the second w of human development - elsevier · conceptus is approximately 0.1 mm. a, illustration...

30

4THE SECOND WEEK OF HUMAN

DEVELOPMENT

Formation of the Amniotic Cavity and Embryonic Disc 31

Development of the Chorionic Sac 33

Implantation Sites of the Blastocyst 33

Clinically Oriented Questions 35

Ch04-X3705.indd 30Ch04-X3705.indd 30 6/26/07 11:29:39 AM6/26/07 11:29:39 AM

Implantation of the blastocyst is completed during the second week of embryonic development. As this cru-

cial process occurs, changes occur in the embryoblast, producing a bilaminar embryonic disc composed of two layers, the epiblast and the hypoblast (Fig. 4-1). The embryonic disc gives rise to the germ layers that form all the tissues and orans of the embryo. Extraembryonic structures forming during the second week include the amniotic cavity, amnion, umbilical vesicle (yolk sac), con-necting stalk, and chorionic sac.

Implantation of the blastocyst begins at the end of the first week. 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 faci litates implantation. Proteolytic enzymes produced by the syncytiotrophoblast are involved in this process. The uterine connective tissue cells around the implantation site become loaded with glycogen and lipids and assume a polyhedral appearance. Some of these cells—decidual cells—degenerate adjacent to the penetrating syncytiotrophoblast. 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 and B):• The cytotrophoblast, a layer of mononucleated cells

that is mitotically active and forms new tro phoblastic cells that migrate into the increasing mass of syncytiotrophoblast, where they fuse and lose their cell membranes• The syncytiotrophoblast, a rapidly expanding, multi-nucleated mass in which no cell boundaries are discernible

The syncytiotrophoblast produces a hormone, human chorionic gonadotropin (hCG), which enters the maternal blood in the lacunae in the syncytiotrophoblast (see Fig. 4-1C); hCG maintains the endocrine activity of the corpus luteum in the ovary during pregnancy and forms the basis for pregnancy tests. Highly sensitive radioimmunoassays are available for detecting hCG. Enough hCG is produced by the syncytiotrophoblast at the end of the second week to yield a positive pregnancy test, even though the woman is probably unaware that she is pregnant.

■ FORMATION OF THE AMNIOTIC CAVITY AND EMBRYONIC DISC

As implantation of the blastocyst progresses, changes occur-ring in the embryoblast result in the formation of a fl attened, almost circular, bilaminar plate of cells—the embryonic disc—consisting of two layers (Figs. 4-1A and 4-2B):• The epiblast, the thicker layer, consists of high, columnar

cells related to the amniotic cavity.• The hypoblast, the thinner layer, consists of small, cuboidal cells adjacent to the exocoelomic cavity.

Concurrently, a small cavity appears in the embryoblast, which is the primordium of the amniotic cavity (see Fig. 4-1A). Soon, amniogenic (amnion-forming) cells called

amnioblasts separate from the epiblast and organize to form a thin membrane, the amnion, which encloses the amniotic cavity (see Fig. 4-1A).

The epiblast forms the fl oor of the amniotic cavity and is continuous peripherally with the amnion. The hypoblast

Uterine gland Endometrial capillary

Syncytio-trophoblast

Amnion

Endometrialepithelium

Epiblast

Amniotic cavity

Exocoelomicmembrane Hypoblast

Syncytiotrophoblast

Amnion

Exocoelomic cavity

Cytotrophoblast

Amnion

Maternalblood inlacunae

Uterinegland

Bilaminarembryonicdisc

Endometrial epitheliumExtraembryonicmesoderm

Primaryumbilicalvesicle(yolk sac)

Exocoelomic membrane

Bilaminar embryonicdisc

CytotrophoblastExocoelomiccavity

A

B

C

FIGURE 4-1. Implantation of a 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 fertilization). Note the slitlike amniotic cavity. B, Illustration of a slightly older blastocyst (endometrium not shown). C, Illustration of a section through a blastocyst at approximately 9 days. Note the lacunae appearing in the syncytiotrophoblast. The term yolk sac is a misnomer because it contains no yolk.

The Second Week of Human Development ■ 31


32 ■ Before We Are Born

forms the roof of the exocoelomic cavity and is continuous with the cells that migrated from the hypoblast to form the exocoelomic membrane. This membrane 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 the primary umbilical vesicle. The outer layer of cells from the umbilical vesicle endoderm forms a layer of loosely arranged connective tissue, the extraembryonic mesoderm, which surrounds the amnion and the umbilical vesicle, formerly called the yolk sac (see Fig. 4-1C).

As the amnion, embryonic disc, and primary umbilical vesicle form, isolated cavities called lacunae appear in the syncytiotrophoblast (see Figs. 4-1C and 4-2). The lacunae soon become filled with a mixture of maternal blood from ruptured endometrial capillaries and cellular debris from eroded uterine glands. The fl uid in the lacunae, sometimes called embryotroph, passes to the embryonic disc by diffusion. The communication of the eroded uterine vessels with the lacunae represents the beginning of uteroplacental circulation. When maternal blood fl ows 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 arteries in the endometrium; deoxygenated blood is removed from the lacunae through endometrial veins.

The 10-day human embryo is completely embedded in the endometrium (see Fig. 4-2A). For approximately 2 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 known as the decidual reaction. The cells swell because of the accumulation of glycogen and lipid in their cytoplasm, and they are then known as decidual cells. The primary function of the decidual reaction is to provide an immunologically privileged site for the conceptus.

In a 12-day embryo, adjacent syncytiotrophoblastic lacunae have fused to form lacunar networks (see Fig. 4-2B), giving the syncytiotrophoblast a spongelike appearance. The lacunar networks, which are particularly prominent around the embryonic pole, are the primordia of the intervillous space of the placenta (see Chapter 8). The endometrial capillaries around the implanted embryo first become congested and dilated to form sinusoids, which are thin-walled ter-minal vessels that are larger than ordinary capillaries. The syncytiotrophoblast then erodes the sinusoids, and maternal blood fl ows into the lacunar networks. The degenerated endometrial stromal cells and glands, together with the maternal 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 Fig. 4-2B). These spaces rapidly fuse to form a large, isolated cavity, the extraembryonic coelom (Fig. 4-3A). This fl uid-filled cavity surrounds the amnion and the umbilical 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 (see Fig. 4-3B). During formation of the secondary umbilical vesicle, a large part of the primary umbilical vesicle is pinched off. The human umbilical vesicle (yolk sac) contains no yolk. It may have a role in the selective transfer of nutritive materials to the embryonic disc. The trophoblast absorbs nutritive fl uid from the lacunar networks in the syncytiotrophoblast; the fl uid is then transferred to the embryo.

A

B

SyncytiotrophoblastAmnion

Lacunarnetwork

Endometrialcapillary

Epiblast

Cytotro-phoblast

Extraembryonicmesoderm

Primaryumbilicalvesicle

Closingplug

Hypoblast

Erodedgland

Maternalblood

Lacunarnetwork

Embryonic disc

Cytotrophoblast

Amnioticcavity

Uterine gland

Extra-embryoniccoelomic space

Extra-embryonicendodermallining of theumbilical vesicle(yolk sac)

FIGURE 4-2. Illustration of sections of two implanted blastocysts at 10 days (A) and 12 days (B). These stages of development are characterized by the formation of lacunar networks—the communication of the blood-filled lacunae. In B, note that spaces have appeared in the extraembryonic mesoderm, indicating the beginning of the formation of the extraembryonic coelom.



■ DEVELOPMENT OF THE CHORIONIC SAC

The end of the second week is characterized by the appearance of primary chorionic villi (Figs. 4-3A and 4-4A and C). Proliferation of the cytotrophoblastic cells produces cellular extensions that grow into the overlying syncytiotrophoblast. The growth of these cytotrophoblastic extensions is believed to be induced by the underlying extraembryonic somatic mesoderm. The cellular projections form primary chorionic villi, the first stage in the development of the chorionic villi of the placenta. The extraembryonic coelom splits the extraembryonic mesoderm into two layers (see Fig. 4-3A and B):• The extraembryonic somatic mesoderm, which lines

the trophoblast and covers the amnion• The extraembryonic splanchnic mesoderm, which surrounds the umbilical vesicle

The extraembryonic somatic mesoderm and the two layers of trophoblast form the chorion. The chorion forms the wall of the chorionic sac (see Fig. 4-3A). The embryo and its amniotic sac and umbilical vesicle are suspended in the chorionic cavity by the connecting stalk (see Figs. 4-3B and 4-4B). The amniotic sac and the umbilical vesicle are analogous to two balloons pressed together (at the site of the embryonic disc) and suspended by a cord (the connecting stalk) from the inside of a larger balloon (the chorionic sac). Transvaginal ultrasonography (endovaginal sonography) is used to measure the diameter of the chorionic (gestational) sac. This measurement is valuable for evaluating early embryonic development and pregnancy outcome.

The 14-day embryo still has the form of a fl at, bilaminar, embryonic disc, but endodermal cells in a localized area are now columnar and form a thickened circular area called the prechordal plate (see Fig. 4-3B and C). This plate indicates the future site of the mouth and is an important organizer of the head region.

■ IMPLANTATION SITES OF THE BLASTOCYST

Implantation of the blastocyst begins at the end of the first embryonic week and normally occurs in the endometrium of the uterus, usually superiorly in the body of the uterus and slightly more often on the posterior than on the anterior wall.

Prechordal plate

A

Maternalsinusoid

Extraembryonicsomatic mesoderm

Lacunarnetwork

Primary chorionic villus

Chorion

Endometrium

Extraembryonicsplanchnic mesoderm

Extraembryoniccoelom

Primaryumbilicalvesicle

B

Maternal blood Primary chorionic villus

Connectingstalk

Prechordalplate

Endometrialepithelium

Secondaryumbilicalvesicle


Remnant of primary umbilicalvesicle

Bilaminar embryonicdisc

HypoblastEpiblastAmnion

C

FIGURE 4-3. Sections of implanted human embryos. A, At 13 days, note the decrease in the relative size of the primary umbilical vesicle and the early appearance of the primary chorionic villi. B, At 14 days, note the newly formed secondary umbilical vesicle and the location of the prechordal plate. C, Detailed view of the prechordal plate area outlined in B.

PLACENTA PREVIA

Implantation of a blastocyst near the internal os (see Fig. 2-2A) results in placenta previa, a placenta that partially or completely covers the os. Placenta previa may cause bleeding because of premature separation of the placenta during pregnancy.


34 ■ Before We Are Born

EXTRAUTERINE IMPLANTATION SITES

Blastocysts may implant outside the uterus. Extrauterine implantations result in ectopic pregnancies; most ectopic implantations occur in the uterine tube (Figs. 2-2B and 4-5A and B). Ectopic tubal pregnancy occurs in approximately 1 in 200 pregnancies in North America. A woman with a tubal pregnancy has the usual signs and symptoms of pregnancy, but she may also experience abdominal pain and tenderness because of distention of the uterine tube, abnormal bleeding, and irritation of the pelvic peritoneum.

There are several causes of tubal pregnancy; how-ever, they are often related to factors that delay or prevent transport of the cleaving zygote to the uterus (e.g., blockage of the uterine tube caused by scarring secondary to infection in the abdominopelvic cavity). Ectopic tubal pregnancies usually result in rupture of the uterine tube and hemorrhage into the peritoneal cavity during the first 8 weeks, followed by death of the embryo. Tubal rupture and hemorrhage constitute a threat to the mother’s life.

INHIBITION OF IMPLANTATION

The administration of relatively large doses of estrogen (“morning-after pills”) for several days, beginning shortly after unprotected sexual intercourse, usually does not prevent fertilization, but often prevents implantation. Normally, the endometrium progresses to the luteal (secretory) phase of the menstrual cycle as the zygote forms, undergoes cleavage, and enters the uterus. A large amount of estrogen, however, disturbs the normal balance between estrogen and progesterone that is necessary to prepare the endometrium for implan-tation. An intrauterine device inserted into the uterus through the vagina and cervix usually interferes with implantation by causing a local infl ammatory reaction. Some intrauterine devices contain slow-release pro-gesterone, which interferes with the development of the endometrium so that implantation does not usually occur.

A

Maternal blood Primary chorionic villus

Cytotrophoblasticcore

Chorionic sac

Chorionic cavityEmbryo

Syncytiotrophoblast

Trophoblasticlacunar network


C

B

FIGURE 4-4. A, Illustration of a section (outlined in B) of the wall of the chorionic sac. B, Illustration of a 14-day conceptus showing the chorionic sac and the chorionic cavity. C, Transverse section through a primary chorionic villus.



CLINICALLY ORIENTED QUESTIONS

1. What is meant by the term implantation bleeding? Is this the same as menses (menstrual fl uid)?

2. Can a drug taken during the first 2 weeks of pregnancy cause abortion of the embryo?

3. Can an ectopic pregnancy occur in a woman who has an intrauterine device?

4. Can a blastocyst that implants in the abdomen develop into a full-term fetus?

5. Can combined intrauterine and ectopic pregnancy occur?

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

Embryo and extraembryonic

membranes

Site of ectopictubal pregnancy

Isthmus

Ampulla

AB

FIGURE 4-5. A, Coronal section of the uterus and the uterine tube illustrating an ectopic pregnancy in the ampulla of the tube. B, Ectopic tubal pregnancy (6 weeks). The sonogram of the uterine tube (left) shows a small gestational sac (arrow). (B, Courtesy of E.A. Lyons, MD, Department of Radiology, Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada.)


the second w of human development - elsevier · conceptus is approximately 0.1 mm. a, illustration...

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