing by end of week 3. (primitive placenta)

Question 26

What is early spontaneous abortion? (ESA)

Answer 26

Pregnancy loss during first 3 weeks, might be high as 50% rate. random event that often goes undetected

Question 27

What is recurrent spontaneous abortion? RSA

Answer 27

Three or more consecutive pregnancy losses prior to the 20th week of gestation. Causes may include genetic / anatomical anamolies, endocrine or immunological factors, infections, or teratogens. Happens more with increasing maternal age.

Question 28

What is the primary cause of most RSA?

Answer 28

90% is caused by genetic anomalies, especially poly or monoploidy of X chromosome. 54% have normal karyotype, just some wrong genes

Question 29

What is ectopic pregnancy and its main causes?

Answer 29

Pregnancy resulting from embryo implantation outside normal uterine sites. Blastocyst implants in abdominal cavity or uterine tube. Most are tubal pregnancies.

Causes: infections, inflammation, scar tissue from previous surgery in the area, or abnormal uterine tube development

Question 30

What is the most common cause of ectopic pregnancy?

Answer 30

Pelvic inflammatory disease -> generally as a result of certain STDs such as gonorrhea or chlamydia

Question 31

What are the diagnostic signs and treatment of ectopic pregnancy?

Answer 31

Severe abdominal pain, often associated with severe internal bleeding. Can be diagnosed by ultrasound and treated by surgical removal of ectopic embryo

Question 32

What is a complete hydatidiform mole (CHM)?

Answer 32

Human conceptus that develops into a disorganized mass of placental derivatives, generally associated with two sets of paternal chromosomes. They are mostly cytotrophoblast with some syncytiotrophoblast

Question 33

How can two paternal pronuclei occur?

Answer 33

1. Two sperm invade egg and maternal pronuclei is expelled

2. Materal pronuclei is expelled and paternal pronuclei divides

Question 34

How is genetic imprinting involved in CHM formation?

Answer 34

When two male pronuclei are in the blastocyst, maternally expressed imprinted genes are not expressed. For trophoblast, maternally imprinted genes are not required, so this will proliferate. Maternally and paternally expressed is required for embryonic development.

Question 35

What is recurrent biparental mole?

Answer 35

Familial cases of CHM can happen with both maternal and paternal chromosomes as a result of autosomal mutations which suppression maternally imprinted genes

Question 36

How is CHM diagnosed and treated?

Answer 36

Diagnosis:
Vaginal bleeding towards end of first trimester. Ultrasound shows no fetus. hCG levels will become very high early on
Treatment:
Surgical removal and chemotherapy with methotrexate if cannot be fully removed (cancerous)

Question 37

What is choriocarcinoma?

Answer 37

Aggressive cancer from malignant transformation of a trophoblast. ~50% are preceded by CHM, rest are normal preg, ectopic, or abortion.

Question 38

How does choriocarcinoma metastasize and what are the signs?

Answer 38

Generally early spread to the lungs. Other regions may be included.
Diagnosis:
Excessive hCG.
Vaginal bleeding
Chest pain and chest X-ray infiltrates (lung metastasis)
Coughing up blood, SOB

Question 39

What is the treatment for choriocarcinoma?

Answer 39

1. Surgical removal
2. Methotrexate chemotherapy.
   Remission can be monitored by hCG levels