ABNORMAL EMBRYOS AND SPONTANEOUS ABORTIONS

of Down syndrome or other congenital anomalies in the child when the father is older than 50 years of age?

2. Are there oral contraceptives for men? If not, what is the reason?

3. Is a polar body ever fertilized? If so, does the fertil- ized polar body give rise to a viable embryo?

4. What is the most common cause of spontaneous abortion during the first week of development?

5. Could a woman have dissimilar twins as a result of one oocyte being fertilized by a sperm from one man and another one being fertilized by a sperm from another man?

6. When referring to a zygote, do the terms cleavage and mitosis mean the same thing?

7. How is the cleaving zygote nourished during the first week?

8. Is it possible to determine the sex of a cleaving zygote developing in vitro? If so, what medical reasons would there be for doing so?

The answers to these questions are at the back of this book.

C H A P T E R 3    FIRST WEEk OF HuMAN DEvELOPMENT 27.e1  

Answers to Chapter 3 Clinically Oriented Questions

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29

C H A P T E R

Second Week of

Human Development

4

Formation of Amniotic Cavity, Embryonic Disc, and Umbilical Vesicle 30

Development of Chorionic Sac 32

Implantation Sites of Blastocysts 33 Clinically Oriented Questions 34

mplantation of the blastocyst is completed during the second week of development.

As this process takes place, changes occur, producing a bilaminar embryonic disc composed of two layers, the epiblast and hypoblast (Fig. 4-1A). The embryonic disc gives rise to germ layers that form all the tissues and organs of the embryo. Extraembryonic structures forming during the second week include the amniotic cavity, amnion, umbilical vesicle (yolk sac), connecting stalk, and chorionic sac.

Implantation of the blastocyst is completed during the second week and normally occurs in the endometrium, usually superiorly in the body of the uterus and slightly more often on the posterior than on the anterior wall. The actively erosive syncytiotrophoblast invades the endometrial connective tissue that supports the uterine capillaries and glands. As this occurs, the blastocyst slowly embeds itself in the endometrium. Syncytiotrophoblastic cells from this region displace endometrial cells in the central part of the implantation site. The endometrial cells undergo apoptosis (programmed cell death), which facilitates implantation. Proteolytic enzymes produced by the syncytiotrophoblast are involved in this process. The uterine con- nective tissue cells around the implantation site become loaded with glycogen and lipids.

Some of these cells—decidual cells—degenerate adjacent to the penetrating syncytiotropho- blast. The syncytiotrophoblast engulfs these degenerating cells, providing a rich source of embryonic nutrition. As the blastocyst implants, more trophoblast contacts the endometrium and continues to differentiate into two layers (see Fig. 4-1A):

•

^The cytotrophoblast, a layer of mononucleated cells that is mitotically active. It forms new trophoblastic cells that migrate into the increasing mass of syncytiotrophoblast, where they fuse and lose their cell membranes.

•

The syncytiotrophoblast, a rapidly expanding, multinucleated mass in which no cell boundaries are discernible.

I

30 BEFORE WE ARE BORN    ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS

flattened, almost circular, bilaminar plate of cells—the embryonic disc—consisting of two layers (see Fig. 4-1B and Fig. 4-2B):

•

^The epiblast, the thicker layer, consisting of high, columnar cells related to the amniotic cavity

•

^The hypoblast, the thinner layer, consisting of small, cuboidal cells adjacent to the exocoelomic cavity Concurrently, a small cavity appears in the embryo- blast, which is the primordium of the amniotic cavity (Fig. 4-1A). Soon, amniogenic (amnion-forming) cells—

amnioblasts—separate from the epiblast and organize to form a thin membrane, the amnion, which encloses the amniotic cavity.

The syncytiotrophoblast produces a hormone, human chorionic gonadotropin (hCG), that enters the maternal blood in the lacunae in the syncytiotrophoblast (Fig.

4-1B). hCG maintains the development of spiral arteries in the myometrium and formation of the syncytiotropho- blast. It also forms the basis for pregnancy tests. Highly sensitive assays are available for detecting hCG at the end of the second week even though the woman is probably unaware that she is pregnant.

FORMATION OF AMNIOTIC CAVITY, EMBRYONIC DISC, AND UMBILICAL VESICLE

As implantation of the blastocyst progresses, changes occurring in the embryoblast result in the formation of a Figure 4–1  Implantation of blastocyst. The actual size of the  conceptus is approximately 0.1 mm. A, Illustration of a section of  a partially implanted blastocyst (approximately 8 days after fertil- ization).  Note  the  slit-like  amniotic  cavity. B,  Illustration  of  a  section through a blastocyst at approximately 9 days. 

Uterine gland Endometrial capillary

Syncytio- trophoblast

Amnion Endometrial epithelium Epiblast

Amniotic cavity

Exocoelomic

membrane Hypoblast

Cytotrophoblast Amnion

Maternal blood in lacunae Uterine gland

Bilaminar embryonic disc Endometrial epithelium Extraembryonic

mesoderm Primary

umbilical vesicle

Cytotrophoblast Exocoelomic

cavity

A

B

Figure 4–2  Illustration  of  sections  of  two  implanted  blasto- cysts at 10 days (A) and 12 days (B). 

A

B

Syncytiotrophoblast Amnion

Lacunar network Endometrial capillary

Epiblast Cytotro- phoblast

Extraembryonic mesoderm Primary

umbilical vesicle

Closing

plug Hypoblast

Eroded

gland Maternal

blood Lacunar network

Embryonic disc

Cytotrophoblast Amniotic cavity

Uterine gland

Extra- embryonic coelomic space Extra-

embryonic endodermal lining of the umbilical vesicle (yolk sac)

2

C H A P T E R 4    SECOND WEEk OF HuMAN DEvELOPMENT 31

Fig. 4-2B). These spaces rapidly fuse to form a large, isolated cavity, the extraembryonic coelom (Fig. 4-3A).

This fluid-filled cavity surrounds the amnion and umbili- cal vesicle, except where they are attached to the chorion by the connecting stalk. As the extraembryonic coelom forms, the primary umbilical vesicle decreases in size and a smaller, secondary umbilical vesicle forms (Fig. 4-3B).

During formation of the secondary umbilical vesical, a large part of the primary umbilical vesicle is pinched off.

The umbilical vesicle contains no yolk; however, it may have a role in the selective transfer of nutritive materials to the embryonic disc.

The epiblast forms the floor of the amniotic cavity and is continuous peripherally with the amnion. The hypo- blast forms the roof of the exocoelomic cavity and is continuous with the cells that migrated from the hypo- blast to form the exocoelomic membrane. This mem- brane surrounds the blastocystic cavity and lines the internal surface of the cytotrophoblast.

The exocoelomic membrane and cavity soon become modified to form the primary umbilical vesicle. The embryonic disc then lies between the amniotic cavity and primary umbilical vesicle (see Fig. 4-1B). The outer layer of cells from the umbilical vesicle endoderm forms a layer of loosely arranged connective tissue, the extraembryonic mesoderm (see Fig. 4-1B).

As the amnion, embryonic disc, and primary umbilical vesicle form, lacunae (small spaces) appear in the syncy- tiotrophoblast (see Figs. 4-1B and Fig. 4-2). The lacunae are soon filled with a mixture of maternal blood from ruptured endometrial capillaries and cellular debris from eroded uterine glands. The fluid in the lacunae—

embryotroph—passes to the embryonic disc by diffusion.

The communication of the eroded uterine vessels with the lacunae represents the beginning of the primordial utero- placental circulation. When maternal blood flows into the lacunae, oxygen and nutritive substances become available to the extraembryonic tissues over the large surface of the syncytiotrophoblast. Oxygenated blood passes into the lacunae from the spiral endometrial arter- ies in the endometrium (see Chapter 2, Fig. 2-2C); deoxy- genated blood is removed from the lacunae through endometrial veins.

The 10-day conceptus (embryo and extraembryonic membrane) is completely embedded in the endometrium (see Fig. 4-2A). For approximately 2 more days, there is a defect in the endometrial epithelium that is filled by a closing plug, a fibrinous coagulum of blood. By day 12, an almost completely regenerated uterine epithelium covers the closing plug (see Fig. 4-2B). As the conceptus implants, the endometrial connective tissue cells undergo a transformation—the decidual reaction—resulting from cyclic adenosine monophosphate and progesterone sig- naling. The cells swell because of the accumulation of glycogen and lipid in their cytoplasm, and they are then called secretory decidual cells. The primary function of the decidual reaction is to provide an immunologically privileged site for the conceptus.

In the 12-day embryo, adjacent syncytiotrophoblastic lacunae have fused to form lacunar networks (see Fig.

4-2B), the primordia of the intervillous space of the pla- centa (see Chapter 8). The endometrial capillaries around the implanted embryo become congested and dilated to form sinusoids, which are thin-walled terminal vessels that are larger than ordinary capillaries. The syncytiotro- phoblast then erodes the sinusoids and maternal blood flows into the lacunar networks. The degenerated endo- metrial stromal cells and glands, together with the mater- nal blood, provide a rich source of material for embryonic nutrition. Growth of the bilaminar embryonic disc is slow compared with the growth of the trophoblast.

As changes occur in the trophoblast and endometrium, the extraembryonic mesoderm increases and isolated extraembryonic coelomic spaces appear within it (see

Figure 4–3  Sections  of  implanted  embryos. A,  At  13  days. 

Note  the  decrease  in  the  relative  size  of  the  primary  umbilical  vesicle  and  the  appearance  of  primary  chorionic  villi. B,  At  14  days. Note the newly formed secondary umbilical vesicle. 

A

Maternal sinusoid Extraembryonic

somatic mesoderm Lacunar

network Primary chorionic villus

Chorionic sac

Endometrium

Extraembryonic

splanchnic mesoderm Extraembryonic coelom

Primary umbilical vesicle

B

Maternal blood Primary chorionic villus

Connecting stalk

Prechordal plate

Endometrial epithelium

Secondary umbilical vesicle

Extraembryonic somatic mesoderm Remnant

of primary umbilical

vesicle

32 BEFORE WE ARE BORN    ESSENTIALS OF EMBRYOLOGY AND BIRTH DEFECTS

•

The extraembryonic splanchnic mesoderm, which sur- rounds the umbilical vesicle

The growth of these cytotrophoblastic extensions is believed to be induced by the underlying extraembryonic somatic mesoderm. The extraembryonic somatic meso- derm and the two layers of trophoblast form the chorion.

The chorion forms the wall of the chorionic sac (see Fig.

4-3A). The embryo, amniotic sac, and umbilical vesicle are suspended in the chorionic cavity by the connecting stalk (see Fig. 4-3B and Fig. 4-4B). Transvaginal ultraso- nography (endovaginal sonography) is used to measure the diameter of the chorionic sac. This measurement is valuable for evaluating early embryonic development and pregnancy outcome.