Implantation.

The blastocyst usually implants on the posterior uterine wall. The implantation begins at the end of the first week and is completed by the end of the second week. During the sixth day, the blastocyst attached to the endometrial epithelium. During the second week, the trophoblast begins to differentiate into the syncytiotrophoblast and the cytotrophoblast. Penetration of the blastocyst into the mucosa result from proteolitic enzymes produced by the syncytiotrophoblast. At the beginning of the second week the blastocyst is embedded in the endometrial stroma. The endometrial cells around the early conceptus enlarge and accumulate glycogen and lipids. These cellular changes, together with the vascular and glandular alterations in the endometrium are called the decidual reaction.

Three different regions of the decidua are identified according to the implantation site. The decidua basalis is the portion of the endometrium that underlies the implantation site. The decidua basalis forms a compact layer, called the decidual (basal) plate. The decidua parietalis (vera) includes the remaining endometrium of the uterus and the cervix.

Development of the circulatory system.

The blood vessels and heart first appear as collection of endothelial cells that differentiate from mesenchymal cells. The heart, main blood vessels, and peripheral vessels develop independently and later unite to establish a blood circulation.

Arteries and veins of all types first appear as ordinary capillaries, which later increase in size and acquire smooth muscle and connective tissue by differentiation from the surronding mesenchyme. After the establishment of the circulation, new vessels arise by budding from pre-existing vessels.

The heart in the earliest human embryos is a tube with a double wall: the internal endothelium, from which the endocardium develops, and the external myoepicardial layer. From the myoepicardial layer are formed both myocardium and epicardium. The endocardium has important roles in the formation of partitions to separate the primary single cavity of the heart into chambers, and in the formation of the valves.

There are two opinions concerning the mode of development of the lymphatic vessels. According to one view the lymphatic vessels arise as evaginations or buds from veins. Most observers, however, believe that the lymphatics first arise independently from the veins as isolated intercellular clefts in the mesenchyme. The mesenchymal cells lining the clefts differentiate into endothelial cells, and the clefts enlarge and fuse to form the primary lymphatic vessels. These later establish communication with the veins. Later development of the lymphatic stem occurs mainly by budding from the wall of pre-existing lymphatics in much the same way as in the blood vessels.

Embryonic development of blood cell.

There are three ill-defined phases of hemopoiesis during intrauterine development, and in all phases the initiation of hemopoiesis is the same. It consists of a differentiation of mesenchymal cells into free cells whose cytoplasm acquires a definite basophil character. These cells, often termed, hemocytoblasts, proliferate actively. Such a process occurs initially within the yolk sac during the third week of development. The hemocytoblasts become transformed into primitive erythroblasts by the elaboration and accumulation of hemoglobin within their cytoplasm. They differ from bone marrow-derived erythrocytes in that they are larger and retain their nuclei.

During the second phase, hemopoiesis occurs within the liver and spleen. It commences in the liver at about six weeks and continues actively until the middle of fetal life. Hemocytoblasts proliferate and differentiate into nucleated and non-nucleated red blood cells, leukocytes, and megakaryocytes. The formation of nucleated red blood cells gradually diminishes prior to the middle of fetal life and hemopoietic activity in the liver normally disappears at the time of birth. Hemopoiesis occurs within the spleen between the second and eight months. Erythropoiesis ceases at or just after birth, although lymphocytes continue to be produced within the spleen postnatally. Additionally, during the second phase, the thymus commences to produce lymphocytes from the second month on.

The third phase involves the bone marrow and the lymph nodes. Myeloid tissue of bone marrow appears in the third fetal month when the cartilaginous primordia of the bones become invaded by mesenchyme during the process of ossification. Again mesenchymal cells round off and become hemocytoblasts, which give rise to erythroblasts, myelocytes, monocytes, lymphocytes, and megakaryocytes. With the appearance of bone marrow, production of nucleated red blood cells ceases. Lymph nodes develop relatively late during fetal life, and production of myeloid elements is never a marked feature within them. However, they continue to function throughout life, like the spleen, in the production of lymphocytes.

Development of the lymphoid organs.

Development of the thymus.

In man the thymus arises as a paired ventral outgrowth from the third branchial pouch. Each outgrowth has a narrow lumen at first, but this quickly is obliterated by proliferation of the lining epithelial cells. The epithelial cells differentiate, and some transform into epithelial reticular cells at about the end of the second month of pregnancy. Thymocytes (or lymphocytes) appear at this time also. It is thought that they arise from mesenchymal cells which invade the developing thymus. The lymphocytes proliferate rapidly and the epithelium is converted into a reticular cell mass. Lobules form at this time, and connective tissue invades the lobes to form septa and trabeculae. Hassall’s corpuscles first appear during fetal life and continue to form until involution is initiated. They are thought to arise from hypertrophied and degenerating epithelial cells.

Development of the spleen.

The primordium of the spleen in human embryos appears as a thickening of the mesenchyme in the dorsal mesentery of the stomach during the fifth week of embryonic development. At this time it consists of a mass of mesenchymal cells that later divide actively. The mass of the primordium is added to by apposition of cells from the covering mesothelium of the body cavity. The mesenchymal cells differentiate into cells of the reticulum and into primitive free cells resembling lymphocytes. Later the tissue becomes myeloid in type, containing all stages in the development of megakaryocytes, granulocytes, and erythrocytes. The development of lymphocytes and monocytes continues throughout life, but myeloid elements dissappear shortly after birth.

In the early stages of development, the spleen is supplied by a rich capillary plexus, but as a characteristic distribution of vessels is established, lymphocytes become compactly arranged around the arteries to form the white pulp. Definite nodules do not appear until later in fetal life, and germinal centres are not present until after birth. The venous sinuses develop as irregular spaces that later become connected with the established blood vessels.

Development of the digestive system.

The primitive gut forms during the fourth week of the development as a result of cephalocaudal and lateral folding of the embryo. This endoderm lined cavity is incorporated into the embryo, while the yolk sac and the allantois remain temporarily by outside the embryo.

The endoderm of the primitive gut gives rise to the epithelium and glands of the digestive tract. The muscular and fibrous elements of the digestive tract are derived from the splanchnic mesoderm. The epithelium at the cranial and caudal extremities of the digestive tract is derived from the ectoderm of the stomodeum and the proctodeum (anal pit).

The primitive gut is divided into four parts: a) the pharyngeal gut which extends from the buccopharyngeal (oropharyngeal) membrane to the respiratory (tracheobronchial) diverticulum; b) the foregut, extending from the tracheobronchial diverticulum to the liver outgrowth; c) the midgut, extending from the liver outgrowth to the junction of the right two thirds and left one third of the transverse colon in the adult (posterior intestinal porta); d) the hindgut, extending from the posterior intestinal porta to the cloacal membrane. The liver, biliary apparatus, pancreas and the respiratory system arise as diverticula from the foregut.

Along the entire length the intestinal tube is suspended from the dorsal body wall by a dorsal mesentery. Along the segment of its length, it is attached to the ventral body wall by a ventral mesentery.

Development of the teeth.

Each tooth has a mesodermal and an ectodermal component, the latter forming only the enamel. At five to six weeks, the oral ectoderm develops horseshoe-shaped linear thickening in the upper and lower jaws. These labiodental laminae are at first solid and bifid, extending deeply into underlying mesoderm.The outer labial limb soon splits to form the groove between the lip and the alveolar process of the jaw (the future vestibule) while the inner limb, the dental lamina, develops a series of bud-like thickenings, or tooth germs, numbering five in each half jaw, one for each deciduous tooth. Later, starting at ten to twelve weeks, a second series of tooth germs develops on the lingual side, these numbering eight in each half jaw (five to replace deciduous teeth plus three to form the molars, which are not preceded by a deciduous tooth).

Each epithelial tooth germ, still attached above to the dental lamina by a cord of the cells, is at first “cap”-shaped, but becomes invaginated from below by a mesenchymal papilla to become the “bell stage” or enamel organ, the whole embedded in connective tissue (the dental sac). Soon, this completely invests the developing tooth when the connection to the dental lamina breaks down and disappears. The peripheral part of the enamel organ is formed by a single layer of epithelial cells that are low cuboidal on the convexity of the bell (the outer enamel or dental epithelium) and more columnar in the concavity (the inner enamel or dental epithelium). The two meet at the rim of the bell, the cervical area or neck, this marking the future cementoenamel junction. Internally in the bell, the cells are stellate, separated by intercellular spaces (the stellate reticulum), but form a more regular layer called the stratum intermedium adjacent to the inner enamel epithelium that become the enamel-forming ameloblasts.

By the time the ameloblasts are differentiated, the peripheral mesodermal cells of the dental papilla adjacent to them became arranged in a regular manner, one cell thick, at the odontoblasts, the two separated only by basal lamina material that later breaks down. By about twenty weeks of gestation, hard tissues of the both begin to form. Uncalcified predentin is formed first and increases in thickness by apposition on the internal surface. The predentin extends down towards the neck, and it increases in thickness, cytoplasmic processes of the odontoblasts are formed as the dentinal fibres. The odontoblasts form collagen and matrix, mainly glycosaminoglycans, and calcification then follows in the first-formed matrix, transforming predentin to dentin. Because mineralization occurs after the formation of fibres and ground substance, there always is a thin layer of predentin adjacent to the odontoblasts. Once dentin formation has been initiated, ameloblasts commence to form enamel on the dentin surface. The first enamel formed is seventy per cent minerals and thirty per cent organic matrix, whereas mature enamel is ninety nine per cent minerals. Thus, the matrix is necessary for crystallite deposition and/or orientation, and later it is lost almost completely. With an increase in thickness of the enamel, the ameloblasts recede from the dentin.

At the periphery of the enamel organ in the future neck region, i.e., at the edge of the bell, where inner and outer enamel epithelia come together, a fold of epithelial cells develops and grows downward toward the root. This is the epithelial root sheath (of Hertwig). Root development occurs shortly before tooth eruption and gradually processes as the crown emerges through the gingiva. Odontoblasts develop in relation to the epithelial sheath of Herwig and form dentin. Cementum develops from mesenchyme of the periodontal membrane. The epithelial sheath of Herwig disappears only when the root is formed completely.

During eruption of a permanent tooth, the deciduous tooth superficial to it gradually is resorbed by growth pressure, osteoclasts being prominent during the process. The deciduous tooth when finally shed consists only of the upper portion of the crown, the remainder having been resorbed.

Development of the pancreas.

The pancreas arises from two diverticula, ventral and dorsal, from the junction of foregut and the midgut. The diverticula fuse, the epithelial lining branching to form acini connected to the primary outgrowths by a duct system. Some epithelial buds lose their connection to the duct system and differentiate into islet tissue. However, it has been suggested that some of the islet cell types may arise from cells of the neural crest that migrate into the pancreas early in development. During the development, the duct systems of the two diverticula become interconnected so that although the dorsal diverticulum forms the bulk of the pancreas, its secretion passes to the ventral outgrowth, the duct of which becomes the main pancreatic duct. The proximal part of the duct of the dorsal diverticulum remains as the accessory pancreatic duct, which opens into the duodenum at a higher level than the main duct. The latter has a common opening into the duodenum with the common bile duct from the liver.

Development of the liver.

The liver develops as a ventral diverticulum (endoderm) of the foregut and midgut junction and extends anteriorly into the mesenchyme of the septum transversum. Proliferation of the edodermal cells gives rise to the cords and plates of hepatic cells, which at first are tubular in arrangement with cells arranged around a central lumen. The sinusoids develop from vascular tissue associated with the vitelline veins, which themselves form the portal vein. Mesenchyme associated with the portal vein and that of the septum transversum develops into the connective tissue and capsule of the organ.

The original diverticulum of the gut and its main branches remain tubular as the bile and hepatic ducts. The gallbladder and cystic duct develop as a diverticulum from the main duct.

The liver is one of the main blood-forming organs in the fetus and remains this potentiality in the adult.

Developmen of the skin and its appendages.

The skin consists of the superficial layer, the epidermis, and the deep layer, the dermis. The epidermis is derived from the ectoderm. In the fifth week, the skin of the embryo is covered by simple cuboidal epithelium. By the seventh week, the skin contains single squamous layer (periderm or epitrichium), and a basal layer. During the fourth month, an intermediate layer, containing several cell layers, is interposed between the basal cells and periderm. During the early fetal period the epidermis is invaded by melanoblasts, cells of the neural crest origin. The dermis is derived from the mesenchyme of somatopleura and the dermatomes.

Hair begins to develop during the third month as an epidermal proliferation into the underlying dermis. The epithelial cells of the hair bud give rise to the hair, and the epithelial root sheath. Surrounding mesenchymal cells differentiate into dermal root sheath. Peripheral cells of the epithelial root sheath proliferate to form a sebaceous gland but. Sweat glands develop as downgrowths of epithelial cords into the underlying dermis.

Nails begin to develop at about ten weeks of gestation as thickened areas of the epidermis at the tip of the digits. Later, these nail fields extend to the dorsal surface and become surrounded by the nail folds. Cells from the proximal nail fold grow over the nail field and form keratinized nail plate, the primordium of the nail.

The mammary glands begin to develop during the sixth week as thickened strips on the ectoderm (mammary ridges) that extend from the axillary to the inguinal regions. They regress in most locations except in the area of the pectoral muscle, where they proliferate. The downgrowth of epithelial tissue continues to proliferate into sixteen to twenty-four solid outbudding which dive rise to the lactiferous ducts. Fibrous connective tissue fat of the mammary gland develops from the surrounding mesenchyme. The lactiferous ducts at first open into a small mammary pit.

Development of the respiratory system.

In the embryo, the respiratory system originates as a ventral outgrowth from the floor of the primitive pharynx, the anterior part of the foregut. The outgrowth then extends inferiorly and divides into right and left bronchial buds, each of which undergoes repeated dichotomous branchings. The primary outgrowth becomes the trachea, each bronchial bud a main bronchus, and the orders of branchings the smaller bronchi, bronchioles, and terminal alveoli. Thus, the entire system has a lining which is of endodermal origin, being derived from the lining of the foregut. Respiratory tissue initially has a gland-like appearance of epithelium (endodermis)-lined alveoli embedded in mesoderm. The mesoderm forms the accessory coats of the system, e.g., connective tissue, muscle.

Development of the urogenital system.

The urogenital system can be divided functionally into the urinary (excretory) system and the genital (reproductive) system. Embryologically and anatomically, however, they are closely connected. The urogenital system develops from the intermediate mesoderm which extends along the dorsal body wall of the embryo. The intermediate mesoderm later loses its connection with the somites and forms a longitudinal elevation of the mesoderm called the urogenital ridge. Part of the urogenital ridge giving rise to the urinary tract is known as the nephrogenic cord. Medial part of the urogenital ridge forms the gonadal (genital) ridge. The mesothelial lining of the peritoneal cavity and the endoderm of the urogenital sinus also take part in the development of the urogenital system.

Development of the urinary system.

During development the kidney arises from intermediate mesoderm situated in the posterior abdominal wall. Primitive nephrons develop from the cords of mesenchymal cells and acquire a lumen, and the blind dilated end of the nephron (the future Bowman’s capsule) is invaginated by a tuft of capillaries. The ureteric bud, a diverticulum arising from the mesonephric or wolffian duct, grows into the mass of developing kidney, or metanephros. The mesonephric duct later becomes associated with the genital system, and by differential growth, the ureteric bud originating from it is taken up into the developing urinary bladder. When the growing end of the ureteric bud reaches the metanephros, it undergoes a series of divisions, each terminal branch becoming continuous with a developing nephron. The fine branches of the ureteric bud thus become the various orders of collecting or excretory ducts, and its main branches become the minor and major colyces of the renal pelvis; the ureteric bud itself becomes the ureter. The first nephrons to develop are those in the deeper layers of the cortex. At birth the kidney is irregular in outline (fetal lobulation), and the outer cortical region consists of undifferentiated mesenchyme from which additional nephrons will develop for some months or even years after birth. When development is complete, the kidney outline becomes smooth.

Developmental abnormalities of the kidney and excretory passages are not incommon. Early division of a ureteric bud before it reaches the metanephros can result in conditions such as bifid or double ureter, and double kidney. Failure of individual nephrons to connect with terminal divisions of the ureteric bud results in cysts, usually multiple (multicystic kidney).

Development of the male and female reproductive system.

The primordia of the gonads arise as thickenings of mesodermal epithelium, the genital ridges, on the medial surface of the mesonephros. The epithelial cells of the ridge proliferate and form a band of tissue composed of two types of cells. Most cells are small, cuboidal elements and scattered between them are large, spheroidal cells, the primitive sex cells. The epithelial cells penetrate the underlying mesenchyme and form sex cords.

Sexual differentiation. In the male human embryo, the testis becomes recognizable at about seven weeks. The sex cords become more distinct and elongate to form the seminiferous tubules. Their peripheral ends anastomose and unite with a number of mesonephric tubules to form the rete testis. Prior to the onset of puberty component cells of the seminiferous tubules differentiate into spermatogonia and Sertoli cells.

Differentiation of the ovary does not commence until about the eighth week of gestation. The sex cords formed during the indifferent stage gradually disappear. The covering (germinal) epithelium continues to proliferate and produces the primitive cortex of the ovary. This mass of cortical cells is subdivided by strands of mesenchyme into clusters containing oogonia, probably derived from the primitive sex cells. Proliferation of cortical tissue continues into the latter half of fetal life.

Genital ducts. Genital ducts develop in close connection with the embryonic urinary system. They are laid down initially as two paired longitudinal ducts, the ducts of Wolff and of Mьller, the latter from mesoderm lining the coelomic cavity. In the male the wolffian duct is transformed into ductus epididymidis and ductus deferens. Connection of the ductus epididymidis with the rete testis is established by a number of mesonephric tubules which become the ductuli efferentes. The mьllerian duct involutes, leaving only small rudiments. In the female, the wolffian ducts regress and the mьllerian ducts transform into the female genital ducts. Caudally the two mьllerian ducts fuse to form a single tube which opens into the urogenital sinus (cloaca). The paired upper portions from the fallopian tubes and the unpaired terminal portion become the uterus and vagina.

In man, as in most mammals, the XY and XX sex chromosome complements determine male and female sex, respectively. In the former, the genetic determinant on the Y chromosome is responsible for differentiation of the indifferent gonad into a testis, which otherwise develops as an ovary. The differentiating testis produces substances that suppress mьllerian duct development and promote wolffian duct differentiation. In the absence of a testis, mьllerian ducts differentiate and wolffian ducts fail to undergo differentiation.

Development of the nervous system.

The neural tube is developed from an infolding of the ectoderm along the dorsum of the embryo, from which cells detach to form the neural crests on each side. From neural crests are developed the craniospinal ganglia and perhaps also the autonomic ganglia. The cells of the neural tube, the wall of which at first is composed of a single layer of epithelium, undergo rapid division and differentiate into spongioblasts, which later form neuroglia. Ependima develops from the primitive lining of the neural tube. In the neural crests, differentiation occurs and neurons, satellite cells, and neurolemma are formed. Microglia probably are formed by mesenchymal cells, which enter the central nervous system with the blood vessels.

The central nervous system appears in the middle of the third week of the development as a thickened area of the embryonic ectoderm, the neural plate. Its lateral edges become elevated to form the neural folds, which approach each other and fuse in the middle, thus forming the neural tube.

At the cranial and caudal end of the embryo the neural tube is temporarily open and communicates with the amniotic cavity by the way of the cranial and caudal neuropores. The neural tube differentiates into the central nervous system, consisting of the brain and spinal cord, and the neural crest, which gives rise to the most of the peripheral nervous system. The neural canal becomes the ventricular system of the brain and the central canal of the spinal cord.

Development of the endocrine system.

Development of the hypophysis (pituitary gland.)

The hypophysis arises from two separate sources. One portion arises as an evagination of the ectoderm of the primitive buccal cavity which extends as Rathke’s pouch toward the floor of the diencephalon. The pouch comes in close relationship with a downgrowth, the infundibulum, from the floor of the diencephalon. The pouch comes in close relationship with a downgrowth, the infundibulum, from the floor of the diencephalon. The infundibulum gives rise to the neural stalk and the pars nervosa. Rathke’s pouch loses its attachment to the pharyngeal roof by rupture of its original stalk and develops into the adenohypophysis. The cells of its anterior wall proliferate actively and reduce the lumen of the pouch to a narrow cleft. This proliferation forms the pars distalis and from its upper part cells extend around the neural stalk to form the pars tuberalis. The posterior wall of the original pouch, lying between the residual cleft and the pars nervosa, remains thin and becomes the pars intermedia.

Development of the thyroid gland.

The thyroid gland develops as a median downgrowth of the base of the tongue. The foramen cecum of the adult tongue is a vestige that indicates the site of origin. The thyroglossal duct, which connects the developing gland with the foramen cecum, usually becomes obliterated. Remnants of the duct may give rise to cysts or to the pyramidal lobe, a cranial extension of the isthmus. The thyroid gland may include also derivatives of the branchial pouches, such as the ultimobranchial body.

The primordium of the gland initially is a compact mass of epithelial cells which later splits to form a network of solid cords or plates. These break up into small cellular groups, in each of which a lumen develops. As the lumen enlarges, the cells surrounding it become arranged into a single layer to form the definitive follicle.

Development of the parathyroid gland.

The parathyroid glands develop from the endoderm of the pharyngeal pouches, the superior parathyroids from the third pouch. In their development, the inferior parathyroids are closely associated with the developing thymus and are drawn down with it during its caudal migration. Normally, they migrate only as far as the lower poles of the thyroid gland.

Development of the suprarenal glands.

The cortex of the suprarenal gland develops from epithelium (mesothelium) lining the primitive body cavity (coelom) and the medulla from the neural crest and presumptive autonomic ganglion (sympathochromaffin) tissue.

Questions:

1. What periods is the human embryogenesis divided into?

2. How long does the primary period last?

3. How long does the embryonic period last?

4. How long does the fetal period last?

5. What is progenesis?

6. What structural features is the spermatozoon characterized by?

7. What structural features is the oocyte characterized by?

8. What is fertilization?

9. What is Fragmentation (cleavage)?

10. What is gastrulation?

11. What is embryonic histogenesis?

12. What extraembryonic organs do you know?

13. What structural features is the umbilical cord characterized by?

14. What structural features is the amnion characterized by?

15. What structural features is the allantois characterized by?

16. What structural features is the vitelline sac characterized by?

17. What structural features is the chorion characterized by?

18. What structural features is the human placenta characterized by?