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AN78.1-5 | Second week of development — Part 2

Extraembryonic Mesoderm and the Chorionic Cavity (AN78.4)

By Day 12, a new tissue appears that profoundly reorganises the conceptus: the extraembryonic mesoderm. Understanding its origin, its layers, and the cavity it creates is essential for visualising how the early embryo is suspended within its membranes.

Figure: Extraembryonic Mesoderm and the Chorionic Cavity (AN78.4)

Origin

The extraembryonic mesoderm is a layer of loosely arranged cells that forms outside the embryonic disc. Its exact origin is debated — Langman's states it derives from the yolk sac endoderm (hypoblast), while Moore's emphasises a contribution from epiblast cells that migrate through the primitive streak region (though the streak formally appears in Week 3). For exam purposes, know that it is NOT the same as the intraembryonic mesoderm that forms during gastrulation. It forms before gastrulation and lies outside the embryonic disc.

The Two Layers

The extraembryonic mesoderm fills the space between the trophoblast shell (outer boundary) and the yolk sac + amnion (inner structures). Soon, small cavities (lacunae) appear within this mesoderm and coalesce to form a large cavity — the extraembryonic coelom (also called the chorionic cavity). This splits the extraembryonic mesoderm into two layers:

1. Somatic (parietal) extraembryonic mesoderm — lines the inner surface of the cytotrophoblast and covers the outer surface of the amnion. This layer, together with the trophoblast, forms the chorion — the outermost fetal membrane. The chorion is the membrane that interfaces with the maternal endometrium and will develop into the fetal part of the placenta.

2. Splanchnic (visceral) extraembryonic mesoderm — covers the outer surface of the yolk sac. This layer, together with the yolk sac endoderm, forms the wall of the yolk sac.

The Connecting Stalk

When the chorionic cavity forms, it almost completely separates the embryo from the trophoblast shell — but not quite. A bridge of extraembryonic mesoderm connects the embryonic disc to the chorion at one point. This bridge is the connecting stalk (also called the body stalk). It is the precursor of the umbilical cord.

Inside the connecting stalk, you will later find:
- The allantois (an endodermal outgrowth from the yolk sac)
- The umbilical vessels (two arteries, one vein)

Visualising the Architecture at Day 14

By the end of the second week, the conceptus has a layered, nested architecture. From outside to inside:

1. Endometrium (maternal tissue)
2. Syncytiotrophoblast (outer trophoblast, with lacunae containing maternal blood)
3. Cytotrophoblast (inner trophoblast, stem cell layer)
4. Somatic extraembryonic mesoderm (lines the trophoblast from inside)
5. Chorionic cavity (fluid-filled space — the extraembryonic coelom)
6. Amnion + amniotic cavity (covering the dorsal surface of the epiblast)
7. Bilaminar disc (epiblast dorsally, hypoblast ventrally)
8. Yolk sac (lined by hypoblast, covered by splanchnic extraembryonic mesoderm)
9. Connecting stalk (bridging the disc to the chorion)

This nested "Russian doll" arrangement is the spatial framework you need for all subsequent embryology. Every structure you study in Week 3 and beyond fits into this scaffold.

The Prochordal Plate Revisited

Recall that the prochordal plate — where epiblast and hypoblast are fused — marks the cranial end of the embryo. At the opposite (caudal) end, the connecting stalk attaches. So by Day 14, the embryo has:
- A dorsoventral axis (epiblast = dorsal, hypoblast = ventral)
- A craniocaudal axis (prochordal plate = cranial, connecting stalk = caudal)
- A left-right axis (not yet determined — this requires the node, which appears in Week 3)

Two of three body axes are established before gastrulation even begins.

The Decidual Reaction, Pregnancy Tests, and Early Pregnancy Loss (AN78.5)

While the embryo is busy burrowing into the endometrium, the endometrium itself is undergoing dramatic changes in response. This maternal response is the decidual reaction, and it is essential for a successful pregnancy.

Figure: The Decidual Reaction, Pregnancy Tests, and Early Pregnancy Loss (AN78.5)

The Decidual Reaction

As the blastocyst implants, the endometrial stromal cells around the implantation site undergo a transformation:

• They swell and accumulate glycogen and lipid droplets (these nutrients will feed the embryo before the placental circulation is established)
• They become large, pale, polygonal cells called decidual cells
• The intercellular spaces fill with extravasated blood and edema fluid
• A dense network of new capillaries forms around the implantation site

This process is called decidualisation, and the transformed endometrium is called the decidua (from Latin: deciduus = falling off — because it will be shed at delivery, along with the placenta).

The decidua is divided into three regions based on their relationship to the embryo:

• Decidua basalis — the endometrium directly beneath the embryo (between embryo and myometrium). This will become the maternal component of the placenta.
• Decidua capsularis — the thin layer of endometrium that covers the embryo on the uterine cavity side (between embryo and uterine lumen). As the embryo grows, the capsularis stretches, thins, and eventually fuses with the opposite wall.
• Decidua parietalis (also called decidua vera) — all the remaining endometrium that is not in direct contact with the embryo. Lines the rest of the uterine cavity.

Human Chorionic Gonadotropin (hCG)

The syncytiotrophoblast begins producing hCG as early as Day 8–9, and the hormone enters the maternal bloodstream through the lacunar circulation. hCG has one primary job during early pregnancy: rescue the corpus luteum.

Without pregnancy, the corpus luteum degenerates around Day 24–26 of the menstrual cycle (about 10–12 days after ovulation). Progesterone drops, the endometrium sheds, and menstruation occurs. But hCG mimics LH (luteinising hormone — it binds the same receptor) and tells the corpus luteum to keep producing progesterone and oestrogen. This maintains the decidua and prevents menstruation.

The corpus luteum sustains the pregnancy until about Week 8–10, after which the placenta itself takes over hormone production (the luteoplacental shift).

Pregnancy Tests

Urine tests detect hCG using monoclonal antibodies immobilised on a test strip (immunochromatography). They become positive around Day 28 of the menstrual cycle (about 14 days after fertilisation) — roughly when the next period would have been expected. Sensitivity: most commercial kits detect hCG at 25 mIU/mL.

Blood tests (serum beta-hCG) are more sensitive and can detect hCG earlier — as low as 5 mIU/mL, detectable about 8–10 days after fertilisation. Serial beta-hCG measurements are used to:
- Confirm a viable intrauterine pregnancy (hCG should double every 48–72 hours in early pregnancy)
- Diagnose ectopic pregnancy (hCG rises but more slowly than expected, or plateaus)
- Monitor after miscarriage or ectopic treatment (hCG should fall to zero)
- Screen for gestational trophoblastic disease (molar pregnancy — abnormally high hCG)

Early Pregnancy Loss

Most pregnancy losses occur during the first two weeks — often before the woman knows she is pregnant. Causes include:

• Chromosomal abnormalities in the embryo (most common cause — ~50% of early losses)
• Failed implantation — blastocyst fails to adhere to the endometrium
• Inadequate decidual reaction — poor progesterone support
• Endometrial factors — polyps, adhesions (Asherman's syndrome), thin endometrium

These losses present as a late period or a slightly heavier-than-usual period. They are sometimes called chemical pregnancies — a positive pregnancy test followed by a period, with no ultrasound evidence of a pregnancy sac.

Contraceptive Relevance

Some contraceptive mechanisms target the second week:

• Intrauterine devices (IUDs) — create a hostile endometrial environment that impairs implantation (copper IUDs) or thickens cervical mucus and thins the endometrium (hormonal IUDs)
• Emergency contraception (levonorgestrel, ulipristal) — primarily delays ovulation, but may also impair endometrial receptivity if taken post-ovulation
• Mifepristone (RU-486) — a progesterone antagonist that blocks the decidual reaction, used in medical termination of early pregnancy

The "Week of Twos" — Putting It All Together

The second week of development is classically called the "Week of Twos" because nearly every structure that forms comes in pairs or has a dual nature. This mnemonic framework helps you remember the key events:

The Twos

Structure	The "Two"
Trophoblast	Two layers: cytotrophoblast + syncytiotrophoblast
Embryoblast	Two layers: epiblast + hypoblast (= bilaminar disc)
Cavities	Two new cavities: amniotic cavity + yolk sac (primary, then secondary)
Extraembryonic mesoderm	Two layers: somatic (parietal) + splanchnic (visceral)
Nutrition source	Two modes: histotrophic (gland secretions) → haemotrophic (maternal blood)

Integration: What Sets Up the Third Week

The architecture established by Day 14 directly enables gastrulation (Week 3):

• The epiblast will form the primitive streak — the structure through which cells migrate to create the three germ layers (ectoderm, mesoderm, endoderm)
• The prochordal plate tells the primitive streak where to stop — it defines the head end and prevents mesoderm from forming in the oropharyngeal region
• The yolk sac plays a role in early blood cell formation (haematopoiesis begins in the yolk sac wall in Week 3)
• The connecting stalk will carry the umbilical vessels once the allantois grows into it
• The chorionic villi (beginning as cytotrophoblast columns at Day 13–14) will mature into the functional placenta

Common Exam Errors

Students frequently confuse the following. Clarify now:

1. Cytotrophoblast vs. syncytiotrophoblast: The cytotrophoblast divides; the syncytiotrophoblast invades but does NOT divide. The syncytiotrophoblast grows only by fusion of cytotrophoblast cells.
2. Primary vs. secondary yolk sac: The primary yolk sac is lined by Heuser's membrane; it is pinched off and replaced by the smaller secondary (definitive) yolk sac. The remnants of the primary yolk sac are the exocoelomic cysts.
3. Extraembryonic vs. intraembryonic mesoderm: Extraembryonic mesoderm forms in Week 2, before gastrulation. Intraembryonic mesoderm forms in Week 3, during gastrulation (through the primitive streak). They are different in origin and location.
4. Chorion vs. amnion: The chorion = trophoblast + somatic extraembryonic mesoderm (outer membrane, contacts maternal tissue). The amnion = amnioblasts from the epiblast (inner membrane, faces the embryo). At birth, you see two membranes — the chorion (thicker, outer) and the amnion (thin, inner, contains the amniotic fluid).
5. Decidua basalis vs. capsularis: Basalis = under the embryo (becomes placenta). Capsularis = over the embryo (stretches and fuses with parietalis as the fetus grows).

Timeline Summary

Day	Key Event
6–7	Apposition and adhesion of blastocyst to endometrium
7–8	Trophoblast differentiates into cyto- and syncytiotrophoblast; bilaminar disc forms
8	Amniotic cavity appears; syncytiotrophoblast invades endometrial stroma
9	Blastocyst fully embedded; closing plug seals entry; Heuser's membrane + primary yolk sac form
10–11	Lacunae appear in syncytiotrophoblast; prochordal plate defined
12	Extraembryonic mesoderm appears; lacunar circulation begins (maternal blood in lacunae)
13	Extraembryonic coelom (chorionic cavity) forms; secondary yolk sac replaces primary
14	Primary chorionic villi begin; connecting stalk defined; two body axes established