Embryonic Period
The embryonic period is the period of organogenesis during which all the major organs and systems of the body differentiate from germ layer derivatives. Consequently, this is the time of greatest vulnerability to teratogens (including drugs, viruses and radiation) that interfere with development. The major features of external body form also establish at this time and the body grows rapidly.
Major processes during the embryonic period include formation of three germ layers ("gastrulation"), neurulation (formation of the neural tube), notochord and somite formation, and folding (establishment of body form). Gastrulation involves the development of three germ layers (in triploblastic organisms, like the human), formation of the primitive gut, and establishment of axial symmetry. The cardiovascular system is especially precocious and circulation begins early in the fourth week.
With their branchial (pharyngeal) arches and tail, vertebrate embryos look much alike for the first few weeks. The human embryo has less resemblance to other vertebrate embryos after the seventh week when the head begins to look more human and the tail regresses. Folding of the embryo and formation of the brain, heart, pharynx, somites, pharynx, liver, limbs, eyes, ears, and nose also greatly affect the external appearance of the embryo.
Formation of Germ Layers ("Gastrulation")
Primitive Streak
Following implantation, the inner cell mass of the blastocyst begins to differentiate into three primary germ layers, the embryonic tissues that will produce all tissues and organs of the body.
Before implantation, a layer of ectoderm (trophectoderm) already has developed around the blastocoel. The trophectoderm will form a portion of the chorion, one of the fetal membranes. As the blastocyst completes implantation during the second week, the inner cell mass undergoes marked differentiation. Within 8 days after fertilization, the upper layer of cells of the inner cell mass proliferates and produces another fetal membrane called the amnion and a slit-like space, the amniotic (amnionic) cavity, develops between the inner cell mass and the invading trophoblast.
Striking changes occur at about the twelfth day after fertilization. The inner cell mass below the amniotic cavity flattens into an embryonic disc that will form the embryo. At this stage, the embryonic disc consists of an upper ectodermal layer called the epiblast, which is closer to the amniotic cavity, and a lower endodermal layer called the hypoblast that borders the blastocyst cavity; mesodermal cells are scattered external to the embryonic disc.
At about the fourteenth day, epiblastic cells migrate toward and proliferate at the dorsal midline of the embryonic disc (blastodisc), forming a thick linear band of cells called the primitive streak. The primitive streak establishes a structural foundation for morphogenesis along the longitudinal axis of the embryo. Cells of the epiblast continue to proliferate and migrate to the center of the embryonic disc.
The primitive streak lengthens by addition of cells to its caudal end. As the primitive streak elongates, its cranial end enlarges to form the primitive knot. Cells from the primitive knot invaginate through a pit (blastopore). The primitive streak produces loose embryonic connective tissue called mesenchyme (mesoblast). The mesenchymal cells migrate inward (invaginate) and then move laterally and cranially between the epiblast and hypoblast. There they form a new cell layer between the epiblast and hypoblast called intraembryonic mesoderm. These cells establish contact with the extraembryonic mesoderm covering the amnion and yolk sac. Some mesoblastic cells invade the hypoblast and displace most or all of the hypoblastic cells laterally. This new germ layer is the intraembryonic (embryonic) endoderm. The cells that remain in the epiblast create the intraembryonic (embryonic) ectoderm, or neuroectoderm.
After arrival at the primitive streak, the cells migrate to the interior, between the epiblast and hypoblast to form embryonic mesoblast and endoderm. This movement, inaccurately called "gastrulation," produces three distinct embryonic layers with markedly different fates. (The term gastrulation is inappropriate because no "gastrula" is formed.) After this process begins, the upper layer that remains in contact with the amniotic cavity is the ectoderm, the lower hypoblast becomes the endoderm, and the middle intervening layer is mesoderm. These three layers are the primary germ layers. After they appear at the end of the second week, the preembryonic stage is complete and the embryonic stage begins. The mesoderm in the disc soon split into two layers, and the space between the layers becomes the extraembryonic coelom.
Mesenchyme from the primitive streak also differentiates into all the various kinds of connective tissue found in the adult and the mesodermal structures of the head.
The primary germ layers are important because they produce the various cells and tissues of the body. As the embryo develops, the ectodermal cells develop into the nervous system, the outer layer of skin (epidermis) including hair, nails, and skin glands, and portions of the sensory organs. Mesodermal cells form the peritoneum, muscle, bone, reproductive organs, dermis of the skin, blood and other connective tissue. Endodermal cells produce the epithelial lining of the of the digestive tract (digestive organs), respiratory tract (trachea, bronchi, and lungs), the urinary bladder, and the urethra. (See Chapter 3 for additional details.)
Notochordal (Head) Process
Mesenchymal cells that migrate through the blastopore produce a tubular midline structure, the notochordal (head) process that later becomes the notochord. The notochord provides a midline axis to provide support to the embryo and becomes the basis of the embryonic axial skeleton.
As the notochordal process lengthens, the primitive streak shortens. The notochordal process continues to grow cranially between the ectoderm and endoderm until its tip reaches the prochordal plate, the site of the future mouth. The prochordal plate firmly attaches to the overlying ectoderm, forming the oropharyngeal membrane. The oropharyngeal membrane prevents further cranial extension of the notochordal process. The cloacal membrane, the future site of the anus, is at the caudal end of the primitive streak.
Neurulation
The neural plate is initially rather narrow in the cervical region and somewhat wider in the cephalic region of the embryo. It gradually expands toward the primitive streak.
About the 18th day, the neural plate invaginates along its midline axis to form a neural groove with paired elevations on either side of the midline called neural folds. The neural groove between the neural folds deepens. The cranial end of the neural plate markedly expands and will later produce the vesicles of the brain. The more slender part of the neural tube caudal to the large cerebral region will become the spinal cord.
Fusion of the neural folds progresses rapidly toward the head and tail, but the anterior and posterior neuropores remain widely open for a while.
Somite Formation
Late in the third week, thick longitudinal bands of tissue on both sides of the midline produce intraembryonic mesoderm (paraxial mesoderm, or epimere). The intraembryonic mesoderm also organizes into intermediate mesoderm (mesomere—the primordia of the genitourinary system) and lateral plate mesoderm (hypomere—that will produce the somatic and splanchnic linings of the coelomic cavities).
The epimeres become segmented into somites that are the primordia of the axial skeleton (vertebral column, ribs, sternum, and skull), the voluntary muscles of the trunk, and the adjacent dermis of the skin. The appearance of somites is an indication of the metamerism (segmentation) of the body.
The first pair of somites develops a short distance caudal to the cranial end of the notochord. Subsequent pairs form in a craniocaudal sequence. About 38 pairs of somites form during the somite period (days 20 to 30), an average of two or three pairs per day. Eventually 42–44 pairs develop. The numbers of somites are one of the criteria used for determining the age of an embryo. By the time the caudal somites appear, the cranial ones differentiate. Therefore, at no time are all the somites visible.
Folding
Shortly after gastrulation begins, folding and differential growth of the embryonic disc produce a bulge known as the head fold that projects into the amniotic cavity. Similar movements produce a tail fold. The embryo is now physically and developmentally separated from the rest of the blastodisc and the extraembryonic membranes. The embryo now has dorsal and ventral surfaces and left and right sides.
Extraembryonic Membranes, Umbilical Cord, Multiple Pregnancy
While the germ layers are forming many intraembryonic structures and organs, the germ layers also produce a complex system of extraembryonic membranes that extend outside the embryonic body. The extraembryonic membranes include (1) the yolk sac (endoderm and mesoderm), (2) amnion (ectoderm and mesoderm), (3) allantois (endoderm and mesoderm), and (4) chorion (mesoderm and trophoblast). The extraembryonic membranes support embryonic and fetal development by maintaining a stable environment and by providing protection, respiration, excretion, and nutrition of the embryo and, later, the fetus. The placenta, umbilical cord, and extraembryonic membranes separate from the fetus at parturition and are expelled from the uterus as the afterbirth. Despite their importance during prenatal development, the extraembryonic membranes leave few traces in the adult.
When implantation first occurs, the nutrients absorbed by the trophoblast can easily reach the blastodisc by simple diffusion. As the embryo and the trophoblastic complex enlarge, however, the distance that separates the two increases and diffusion can not keep pace with the demands of the developing embryo. The chorion solves this problem, for blood vessels that develop within the mesoderm provide rapid transport between the embryo and trophoblast. Circulation through the chorionic vessels begins early in the third week of development when the heart begins to pump blood.
Amnion
Ectodermal cells spread over the inner surface of the amniotic cavity and mesodermal cells soon follow. The combination of ectoderm and mesoderm produces a thin extraembryonic membrane called the amnion. Amniotic development begins by the eighth day following fertilization, at which time its margin is attached around the free edge of the embryonic disc. The amnion later loosely surrounds the embryo, forming an amniotic sac filled with amniotic fluid. As the embryo and fetus enlarge, the amnion expands and contacts the chorion, increasing the size of the amniotic cavity. As the amniotic sac enlarges during the late embryonic period (about eight weeks), the amnion gradually ensheathes the developing umbilical cord with an epithelial covering.
Amniotic fluid is a buoyant medium that performs four functions for the embryo and fetus. Amniotic fluid (1) permits symmetrical development and growth; (2) cushions and protects by absorbing shocks that the mother may receive; (3) helps maintain constant pressure and temperature; and (4) enables freedom of fetal development, important for musculoskeletal development and blood flow.
Amniotic fluid first forms as an isotonic fluid absorbed from the maternal blood in the endometrium that surrounds the developing embryo. The volume later increases and the concentration changes by urine excreted from the fetus into the amniotic sac. The fetus normally swallows amniotic fluid, which becomes absorbed in the gastrointestinal tract. Amniotic fluid contains cells sloughed from the fetus, placenta, and amniotic sac. All of these cells develop from the same fertilized egg and have the same genetic composition. Thus, many genetic abnormalities can be detected through amniocentesis in which the amniotic fluid is aspirated and the cells obtained are examined.
The amnion usually ruptures naturally or surgically just before birth and the amniotic fluid ("bag of waters") is released.
Yolk sac
The yolk sac is the first extraembryonic membrane to develop. The yolk sac develops from migrating hypoblast cells that spread out around the outer edges of the blastocoel to form a complete pouch (exocoelomic membrane) suspended below the blastodisc. This pouch is visible 10 days after fertilization. As gastrulation continues, mesodermal cells migrate around the endodermal pouch and complete the formation of the yolk sac. Blood vessels soon appear within the mesoderm.
The yolk sac provides the primary or exclusive source of nutrition for the embryo in many species of vertebrates. The human embryo, however, receives its nourishment from the endometrium. The yolk sac in human embryos contains no nutritive yolk and remains small. Nevertheless, the yolk sac in humans is an essential structure during early embryonic development. The yolk sac is attached to the underside of the embryonic disc, where it produces early blood cells for the embryo until the liver develops during the sixth week. The dorsal portion of the yolk sac contributes to formation of the primitive gut. Furthermore, primordial germ cells develop in the wall of the yolk sac and migrate during the fourth week to the developing gonads where they become primitive germ cells (spermatogonia or oogonia).
The stalk of the yolk sac usually separates from the gut by the sixth week, and the yolk sac gradually shrinks as pregnancy advances. During an early stage of development, the yolk sac becomes a very small nonfunctional part of the umbilical cord, and it serves no additional developmental functions.
Allantois
The allantois, a small, vascularized sac of endoderm and mesoderm, forms during the third week as a small outpouching, or diverticulum, of the endoderm near the caudal wall of the yolk sac. The free endodermal tip grows toward the wall of the blastocyst, surrounded by a mass of mesodermal cells.
The allantois remains small but is involved in the formation of blood cells and its blood vessels—the umbilical arteries and vein—serve as connections in the placenta between mother and fetus. The base of the allantois later becomes the urinary bladder.
The extraembryonic segment of the allantois degenerates during the second month, but the intraembryonic portion involutes to form a thick urinary tube called the urachus. After delivery, the urachus becomes a fibrous cord called the median umbilical ligament that attaches to the urinary bladder.
Chorion
The chorion is the highly specialized outermost extraembryonic membrane. The mesoderm associated with the allantois spreads until it completely extends around the inside of the trophoblast (trophectoderm), forming a mesodermal layer beneath the trophoblast. The chorion develops from this combination of trophoblast and associated mesoderm.
Numerous, small, finger-like extensions called villi develop from the chorion and penetrate deeply into the uterine tissue. Initially, villi cover the entire surface of the chorion. Those villi on the surface toward the uterine cavity, however, gradually degenerate and produce a smooth, bare area called the smooth chorion. As this occurs, the villi associated with the uterine wall rapidly increase in number and branch, forming the portion of the chorion called the villous chorion. The villous chorion becomes highly vascular, and as the embryonic heart begins to function, blood is pumped close to the uterine wall.
Thus, the chorion eventually becomes the principal embryonic part of the placenta, the structure through which materials are exchanged between mother and fetus. The amnion also surrounds the embryo and, later, the fetus and eventually fuses to the inner layer of the chorion.
Placenta and Umbilical Cord
The placenta is a vascular structure that provides a vital link between maternal and embryonic systems. The placenta provides respiratory and nutritional support essential for further prenatal development, and it secretes hormones necessary to maintain pregnancy. The placenta forms from maternal and embryonic tissues. The embryonic portion of the placenta consists of the villi of the chorion frondosum; the maternal portion consists of the area of the endometrium called the decidua basalis into which the villi penetrate. Blood does not flow directly between the maternal and embryonic portions of the placenta but, because of the close membranous proximity, certain substances diffuse readily.
The first step in formation of a functional placenta, or placentation, is the appearance of blood vessels in the chorion. By the third week of development, mesoderm extends along the core of each of the trophoblastic villi, forming finger-like projections of the chorion called chorionic villi in contact with maternal tissues. These villi continue to enlarge and branch, forming an intricate network that grows into the decidua basalis of the endometrium. The villi will contain fetal blood vessels of the allantois. Maternal blood vessels continue to erode, and maternal blood slowly percolates through lacunae lined by syncytiotrophoblast. Lacunae fuse into increasingly larger lacunar networks, the primordia of the intervillous spaces of the placenta. Endometrial capillaries dilate into maternal sinusoids. The syncytiotrophoblast erodes some of them, causing maternal blood to seep into the lacunar networks and establish a primitive uteroplacental circulation. Diffusion occurs between the maternal blood flowing through the lacunae and fetal blood flowing through vessels within the chorionic villi.
Initially chorionic villi surround the entire blastocyst. The chorion continues to enlarge within the endometrium. By the fourth week, the embryo, amnion, and yolk sac are suspended within an expansive, fluid-filled chamber. The connection between the embryo and chorion, called the body stalk, contains the distal portions of the allantois and blood vessels that convey blood to and from the placenta. The yolk stalk is the narrow connection between the endoderm of the embryo and the yolk sac.
If implantation occurs, a portion of the endometrium becomes modified as the decidua that includes all but the deepest layer of the endometrium and is shed when the fetus is delivered. Regional differences in placental organization develop as placental expansion forms a prominent bulge in the endometrial surface. The names of the different regions of the decidua, all areas of the stratum functionalis, reflect their positions with respect to the site of the implanted ovum. The decidua capsularis is the relatively thin portion of the endometrium that covers the embryo and separates it from the uterine cavity; this layer does not participate in nutrient exchange and the chorionic villi disappear in this region. Placental functions are now concentrated in a disc-shaped area in the deepest portion of the endometrium called the decidua basalis between the chorion and the stratum basalis of the uterus; the decidua basalis becomes the maternal part of the placenta. The portion of the modified endometrium that lines the entire pregnant uterus, except for the area where the placenta is forming, is the decidua parietalis; the decidua parietalis has no contact with the chorion.
Development of the placenta is completed by the third month of pregnancy. As the end of the first trimester approaches, the fetus moves farther from the placenta, but it remains connected by the umbilical cord, or umbilical stalk, that contains the allantois, placental blood vessels, and yolk stalk.