Chapter 4

Overview of the Second Week of Development:

 Development rates among embryos of the same fertilization age may vary significantly.
 The second week focuses on the formation of essential structures within the blastocyst,
such as the trophoblast, embryoblast, and related cavities.

Day 8 - Key Events:

1. Blastocyst Implantation:
o The blastocyst is partially embedded in the endometrial stroma, initiating early
stages of implantation.
2. Trophoblast Differentiation:
o Trophoblast develops into two distinct layers:
 Cytotrophoblast:
 Composed of mononucleated cells.
 Mitotically active; cells divide and migrate outward.
 Syncytiotrophoblast:
 A multinucleated layer with no distinct cell boundaries.
 Receives cells from the cytotrophoblast, where they fuse.
3. Embryoblast Differentiation:
o The embryoblast (inner cell mass) forms a bilaminar germ disc, consisting of:
 Hypoblast Layer:
 Small cuboidal cells adjacent to the blastocyst cavity.
 Epiblast Layer:
 Tall columnar cells adjacent to the newly forming amniotic cavity.
4. Formation of the Amniotic Cavity:
o A small cavity forms within the epiblast and expands into the amniotic cavity.
o Amnioblasts: Epiblast cells lining the cavity, which help form the boundary.
5. Changes in the Endometrium:
o Endometrial stroma near the implantation site:
 Becomes edematous (swollen due to fluid accumulation).
 Shows increased vascularization and tortuous glands.
 Glands secrete glycogen and mucus, essential for nourishing the embryo.

Questions for Review:

1. Explain the structural differences between the cytotrophoblast and

syncytiotrophoblast.
 2. What are the two layers of the embryoblast, and what type of cells constitute each
layer?
3. Describe the formation and significance of the amniotic cavity.
4. What changes occur in the endometrial stroma during implantation, and why are
they important?
5. Why is mitotic activity observed only in the cytotrophoblast and not in the
syncytiotrophoblast?

Notes: Day 9 of Development

1. Lacunar Stage of Trophoblast Development:

 The blastocyst becomes more deeply embedded in the endometrium.

 Vacuoles form within the syncytiotrophoblast.
o These vacuoles fuse to form larger spaces called lacunae.
o This phase is referred to as the lacunar stage (see Fig. 4.3).

2. Closure of Penetration Defect:

 The penetration defect in the surface epithelium (from blastocyst implantation) is sealed
by a fibrin coagulum.

3. Formation of the Exocoelomic Membrane:

 At the abembryonic pole (opposite the site of the embryoblast):

o Flattened cells, likely originating from the hypoblast, form the exocoelomic
(Heuser) membrane.
o This membrane lines the inner surface of the cytotrophoblast.

4. Development of the Primitive Yolk Sac:

 The exocoelomic membrane combines with the hypoblast to create the lining of the
exocoelomic cavity.
o This cavity is also known as the primitive yolk sac.
5. Bilaminar Disc Structure:

 The bilaminar germ disc remains prominent:

o Epiblast layer: High columnar cells adjacent to the amniotic cavity.
o Hypoblast layer: Cuboidal cells adjacent to the primitive yolk sac.

Questions for Review:

1. What characterizes the lacunar stage of trophoblast development?

2. How is the penetration defect in the endometrium closed?
3. Describe the origin and function of the exocoelomic (Heuser) membrane.
4. What is the significance of the primitive yolk sac, and how is it formed?
5. Differentiate between the epiblast and hypoblast in the bilaminar germ disc.

Notes: Days 11 and 12 of Development

1. Complete Embedding of the Blastocyst:

 By Days 11 and 12, the blastocyst is fully embedded in the endometrial stroma.
 The original defect in the uterine wall is nearly covered by the surface epithelium.
 The blastocyst causes a slight protrusion into the uterine lumen.

2. Development of Trophoblast and Lacunar System:

 Lacunar spaces in the syncytiotrophoblast form an intercommunicating network,

especially prominent at the embryonic pole.
 The cytotrophoblast dominates the abembryonic pole.

3. Formation of Uteroplacental Circulation:

 Syncytiotrophoblast cells:
o Penetrate deeper into the endometrial stroma.
o Erode the endothelial lining of maternal capillaries (dilated capillaries are called
sinusoids).
o Syncytial lacunae connect with maternal sinusoids, allowing maternal blood to
flow through the lacunar system.
o Establishes the uteroplacental circulation.
4. Formation of the Extraembryonic Mesoderm and Chorionic Cavity:

 A new layer, the extraembryonic mesoderm, appears between the:

o Inner surface of the cytotrophoblast.
o Outer surface of the exocoelomic cavity.
 Origin: Derived from yolk sac cells.
 Development:
o Large cavities form in the extraembryonic mesoderm.
o These cavities merge to create the extraembryonic cavity (chorionic cavity).
o The chorionic cavity surrounds the primitive yolk sac and amniotic cavity,
except where the germ disc remains attached to the trophoblast by the connecting
stalk.

5. Specialized Regions of the Extraembryonic Mesoderm:

 Extraembryonic somatic mesoderm:

o Lines the cytotrophoblast and amnion.
 Extraembryonic splanchnic mesoderm:
o Covers the yolk sac.

6. Growth of Bilaminar Germ Disc:

 The bilaminar disc grows more slowly compared to the trophoblast, remaining small
(0.1–0.2 mm).

7. Decidual Reaction:

 Changes in the endometrial stroma include:

o Cells become polyhedral and rich in glycogen and lipids.
o Intercellular spaces fill with extravasate.
o The stroma becomes edematous.
 These changes are initially localized to the implantation site but later spread throughout
the endometrium.

Questions for Review:

 1. What are the main structural changes observed in the blastocyst by Days 11 and 12?
2. Describe the formation and significance of the uteroplacental circulation.
3. What is the origin of the extraembryonic mesoderm, and what structures does it
form?
4. Differentiate between the extraembryonic somatic and splanchnic mesoderm.
5. What is the decidual reaction, and why is it important for implantation?

Notes: Day 13 of Development

1. Healing of the Surface Defect:

 By Day 13, the surface defect in the endometrium is usually healed.

 Occasional Bleeding:
o Increased blood flow into the lacunar spaces may cause bleeding at the
implantation site.
o This bleeding, occurring near the 28th day of the menstrual cycle, can be
mistaken for menstrual bleeding, leading to errors in calculating the expected
delivery date.

2. Formation of Primary Villi:

 The trophoblast develops villous structures:

o Cytotrophoblast cells proliferate locally.
o These cells penetrate the syncytiotrophoblast, forming cellular columns
surrounded by syncytial covering.
o These structures are called primary villi.

3. Development of the Secondary Yolk Sac:

 Hypoblast cells produce new cells that migrate along the exocoelomic membrane.
 These cells form the secondary yolk sac (definitive yolk sac), which:
o Is smaller than the original primitive yolk sac.
o Develops as large portions of the exocoelomic cavity are pinched off, forming
exocoelomic cysts.
o These cysts are often found in the chorionic cavity.

4. Expansion of the Chorionic Cavity:

  The extraembryonic coelom expands, forming the chorionic cavity.
 The extraembryonic mesoderm lining the cytotrophoblast becomes the chorionic plate.

5. Formation of the Umbilical Cord:

 The connecting stalk is the only structure traversing the chorionic cavity.
 As blood vessels develop in the connecting stalk, it becomes the umbilical cord.

Questions for Review:

1. Why might bleeding occur at the implantation site, and how can it affect pregnancy
dating?
2. What are primary villi, and how are they formed?
3. Explain the process of secondary yolk sac formation. How does it differ from the
primitive yolk sac?
4. What is the chorionic plate, and how is it formed?
5. Describe the transformation of the connecting stalk into the umbilical cord.

Notes: Abnormal Implantation

1. Role of Syncytiotrophoblast and Hormone Production:

 The syncytiotrophoblast is responsible for producing human chorionic gonadotropin

(hCG), a hormone detectable by pregnancy tests.
 hCG Detection:
o By the end of the second week of pregnancy, hCG levels are high enough to be
detected by radioimmunoassays, forming the basis for pregnancy tests.

2. Immune System Changes During Pregnancy:

 Immune Tolerance:
o The embryo’s genome is partly foreign (50% from the father), which can lead to
immune rejection, similar to organ transplants.
o To tolerate the pregnancy, the immune system shifts from cell-mediated
immunity to humoral immunity, helping protect the embryo.
  Increased Infection Risks:
o This immune shift increases susceptibility to infections like influenza, which can
be more dangerous for pregnant women.
 Autoimmune Disease Manifestations:
o Conditions like multiple sclerosis and rheumatoid arthritis improve during
pregnancy (cell-mediated).
o Systemic lupus erythematosus (antibody-mediated) worsens during pregnancy.

3. Abnormal Implantation Sites:

 Placenta Previa:
o In rare cases, implantation occurs near the internal os (opening) of the cervix,
leading to placenta previa, which can cause severe bleeding during pregnancy
and delivery.
 Ectopic Pregnancy:
o Ectopic pregnancies occur when implantation happens outside the uterus, such
as in the uterine tube, ovary, or abdominal cavity.
o 95% of ectopic pregnancies occur in the uterine tube, especially in the ampulla
region.
o Ectopic pregnancies account for 2% of all pregnancies and are responsible for 9%
of pregnancy-related maternal deaths.

4. Types of Ectopic Pregnancies:

 Abdominal Pregnancy:
o The most common site for implantation in the abdominal cavity is the
rectouterine pouch (pouch of Douglas).
o These pregnancies can result in severe complications and hemorrhaging.
 Ovarian Pregnancy:
o In rare cases, the blastocyst implants in the ovary, leading to a primary ovarian
pregnancy.

5. Abnormal Blastocysts and Their Fate:

 Abnormal Blastocysts:
o In a study of 26 blastocysts, 9 were found to be abnormal, showing conditions
like:
 Syncytium-only structures.
 Trophoblastic hypoplasia.
 Absent embryos or abnormal orientation of the germ disc.
  Hydatidiform Mole:
o In cases where the trophoblast develops but little or no embryonic tissue is
present, the condition is known as a hydatidiform mole.
o Moles can produce high levels of hCG and may lead to benign or malignant
tumors (e.g., choriocarcinoma).
o Hydatidiform moles arise from unfertilized eggs that lack a nucleus, followed by
duplication of the male chromosomes, leading to a diploid genome entirely
from the father.

6. Genetic Aspects and Genomic Imprinting:

 Genetic Differences Between Maternal and Paternal Genes:

o Genomic imprinting refers to the phenomenon where the expression of certain
genes depends on whether they are inherited from the mother or the father.
o For example:
 A microdeletion on chromosome 15 inherited from the father causes
Prader-Willi syndrome.
 The same deletion inherited from the mother causes Angelman
syndrome.

7. Preimplantation and Postimplantation Reproductive Failure:

 Reproductive Failure Rates:

o 15% of oocytes are not fertilized, and 10-15% of fertilized oocytes fail to
implant.
o Of those that implant, 58% survive into the second week, but 16% are
abnormal.
o In total, only 42% of eggs exposed to sperm survive to the point of a missed
period.

Questions for Review:

1. What role does the syncytiotrophoblast play in pregnancy, and how is hCG used in
pregnancy tests?
2. How does the immune system change during pregnancy to tolerate the embryo?
3. What is placenta previa, and why can it be dangerous?
4. What are the different types of ectopic pregnancies, and where do they commonly
occur?
5. Explain the condition of a hydatidiform mole and its genetic origins.
6. What is genomic imprinting, and how does it affect certain genetic disorders?
7. What are the main causes of reproductive failure before and after implantation?