GASTRULATION. HUMAN HISTO- AND ORGANOGENESIS.
HUMAN EXTRAEMBRYONIC ORGANS
1. Specific processes of embryogenesis.
2. Gastrulation attribute. Manners of gastrulation in vertebrates.
3. Human gastrulation early stage. Manners of germ layers and extraembryonic organs formation.
4. Gastrulation late stage. Formation of the trilaminar embryo.
5. Derivates of the germ layers.
6. Histo- and organogenesis.
7. Amnion, yolk sac, allantois and chorion development sources.
8. Origin, development, structure and functions of yolk sac.
9. Amnion development, structure and functions.
10. Allantois development, structure and functions.
11. Chorion formation, primary and secondary villi, their morphological peculiarities.
12. Umbilical cord origin and structure.
13. Trophoblast origin, structure and functions.
14. Human chorion histophysyology.
15. Placents types. Human placenta, its morphological characteristic and functions.
16. The structure of fetal placenta.
17. Uterine decidual tunics.
18. Maternal placenta structure.
19. Structural compounds of haemochorial barrier.
20. Critical periods of human ontogenesis.
The basic processes of embryogenesis
During the course of embryogenesis some specific processes occur which result in appearance of different embryonic structures. Ooplasmatic segregation – redistribution of the oocyte cytoplasm components which result in formation of presumptive zones (portions of an oocyte from which some exact structure (tissues, organs may develop).
From the fertilized egg (zygote) multicellular organism is developing. In the zygote genes are repressed (inactive) and are in the form of heterochromatin . Heterochromatin – a repressed genetic material (DNA chromosomal protein bound histones). Start of development is characterized by expression ( activation ) of certain groups of genes that dismissal of DNA from histones associated with it. Euchromatin – is expressed (functioning) genes. At first are derepressed genes that cause an increase in cell number (proliferation) and regulate general cell metabolism. Specifical genes for tissues are activated in the stage of gastrulation. In the process of organo- -and histogenesis the other genes are included that regulate a specific function of differentiated cells.
Zygote has the possibility to form a whole body. Some cells which appear as a result of first few divisions after fertilization retain this ability. These cells are called totypotential. With the growth of the cells they gradually lose their ability to form all types of cells that are present in the adult body. When cells are developing they loose some possibilities. This reduction of choises is called determination. Determination – a process in which a group of cells selects only one of many possible ways of development. Gene expression lies in base of determination as a result of this cell (or group of cells) becames a specialized cell type.
Differentiation is the outward manifestation of determination which is accompanied by a gradual restriction of potencies in cell . Differentiation is the morphological and functional expression of the part of the genom, which remained in the possession of a cell or group of cells. As a result of differentiation, some cells acquire new properties (specialized) , but also lose some of its previous capacity. For example, functional differentiation is seen as developing the ability to contractions in myocytes or conductivity in neurocytes .
From the morphological point of view the final differentiation resulting in the formation of numerous specialized cells and structures. Thus, the difference between the cells that have the same set of genes is determined by differentiated repression and expression of genes. Different cell types express different genes.
Due to the fact that protein synthesis is dictated by the expression of genes , the genes are divided into two categories. Genes of the first – operate in all body cells , determining their basic metabolism and insensitive to the direct effects that cause differentiation. Genes of second group are controlling the synthesis of proteins that define the difference between cells during development ( their specialization ) and responding to factors that induce differentiation (inductors).
The question is, what is the reason of expression and repression of different genes? In cleavage of zygote daughter cells receive identical sets of chromosomes (46 for humans ), but not always cytoplasm is divided evenly between daughter cells either in quantity or in quality. It is known that the unequal distribution of different parts of the fertilized egg cytoplasm between daughter cells leads to differentiation of the latter into cells of various types. Thus, the cytoplasm activizes mechanism that makes the impact on the nucleus for inclusion (expression) of some and exclusion (repression) of other genes. In multicellular organism cells are interacting and make influence one to another, this special influence which results in appearance of some new features (possibilities) of affected cells is known as induction. After such influence possibility of cells development will be partially limited (commited). So, the future of cell is determined in exact way.
An essential feature of differentiation is that the differentiation of cells usually occurs after their proliferation. Cells that are dividing quickly are nondifferentiated (e.g. mesenchymal cells). In contrast, highly differentiated cells usually lose their ability to proliferate (e.g. neurocytes , cardiomyocytes, red blood cells ).
Differentiation is irreversible and unidirectional – from less differentiated to more differentiated structure.
Morphogenesis – the embodiment of the spatial plan of the embryo. Morphogenesis is the implementation of various processes: growth, induction of directed cell migration , cell-cell interactions, cell death.
Growth – increase in mass and linear dimensions by increase of cells amount, morphofunctional units of organs, organs and organ systems. The increase in mass without cell division observed in hypertrophy iormal (hypertrophy of the myometrium during pregnancy) and pathological conditions. The body produced numerous humoral factors (growth factors) that stimulate the growth and proliferation of various cell types.
Specific cell types that emerged as a result of the determination, are forming the tissue. The process in which individual tissues during differentiation acquire their characteristic appearance called histogenesis. Organs originate of the various tissue cells. Induction is an important process of organogenesis. Induction means the influence of one embryo tissue (inductor) to another target tissue, resulting in the formation of qualitatively new structure. Examples of primary embryonic induction is the formation of the nervous system of the dorsal ectoderm under the influence of the inductor – chordomezoderm. Hans Shpemana for the discovery of organizer and the phenomenon of primary embriological induction in 1935 won the Nobel Prize. All subsequent induction processes in the embryo are called secondary induction.
Repeated movement or migration of individual or groups of cells from one part to another areb typical for the development of embryo. Often embryonic cells appear and multiply in one place, and differentiate and make their function in another (eg gonoblasts are formed in the yolk sac and migrate to the testes and ovaries, neural crest cells migrate and differentiate into melanocytes of epidermis, adrenal chromaffin cells, neurocytes of autonomic and spinal ganglia and so on).
The concept of positional information explains the nature of cellular interactions in morphogenesis. The overall plan structure of the body is determined very early in the embryonic development. Later, during the whole period of the formation of a body or body parts, morphogenesis specified by positional information signals. Due to this concept, the cell knows its place in the body and differentiates in accordance with this provision. Cell receives positional information from other cells. Moreover, the cell reaches the final differentiation in the case of receiving of series of consecutive signals of positional information. The field within which positional information signals are well working, is called morphogenetic field. During the next several divisions, cells of morphogenetic fields keep the memory of their initial appointment.
The death of cells – a necessary component of embryonic development. Natural (geneticically programmed) cell death during the early stages of ontogenesis is realized by apoptosis. For example , from 25% to 75 % of the total population of neuroblasts are dying at different stages of nerve system development
Gastrulation
Gastrulation is a process of bilaminar and trilaminar disc formation; it is the next stage of embryogenesis after cleavage. Complex process of chemical and morfogenetic-transformations is underlying gastrulation. It is accompanied by reproduction, growth, controlled movement and differentiation of cells.
Gastrulation occurs in the human embryo in the course of implantation and lasts from 7th till 17th day. There are two stages of implantation: early (7-14 days) and late (14-17 days). As a result of first one two germ layers appear – ectoderm and endoderm). The third layer – mesoderm is developing during the late gastrulation.
The type of gastrulation directly depends on the type of oocyte and cleavage. That’s why there are such 4 types of early gastrulation: invagination, epyboli, migration and delamination.
1. Invagination may be observed as a result of full equal synchronic cleavage of lancet and lower chordate zygotes which are developed from olygolecital I isolecital (miolecital) oocytes. Because of active cells prolipheration the vegetative pole of blastula “moves” in direction to the roof obliterating the blastocoele. Such new structure contains two laminas in the wall (outer – ectoderm and inner – endoderm) and new cavity – gastrocoele – inside. Blastopor is the circular opening which connects the gastrocoele with outer space. It has 4 lips: dorsal, ventral, and two lateral ones. This method Gastrulation characteristic Amphioxus, echinoderms and lower chordates. This method of gastrulation is typical for Amphioxus, echinoderms and lower chordates.
2. Epyboly – the other type of gastrulation – is characteristic feature of amphibian (f.e. frog) embryogenesis. Zygote which is developing from the moderate polylecital (medialecital) ovum has full unequal asynchronic cleavage. Because of yolk inclusions, blastomeres are dividing at a different time: some – faster (with less yolk inclusions), some – slower (with a lot of inclusions). So, there are two different groups of cells in cleavage. The cells of the roof of amphiblastula are dividing quicker then the cells of the bottom which contain much yolk inclusions. That’s why it seems that these smaller cells of animal pole “move” over the larger ones (overgrow them) and cower them thus producing two germ layers in such way. Outer layer – ectoderm, inner layer – endoderm. Blastopore of such type of blastula has different lips. Two lateral ones are identical, dorsal one has small cels and ventral lip contains large cells.
Types of early gastrulation: invagination. In invagination blastomeres of vegetative pole of blastula “moves” to animal pole. So, bilayered gastrula now has outer layer – ectoderm and inner one – endoderm.
Types of early gastrulation: epiboly. In the case of epiboly blastomeres of vegetative pole are overpacked with yolk inclusions, blastomeres of animal pole are smaller, dividing faster due to this they move over larger ones. This process of overgrowing is termed “epiboly”.
3. Migration takes place in periblastula. Blastoderm of periblastula consists of similar cells.Some cells of the blastula wall move inside into the blastocell, then they begin to connect thus producing new germ layer inside (entoderm). This type of gastrulation may be seen in birds and reptiles whose oocytes contain much inclusions.
There is uni- and multipolar migration. In the first one blastomeres migrate from one exact place of blasoderm. In the second one blastomeres migrate from different portions of blastoderm. Blastomeres which lie in blastocele produce the endoderm and others which stay where they were form the external layer – ectoderm.
Types of early gastrulation: migration.
Cells are seprating from blastoderm and move to blastocoele. Migration may occure from one place of blastoderm or from many places.
4. Delamination means tangential splitting of blastomers into two layers – superficial ectoderm and deeper endoderm. Such gastrulation occurs in birds and higher Vertebrata. In such case the embryo looks like a shield – embryonic disc. In birds it lies on the yolk surface, in human embryo it is a place of amniotic and yolk sac junction.
Types of early gastrulation: delamination.
Gastrulation of some vertebrates may combine two or three types of gastrulation but with predominance of one of them.
Gastrulation later stage results in trilaminar disc formation. Such embryo has ectoderm, mesoderm and endoderm. It is possible due to such three principle mechanisms as enterocoelic, teloblastic and by means of primitive streak.
1. Enterocoelic type of later gastrulation occurs in blastula which was formed from the primary isolecital oocyte and undergone the full equal synchronic cleavage and invagination in the early gastrulation.
Cross section of lancet embryo in Gastrulation (from I. Stanek)
1- primary intestine, 2 – ectoderm, 3 – endoderm, 4 – mesoderm (stripped), 5 – notochord, 6 – nerve plate or tube, 7 – coelomic cavity, 8 – intestine, 9 – primary segments, 10 – myotom, 11 – myocoele, 12 – skin plate, 13 – ventral mesoderm, 14 – vein, 15 – visceral splanchnotom layer, 16 – parietal splanchnotom layer, 17 – mesoderm lateral plate, 18 – splanchnocoele.
Formation of axial organs and third germ layer – mesoderm begins after appearance of two germ layers. This is next stage of gastrulation – late gastrtulation.
Nerve plate in lancet is developing in dorsal part of ectoderm, later it is producing nerve groove. It peripheral portions move up and form the nerve toruli, later they fuse and nerve tube originate. It lies under ectoderm which is renewing over the surface. Hordomesodermal plate originates in opposite direction and form tube at first and then cord.
So, nerve tube and notochord originate from dorsal lip of blastopore, but nerve plate is developing from primari ectoderm and notochord from primary endoderm.
Mesoderm in such case originates from small cells which lie in marginal zone. These cells evaginate in blastocoele between ectoderm and endoderm in dorsal direction parallely to notochord. At first these pouches are connected with gastrocoele but then they separate and form two closed folds which lie along the embrio axis between primary ectoderm and primary endoderm. These cords of small cells constitute middle germ layer – mesoderm.
This is enterocoelic type of mesoderm formation.
2. Teloblastic type of late gastrulation takes place in amphiblastula which was formed from the moderate telolecital oocyte. In early gastrulation two germ layers are developing by combination of epyboly with invagination (epiboly predominates), in late gastrulation group of small cells from the lateral lips of blastopore are growing between the ectoderm and endoderm near the notochord. These cells are known as “teloblasts” and their reproduction result in the mesoderm development.
3. Migration with primitive streak formation is the most difficult process of mesoderm appearance. The cell of the germ disc are moving from cranial to the caudal part of an embryo and then return back together making the primitive streak and primitive node with a small pit (similar to blastopore). Through this pit some cells migrate between the ectoderm and entoderm. Thus notochord appears from the anterior lip and mesoderm components from posterior one and primitive streak cells.
Early gastrulation of bird embryo is characterized by delamination of blastodisc which is accompanied with migration. In late gastrulation embryonic disc is enlarging very much, it contains embryonic plate in the middle. Peripheral part of disc constitute extraembryonic material.
Light field arround embryonic disc consists of cells which are separated from yolk by subembryonic space. Dark field occupies peripheral part of discoblastula and consists of cells which are closely attached to the yolk. Cells of embryonic disc undergo complex migration.
Cells are especially actively dividing in the cranial part of disc and begin to move in caudal direction in the periphery of disc. Both streams of cells meat at the center and caudal part of embryo, they fuse and move toward in the middle. This cord of cells is termed primitive streak later it forms groove. Primary node (Hensen’s node) appear at the cranial end of primitive streak. Some blastomeres which lie before anterior part of node move back and through primitive pit down thus producing notochord. The last one grow toward between ecto- and endoderm.
Mesoderm, the third germ layer, has no proper laminar structure. It consists of such principle components as somits, nephrogonotom and splanchnotom with parietal and visceral sheet.
Embryo at the stage of primitive streak formation (surface wiev).
1 – primitive streak, 2 – epyblast, 3 – hypoblast, 4 – mesoderm.
The scheme of cellular material movement in embryonic disk of bird at the stage of axial organs formation ( A.H.Knorre ). A – primive streak and primary nodule formation, B – formation of hordomezodermal germ , 1 – ectoderm, 2 – the material of the future neural plate, 3 – material of future notochord, 4 – primary (Hensen) nodule , 5 – the primary pit, 6 – primive streak, 7 – primary furrow, 8 – notochord, 9 – mesoderm . The solid arrows show the direction of movement of material within the outer as well – dotted – within the middle germ layers.
Germ layers differentiation. Mesenchyme
Three germ layers (ectoderm, endoderm and mesoderm) give rise to different tissues, this process is termed histogenesis. Embryonic histogenesis means process of tissues appearances (epithelial, connective, muscular and nerve) from undifferentiated cells of embryonic sources. Tissues interaction results in production of organs (organogenesis).
Embryonic histogenesis is complicated process which is based upon cells division, growth, migration, structural and functional differentiation, cells interaction and dying.
There are four principle stages of differentiation:
1 – ootypic which takes place in fertilized oocyte. Active redistribution of cytoplasmic material of zygote (ooplasmic segregation) occures resulting in presumptive zones formation – these are cytoplasm portions which will produce exact structures of embryo in the future.
2 – blastomers differentiation showes differences of blastomeres at the early stages (e.g.. blastocyst has trophoblast and embryoblast).
3 – embryonic differentiation gives germ layers during gastrulation (ectoderm, endoderm and mesoderm).
4 – histogenetic – produces tissues.
Dorsal part of mesoderm at first is dividing in somits, beginning with cranial part. Each somit consists of dermatom (source of skin connective tissue), sclerotom (chondroid and bony tissue source) and myotom (embryonic source of sceletal muscles).
Intermediate part of mesoderm – nephrogonotome or segmented feet produces transitional epithelium of kidney (urothelium) and gonads (germinal epithelium).
Ventral mesoderm – splanchnotome – is splitting into parietal and visceral plates which surround coelomic space. Visceral splanchnotome layer coveres inner organs and parietal one lies arround them ower the thorax, pericardium and abdominal cavity.
Axial organs formation in chiken embryo (according to A.G.Knorre).
1 — nerve tube, 2 — ectoderm, 3 — notochord, 4 — mesoderm somites, 5 — splanchnotome visceral layer, 6 — splanchnotome parietal layer, 7 — intestinal endodrm.
Mesenchyme originates in the early stages of embryogenesis as embryonic connective tissue, it consists of cells with processes which fill spaces between germ layers. Mesenchymal cells mainly migrate from mesoderm, nevertheless, in vertebrates ectoderm and mesoderm participate in ecto- and endomesenchyme development.
Each embryonic layer differentiate in exact direction producing adequate structures.
Early gastrulation
biologic significance – ectoderm and endoderm formation
|
Type of gastrulation |
Represen-tatives |
Type of ovum |
Cleavage |
Type of gastrulation |
|
Invagination |
Lancet |
Oligolecital I isolecital |
Full equal synchronic |
Celoblastula |
|
Epiboly |
Amphibian |
Medialecital |
Full unequal asynchronic |
Amphiblastula |
|
Delamination |
Insects |
Polilecital |
Superfitial |
Periblastula |
|
Migration |
Birds |
Polilecital |
Meroblastic |
Discoblastula |
Late gastrulation
biologic significance –mesoderm formation
|
Type of late gastrulation |
Early gastrulation |
Source of mesoderm development |
Mechanism |
|
Enterocoelic |
Invagination |
Endoderm |
Invagination |
|
Teloblastic |
Epiboly |
Teloblasts of lateral lips of blastopore |
Cells migration |
|
Migration with primitive streak formation |
Migration and delamination |
Ectoderm |
Cells migration |
Gastrulation of human embryo
Human embryo gastrulation has some peculiarities. During the second week of development, the human blastocyst becomes furmly embedded in the uterine mucosa, and the trophoblast and embryoblast begin their specific development.
At the eighth day of development, the blastocyst is partially embedded in the endometrial stroma. In the area over the embryoblast, the trophoblast has differentiated into two layers: an inner layer of mononucleated cells, the cytotrophoblast, and an outer multinucleated zone without distinct cell boundaries, the syncytiotrophoblast.
1 – embryoblast, 2 – hypoblast, 3 coelomic cavity.
Mitotic figures are found in the cytotrophoblast but not in the syncytiotrophoblast. Thus, cells in the cytotrophoblast divide and migrate into the syncytiotrophoblast, where they fuse and lose their individual cell membranes. Cells of the inner cell mass or embryoblast also differentiate into two layers: a layer of small cuboidal cells adjacent to the blastocyst cavity, known as the hypoblast layer, and a layer of high columnar cells adjacent to the amniotic cavity, the epiblast layer.
Together, the layers form a flat disc. At the same time, a small cavity appears within the epiblast. This cavity enlarges to become the amniotic cavity.
Hypoblast is primary endoderm – produces only extraembryonic endoderm. Actively deviding cells move to the inner surface of trophoblast and are producing wall of yolk sac.
Epiblast is primary ectoderm, in the future it produces embryo and extraembryonic ectoderm.
The trophoblast penetrates continuously deeper into the endometrium, thereby differentiating into the syncytiotrophoblast and the cytotrophoblast; the cells of the embryoblast form the ectodermal and endodermal germ layers, the two layers which constitute the bilaminar germ disc. Such structure consists of epyblast or primary ectoderm (upper layer) and hypoblast or primary endoderm (lower layer).
The cells of ectodermal layers are initially firmly attached to the cytotrophoblast, but with further development small clefts appear between the two layers. These clefts subsiquently coalesce, thus forming a cavity known as amniotic cavity (lies in epiblast). The hypoblast cells are dividing move down then fuse together thus forming the yolk sac.
The proper germ disk consists of amniotic sac bottom cells (upper layer) and yolk sac roof ones (lower layer). All the other cells belong to so called extraembryonic material. So, wall of amniotic sac consists of extraembryonic ectoderm and wall of yolk sac consists of extraembryonic endoderm.
At the 8th day of embryogenesis extraembryonic mesoderm appears in the germ disc (marked with pointers) in the middle part which is known as primitive streak. It lies between ectoderm and endoderm. Mesodermal cells migrate from germ disc outside and produce parietal sheet which underlies the trophoblast and visceral one covering amniotic and yolk sac.
2 – hypoblast, 3 – coelomic cavity, 4 – epiblast, 6 – amniotic cavity.
Epiblast cells adjacent to the cytotrophoblast are called amnioblasts; together with the rest of the epiblast, they line the amniotic cavity. The endometrial stroma adjacent to the implantation site is edematous and highly vascular. The large, tortuous glands secrete abundant glycogen and mucus.
At the 9th day the blastocyst is more deeply embedded in the endometrium, and the penetration defect in the surface epithelium is closed by a fibrin coagulum. The trophoblast shows considerable progress in development, particularly at the embryonic pole, where vacuoles appear in the syncytium. When these vacuoles fuse, they form large lacunae, and this phase of trophoblast development is thus known as the lacunar stage.
9th day embryo; 2 — hypoblast, 4 — epiblast, 5 — trophoblast,
6 — amnion, 7 — syncytiotrophoblast.
At the abembryonic pole, meanwhile, flattened cells probably originating from the hypoblast form a thin membrane, the exocoelomic (Heuser’s) membrane, that lines the inner surface of the cytotrophoblast . This membrane, together with the hypoblast, forms the lining of the exocoelomic cavity, or primitive yolk sac.
By the 11th to 12th day of development, the blastocyst is completely embedded
in the endometrial stroma, and the surface epithelium almost entirely covers the original defect in the uterine wall. The blastocyst now produces a slight protrusion into the lumen of the uterus. The trophoblast is characterized by lacunar spaces in the syncytium that form an intercommunicating network. This network is particularly evident at the embryonic pole; at the abembryonic pole, the trophoblast still consists mainly of cytotrophoblastic cells.
Concurrently, cells of the syncytiotrophoblast penetrate deeper into the stroma and erode the endothelial lining of the maternal capillaries. These capillaries, which are congested and dilated, are known as sinusoids. The syncytial lacunae become continuous with the sinusoids and maternal blood enters the lacunar syste. As the trophoblast continues to erode more and more sinusoids, maternal blood begins to flow through the trophoblastic system, establishing the uteroplacental circulation.
In the meantime, a new population of cells appears between the inner surface of the cytotrophoblast and the outer surface of the exocoelomic cavity.
Fully implanted 12-day human blastocyst. Note maternal blood cells in the lacunae, the exocoelomic membrane lining the primitive yolk sac, and the hypoblast and epiblast cavity. These cells, derived from yolk sac cells, form a fine, loose connective tissue, the extraembryonic mesoderm, which eventually fills all of the space between the trophoblast externally and the amnion and
exocoelomic membrane internally.
Soon, large cavities develop in the extraembryonic mesoderm, and when these become confluent, they form a new space known as the extraembryonic coelom, or chorionic cavity. This space surrounds the primitive yolk sac and amniotic cavity except where the germ disc is connected to the trophoblast by the connecting stalk. The extraembryonic mesoderm lining the cytotrophoblast and amnion is called the extraembryonic somatopleuric mesoderm; the lining covering the yolk sac is known as the extraembryonic splanchnopleuric mesoderm.
Growth of the bilaminar disc is relatively slowcompared with that of the trophoblast; consequently, the disc remains very small (0.1–0.2 mm). Cells of the endometrium, meanwhile, become polyhedral and loaded with glycogen and lipids; intercellular spaces are filled with extravasate, and the tissue is edematous. These changes, known as the decidual reaction.
At 13th day in human blastocyst trophoblastic lacunae are present at the embryonic as well as the abembryonic pole, and the uteroplacental circulation has begun. Note the primary villi and the extraembryonic coelom or chorionic cavity. The secondary yolk sac is entirely lined with endoderm. area immediately surrounding the implantation site but soon occur throughout the endometrium.
By the 13th day of development, the surface defect in the endometrium has usually healed. Occasionally, however, bleeding occurs at the implantation site as a result of increased blood flow into the lacunar spaces. Because this bleeding occurs near the 28th day of the menstrual cycle, it may be confused with normal menstrual bleeding and, therefore, cause inaccuracy in determining the expected delivery date. The trophoblast is characterized by villous structures. Cells of the cytotrophoblast proliferate locally and penetrate into the syncytiotrophoblast, forming cellular columns surrounded by syncytium. Cellular columns with the syncytial covering are known as primary villi.
In the meantime, the hypoblast produces additional cells that migrate along the inside of the exocoelomic membrane. These cells proliferate and gradually form a new cavity within the exocoelomic cavity. This new cavity is known as the secondary yolk sac or definitive yolk sac. This yolk sac is much smaller than the original exocoelomic cavity, or primitive yolk sac. During its formation, large portions of the exocoelomic cavity are pinched off. These portions are represented by exocoelomic cysts, which are often found in the extraembryonic coelom or chorionic cavity. Meanwhile, the extraembryonic coelom expands and forms a large cavity, the chorionic cavity. The extraembryonic mesoderm lining the inside of the cytotrophoblast is then known as the chorionic plate. The only place where extraembryonic mesoderm traverses the chorionic cavity is in the connecting stalk. With development of blood vessels, the stalk becomes the umbilical cord.
Till 13-14th day the embryo looks like two vesicles inside the exocoelomic cavity connecting with trophoblast by “amniotic foot” (connecting stalk).
On the 14th day of embryogenesis human embryo lies inside the endomethrium and the surface defect has usually healed. The trophoblast shows further organization, particularly at the embryonic pole. The syncytial trabeculae become arranged in such a manner that they radiate out from the cytotrophoblast. Cytotrophoblast cells, meanwhile, grow into the core of the syncytial trabeculae, which then are known as primary stem villi. The endodermal germ layer continues to proliferate and the newly formed cells gradually line a new cavity known as the yolk sac. There is an extraembryonic (chorionic cavity) – previous blastocele.
Blue coloured amniotic sac, yellow – yolk sac, greenish – trofoblast.
The germ disc is represented here by two apposed cell discs, the embryinic ectodermal germ layer, which forms the floor of the continuously expanding amniotic cavity, and the extraembryonic endodermai germ layer which forms the roof of the yolk sac. In further development the body of embryo will appears hi the first one.
Next three days trilaminar embryo is developed in germ disc by means of primitive streak formation.
The period from 17th till 20th day is presomit period, when embryo body is separating from extraembryonic organs. The embryonic disc begins to bulge up into the amniotic cavity and shows a marked folding in cephalo-caudal direction. This folding is most pronounced in the regions of head and tail, where so-called head fold and tail fold are formed.
At the beginning of the third week of development , the ectodermal germ layer has the shape of a flat disc which in cephalic region is somewhat broader than caudally. Simultaniously with the formation of the notochord, and in all probability under its inductive influence, the ectodermal disc changes in form and gives rise to the central nervous system.
Initially the nervous system appears as a round to oval thickening of ectoderm in the cephalic region of the embryo. By the end of the third week, however, it has an elongated, slipper-shaped form, the neural plate, which gradually expands in the direction of the primitive streak. During the next few days the lateral edges of the neural plate become more elevated to form the neural folds. As a result of their fusion a tube-like structure, the neural tube, is formed.
Neurulation and formation of somites
Germ layers appear as a result of gastrulation, their components are influencing each other, inducing the formation of new structures. Example : primary (neural) embryonic induction results in the formation of the dorsal ectoderm of the neural tube.
Neurulation- the process of formation of the neural tube . It starts from the 16th day and ending up 22nd – 23rd day.
Stages of neurulation:
1. The formation of the nervous plate in dorsal ectoderm under the influence of the inductor – hordomezoderm;
2. The formation of neural groove;
3. The appearance of the nerve crests;
4. Formation of neural crest and cells migration form here;
5. neural crests fusion and the formation of the neural tube;
6. Closing of the ectoderm over the neural tube.
On the 20th day of embryonic development somit period begins. Dorsal mesoderm germ areas are divided into individual segments that lie on either side of the notochord – somites .
Formation of somites starts from the cranial to the caudal end of the embryo parallely with regression of Henzen nodule. New pair of somites is formed behind the latter one after a certain period of time. This interval is an average of 6.6 hours. Somite has cavity bounded by cells which are linked by tight junctions . Each somite has sklerotom, dermatom and myotom, their cells have their migration routes and serve as a source for a variety of structures.
Formation of somit and subsequent migration of cells . Left – mezodermal cells are concentrated lateraly to the neural groove around a small cavity on the right – cells of ventral and medial part of somit begin to migrate in the direction of the notochord, these cells belong to sklerotom .
Sklerotom. Under the influence of the notochord and neural tube cells of ventromedial part of somites (sklerotom ) multiply rapidly and migrate from somit, surrounding notchord and ventral part of neural tube. Evicted cells differentiate and form cartilage in the vertebrae, ribs and shoulder blades .
Miotom and dermatom. Myotom is allocated in the dorsolateral part of the somit (inner layer of cells that eventually forms a skeletal muscle) and dermatom (outer layer producing skin connective tissue).
On the 22nd day of development the embryo has 7 pairs of segments , and on the 35th day – 43 – 44 – pairs.
The lateral mesoderm is not segmented and split into parietal (dorsal) and visceral (ventral) layer of splanchnotome. A small area of mesoderm that links somites and splanchnotome is called nephrogonotom which formes then the urinary and reproductive systems.
Neurulation and differentiation of mesoderm lasts till the 4th week of embryogenesis resulting in formation of tissues. Histogenesis is parallel to organogenesis and systemogeneis, but the process of their growth and development continues in fetal and postnatal periods .
Organogenesis. On the 4th week active formation of organs begin – organogenesis. At this stage there are the conception of limbs and the basic organ systems, but the process of growth and development continues in the fetal and postnatal periods. According to the clonal theory, any tissues and organs originate from a small group of clones, each of which is formed from its stem cells. For example, photoreceptor cells are formed in both eyes of 20 clones, proximal tubules of the kidneys come from 4-5 cells. In the early stages of development mesoderm plays an important role in a general plan of the body. It serves as a carrier of positional information. Crucial in organogenesis with induction interaction between cells.
Formation of whole organ is in the complex morphogenetic processes , which in turn are based on molecular genetic events. Molecular morphogenetic system еake part in this formation of a body. They are activized by several or even one gene. Activation of these genes leads to the inclusion in tissue specific syntheses that determine the specificity of theorgan.
Human embryo early embryogenesis peculiarities.
1. Full subequal asynchronic cleavage.
2. Forestall development of extraembryonic organs.
3. Embryo implantation into endometrium and placenta formation.
4. All three germ layers are formed from primary ectoderm.
Early gastrulation 7th -14th days
1. Embryoblast delaminates into epiblast and hypoblast.
2. Amnion originate from epiblast (primary ectoderm).
3. Yolk sac – from hypoblast (primary endoderm).
4. Trophoblast differentiates into cytotrophoblast and syncytiotrophoblast.
5. Embryonic disc – the attachment of amniotic sac bottom and the roof of yolk sac.
6. Embryo’s body has one layer – the amniotic sac bottom.
Late gastrulation 14th-17th days.
1. Migration with primitive streak formation.
2. Extraembryonic mesoderm migrate from embryonic disc.
3. Three layers of embryo body are formed at the same time from embryonic ectoderm.
Extraembryonic or provisional organs
In different stages of embryogenesis embryo has different types of nutririon. During the first 30 hours after fertilization it posseses nutritive substances from the yolk inclusions of the oocyte. It is so called “vitelotrophic nutrition” (vitelum – from
At the begining of the 5th week trophoblast enzymes solve the wall of uterine mucosa vessels and new type of nutrition begins. It is “hematotrophic nutrition”, because the embryo receives all the necessary products from the mother blood.
As were told before, in the course of human embryogenesis early stages some temporary organs appear to supply the normal life, growth and development of proper embryo. They are so-called extraembryonic or provisional organs.
1. Amnion
2. Yolk sac
3. Umbilical cord
4. Allantois
5. Chorion
6. Placenta
At first yolk sac like a provisional organ arises in fishes. Then in animals amnion, serous tunic, alllantois, chorion, placenta and umbilical cord were developed.
Because of intrauterine development extraembryonic organs in mammalians are forming much earlier then in birds. At the stage of blastocyst trophoblast appears and forms the chorion. The last one introduce itself into endomethrium thus forming the fetal portion of placenta.
Human EXTRAEMBRYONIC ORGANS
|
Organ |
Appearance and existence |
Origin |
Structure |
Functions |
|
Amnion |
3rd week-delivery |
Epiblast |
Epithelium (extraembryonic ectoderm) and connective tissue (extraembryonic mesoderm) |
Protection, amniotic fluid secretion and absorption, homeostasis |
|
Yolk sac |
3rd – 8th week |
Hypoblast |
Epithelium (extraembryonic endoderm) and connective tissue (extraembryonic mesoderm) |
Gives rise to blood cells (hemopoietic), gonocytoblasts, vessels |
|
Umbilical cord |
|
Connecting stalk |
Amniotic epithelium and Wharton’s jelly (connective tissue) with two arteries, one vein, allantois and yolk sac remnants |
Connection of embryo and mother (breathing, nutrition), protection |
|
Allantois |
3rd week-2nd month |
Embryo’s endoderm |
Epithelium (cuboidal) and connective tissue |
Breathing, nutrition, blood vessels conductor, immune (B lymphocytopoiesis) |
|
Chorion |
2nd week -delivery |
Trophoblast |
Cytotrophoblast, syncytiotrophoblast, mesenchime |
Protection, connection, nutrition |
Amnion is a fetal membrane which begin its development at the third week of embryogenesis when embryoblast delamination produces epy- and hypoblast. Amniotic cavity appear in the epyblast, then extraembryonic mesoderm visceral sheet covers this structure. Thus amnion consists of epithelium of ectodermal origin and mesodermal connective tissue. Till third month this is flat epithelium, later it is transforming into cuboidal but over placenta it is tall columnar epithelium producing amniotic fluid.
Amnion has protective (amortizative) function, homeostatic function, also it produces (columnar) and absorbs (cuboidal) amniotic fluid.
The amniotic cavity is filled with a clear, watery fluid that is produced in part by amniotic cells but is derived primarily from maternal blood. The amount of fluid increases from approximately 30 ml at 10 weeks of gestation to 450 ml at 20 weeks to 800 to 1000 ml at 37 weeks. During the early months of pregnancy, the embryo is suspended by its umbilical cord in this fluid, which serves as a protective cushion. The fluid (a) absorbs jolts, (b) prevents adherence of the embryo to the amnion, and (c) allows for fetal movements. The volume of amniotic fluid is replaced every 3 hours. From the beginning of the fifth month, the fetus swallows its own amniotic fluid and it is estimated that it drinks about 400 ml a day, about half of the total amount. Fetal urine is added daily to the amniotic fluid in the fifth month, but this urine is mostly water, since the placenta is functioning as an exchange for metabolic wastes. During childbirth, the amnio-chorionic membrane forms a hydrostatic wedge that helps to dilate the cervical canal.
Hydramnios or polyhydramnios is the term used to describe an excess of amniotic fluid (1500–2000 ml), whereas oligohydramnios refers to a decreased amount (less than 400 ml). Both conditions are associated with an increase in the incidence of birth defects. Primary causes of hydramnios include idiopathic causes (35%), maternal diabetes (25%), and congenital malformations, including central nervous system disorders (e.g., anencephaly) and gastrointestinal defects (atresias, e.g., esophageal) that prevent the infant from swallowing the fluid. Oligohydramnios is a rare occurrence that may result from renal agenesis.
Premature rupture of the amnion, the most common cause of preterm labor, occurs in 10% of pregnancies. Furthermore, clubfoot and lung hypoplasia may be caused by oligohydramnios following amnion rupture. Causes of rupture are largely unknown, but in some cases trauma plays a role.
Amniotic Bands.Occasionally, tears in the amnion result in amniotic bands that may encircle part of the fetus, particularly the limbs and digits. Amputations, ring constrictions, and other abnormalities, including craniofacial deformations, may result. Origin of the bands is probably frominfection or toxic insults that involve either the fetus, fetal membranes, or both. Bands then form from the amnion, like scar tissue, constricting fetal structures.
At about the same time with amnion (3-8 week) yolk sac is developing from the hypoblast. Primary entoderm gives rise to flat epitelium and extraembryonic mesoderm visceral sheet lines it outside being transforming into connective tissue.
In human embryogenesis yolk sac had lost its first and principal function – to store the nutritive substances – but it has some more important functions, for example, it performs hemopoietic function: hemopoietic islets with blood steam cells appear at the 3rd week in the mesenchyme of yolk sac. Extraembryonic entoderm (simple squamous epithelium) is the source of primary gonocytoblasts which migrate to the gonads and there differentiate in germ cells. From the 7th-8th week of embryogenesis yolk sac undergo fast involution, its remnant could be found later in the umbilical cord.
Allantois as a fingerlike process of primary intestine ventral wall appears at about 16th day of embryonic development. It grows up from the caudal portion of intestine into the connecting stalk (amniotic foot) and may be observed there till 2 month. Allantois consists of cuboidal endodermal epithelium surrounded with connective tissue (visceral layer of extraembryonic mesoderm). It has excretory and respiratory functions, it is the guide of blood vessels in umbilical cord and, at last, it performs immune function (primary B-lymphocytes, which are involved in humoral immunity, appear in its wall).
Umbilical cord is a tube-like organ which arise of connecting stalk (amniotic foot) when the amnion is growing up. That’s why, it is covered with cuboidal epithelium of amniotic origin and it is full up with Wharton’s jelly (mucous connective tissue). It is connective tissue with a special properties, which contains much glucosaminoglycans and numerous macrophages and must cells but has no fibers. There are two arteries, one vein and the remnants of yolk sac and allantois in umbilical cord. Pay attention, please, vein supplies oxygenated blood from placenta to fetus in opposite to arteries which contain deoxygenated blood.
The remnants of yolk sac and allantois could be seen in mucous tissue. Space of yolk sac usually is irregular, space is flattened because its wall consists of squamous epithelium originating from extraembryonic endoderm. Sometime blood vessels are present in the wall of yolk sac. Space of allantois is smaller; wall is lined with cuboidal epithelium which originates from primitive intestine of embryo.
Umbilical cord connects fetus with fetal portion of placenta and performs functions of excretion, breathing and nutrition.
At birth, the umbilical cord is approximately 2 cm in diameter and 50 to 60 cm long. It is tortuous, causing false knots. An extremely long cord may encircle the neck of the fetus, usually without increased risk, whereas a short one may cause difficulties during delivery by pulling the placenta from its attachment in the uterus.
Normally there are two arteries and one vein in the umbilical cord. In 1 in 200 newborns, however, only one artery is present, and these babies have approximately a 20% chance of having cardiac and other vascular defects. The missing artery either fails to form (agenesis) or degenerates early in development.
Cross section of umbilical cord.
1. Amniotic epithelium. 2. Wharton’s jelly. 3. Vein. 4. Artery.
5. Yolk sac remnant. 6. Allantois remnant.
Chorion is developing from trophoblast when it is differentiating into cytotrophoblast and syncytiotrophoblast and underlying with extraembryonic mesoderm parietal sheath. There are two periods of chorion happening: 1) previllious –till 7-8th day and 2) period of villi formation –9-50th day.
Primary villi appear when the cells of the cytotrophoblast proliferate locally and penetrate into the syncytium, thus forming cellular columns surrounded be syncytium. During further development (12-13th day) mesodermal cells penetrate the core of primary villi and grow in the direction of uterine mucosa. The newly formed structures, the secondary stem villi, are composed of a loose connective tissue core covered by a layer of cytotrophoblastic cells, which in turn is covered by a thin layer of syncytium.
By the end of the third week the mesodermal cells in the core of the villus begin to differentiate into blood cells and small blood vessels, thus forming the villous capillary system. The villi are now known as tertiary stem villi, and during the fourth week of development this type of villi cam be found over the entire surface of the chorion.
Scheme of chorionic villi formation.
Such chorion with villi is so-called bushy chorion (chorion frondosum). But later (by the third month) branched villi may be observed only in the placental portion of chorion, the other surface will lost the villi and form chorion laeve with smooth surface.
Each villus has a core of mesenchymal connective tissue and fetal blood vessels. The mesenchymal core contains two major cell types:
1. Mesenchymal cells, which differentiate into fibroblasts, involved in the synthesis of various types of collagen (types I, III, V, and VI) and extracellular matrix components.
2. Hofbauer cells, phagocytic cells predominant in early pregnancy.
The mesenchymal core is covered by two cell types:
1. Syncytiotrophoblastic cells, in contact with the maternal blood in the intervillous space.
2. Cytotrophoblastic cells, subjacent to the syncytiotrophoblast and supported by a basal lamina.
Several important structural characteristics define the cytotrophoblast and syncytiotrophoblast:
1. Cytotrophoblastic cells divide by mitosis and differentiate into syncytiotrophoblastic cells. In contrast, the syncytiotrophoblastic cell is postmitotic.
2. Cytotrophoblastic cells are linked to each other and to overlying syncytiotrophoblast by desmosomes.
3. The apical surface of the syncytiotrophoblast contains numerous microvilli.
4. Deposits of fibrin are frequently seen on the villus surface on areas lacking syncytiotrophoblastic cells and preceding reepitheliazation.
Fetal vessels are separated from maternal blood in the intervillous space by the placental barrier.
After the fourth month of pregnancy, the fetal blood vessels become dilated and are in direct contact with the subendothelial lamina. Cytotrophoblastic cells decrease iumber and syncytiotrophoblastic cells predominate. The fetal connective tissue of the villus is nit prelevant in the mature placenta.
human Fetal period
The fetal period extends from the ninth week of gestation until birth and is characterized by rapid growth of the body and maturation of organ systems. Growth in length is particularly striking during the third, fourth, and fifth months (approximately 5 cm per month), while increase in weight is most striking during the last 2 months of gestation (approximately 700 g per month). A striking change is the relative slowdown in the growth of the head. In the third month, it is about half of CRL. By the fifth month the size of the head is about one-third of CHL, and at birth it is one-fourth of CHL. During the fifth month, fetal movements are clearly recognized by the mother, and the fetus is covered with fine, small hair.
A fetus born during the sixth or the beginning of the seventh month has difficulty surviving, mainly because the respiratory and central nervous systems have not differentiated sufficiently.
In general, the length of pregnancy for a full-term fetus is considered to be 280 days, or 40 weeks after onset of the last menstruation or, more accurately, 266 days or 38 weeks after fertilization.
The amnion is a large sac containing amniotic fluid in which the fetus is suspended by its umbilical cord. The fluid (a) absorbs solts, (b) allows for fetal movements, and (c) prevents adherence of the embryo to surrounding The fetus swallows amniotic fluid, which is absorbed through its gut and cleared by the placenta. The fetus adds urine to the amniotic fluid, but this is mostly water. An excessive amount of amniotic fluid (hydramnios) is associated with anencephaly and esophageal atresia, whereas an insufficient amount (oligohydramnios) is related to renal agenesis.
The umbilical cord, surrounded by the amnion, contains (a) two umbilical arteries, (b) one umbilical vein, and (c) Wharton’s jelly, which serves as a protective cushion for the vessels.
Fetal membranes in twins vary according to their origin and time of formation. Two-thirds of twins are dizygotic, or fraternal; they have two amnions, two chorions, and two placentas, which sometimes are fused. Monozygotic twins usually have two amnions, one chorion, and one placenta. In cases of conjoined twins, in which the fetuses are not entirely split from each other, there is one amnion, one chorion, and one placenta.
Signals initiating parturition (birth) are not clear, but preparation for labor usually begins between 34 and 38 weeks. Labor itself consists of three stages: 1) effacement and dilatation of the cervix; 2) delivery of the fetus; and 3) delivery of the placenta and fetal membranes.
Uterine decidual tunics
By the 11th to 12th day of development the blastocyst is completely embedded in the endometrial stroma, and the uterine surface epithelium covers almost entirely the original defect in the epithelial lining of the mucosa. In the latter, embryo is developed inside in the endometrium which produce decidual tunics. The decidua over the chorion frondosum, the decidua basalis (maternal placenta), consists of a compact endometrial layer of large cells with abundant amounts of lipids and glycogen (decidual cells). This layer is tightly connected to the chorion. The decidual layer over the abembryonic pole is known as decidua capsularis. At first it is similar to decidua basalis but with increase in the size of the chorionic vesicle, this layer becomes stretched, and begins to degenerate. Subsequently, the chorion laeve comes into contact with the epithelium of the decidua parietalis on the opposite side of the uterus and the two fuse. The lumen of the uterus is then obliterated. Hence, the only functional portion of the chorion is the chorion frondosum and together with the decidua basalis, the two make up the placenta.
Types of placentas due to their structure
A. Epitheliochorial
B. Desmochorial
C. Endotheliochorial
D. Hemochorial placenta
Types of placentas due to the type of embryo nutrition
A. First type (diffuse and numerous placentas).
B. Second type placentas are producing the proteins, which are typical to embryo (tape and discoid).
Human placenta is of nutrition secondary type, discoid and hemochorial.
The placenta consists of two components: (a) a fetal portion, derived from the chorion frondosum or villous chorion, and (b) a maternal portion, derived from the decidua basalis. The space between the chorionic and decidual plates is filled with intervillous lakes of maternal blood. Villous trees (fetal tissue) grow into the maternal blood lakes and are bathed in them. The fetal circulation is at all times separated from the maternal circulation by (a) a syncytial membrane (a chorion derivative) and (b) endothelial cells from fetal capillaries. Hence the human placenta is of the hemochorial type. Intervillous lakes of the fully grown placenta contain approximately 150 ml of maternal blood, which is renewed 3 or 4 times per minute. The villous area varies from 4 to 14 m2, facilitating exchange between mother and child.
Main functions of the placenta are (a) exchange of gases; (b) exchange of nutrients and electrolytes; (c) transmission of maternal antibodies, providing the fetus with passive immunity; (d) production of hormones, such as progesterone, estradiol, and estrogen (in addition, it produces hCG and somatomammotropin); and (e) detoxification of some drugs.
Maternal placenta structure
Thus, placenta is a unic organ which consists of two principally different structures of both – mammy and baby.
There may be recognized a few type of placenta due to their type of nutrition and structure. In opposite to placentas of first type the second type placenta are producing the proteins which are typical to embryo. There are diffuse and numerous placentas in the first group and tape and diskoidal in the second one.
Chorionic villi may contact with different maternal tissue of endometrium that’s why there are 4 types of placentas due to their structure: 1) epitheliochorial, 2) desmochorial, 3) endotheliochorial and 4) hemochorial placenta.
Human placenta is of secondary type of nutrition and hemochorial.
1 – umbilical arteries, 2 – stem villus, 3 – decidual septa, 4 – decidual layer, 5 –myometrium, 6 – veins, 7 – spiral arteries, 8 – chorion, 9 – amnion, 10 – intervillous space, 11 – umbilical vein, 12 – cotyledon.
Human placenta and umbilical cord surface view at the end of pregnancy.
1 – umbilical cord, 2 – fetal placenta, 3 – maternal placenta, 4 – cotyledone, 5 – amnion, 6 – blood vessels.
By the beginning of the fourth month, the placenta has two components: 1) a fetal portion formed by the chorion frondosum and, 2) a maternal portion formed by the decidua basalis. On the fetal side the placenta is bordered by the chorionic plate; on its maternal side by the decidua basalis, of which the compact layer or decidual plate is most intimately incorporated into the placenta. In the so-called junctional zone the trophoblast and decidua cells intermingle.this zone, which represents the zone of invasion of the trophoblastic cells into the uterine tissues, is characterized by decidual and syncytial giant cells and rich in amorphous mucopolysaccharide material. Between the chorionic and decidual plates are the intervillous spaces which are filled with maternal blood. They are derived from the lacunae in the syncytiotrophoblast and are at all times lined with syncytium of a fetal origin. The villous trees grow into the intervillous blood lakes.
During pregnancy the endometrial connective cells transform into decidual cells. The endometrium is then called decidua, and 3 regions of mucosa can be recognized: decidua basalis, capsularis, and parietalis.
During the fourth and fifth months the decidua forms a number of septa, the decidual septa, which project into the intervillous spaces but do not reach the chorionic plate. As the result of this septum formation, the placenta is dividedinto a number of compartments or cotyledons. Since the decidual septa do not reach the chorionic plate, contact between the intervillous space in the various cotyledons is maintained.
In the second half of pregnancy lacuna surface is covered by special membrane – Ror fibrinod which appears from syncytiotrophoblast. Similar fibrinoid of Langhans covers chorionic villi in the third trimester of pregnancy.
At full term, the placenta has discoid shape, a diameter of 15 to
Cotyledone is the structural unit of placenta, it is adequate to steam chorionic villus with surrounding endomethrium.
The fetal portion of placenta does not show a cotyledon structure, and is covered entirely by the chorionic plate. A number of large arteries and veins, the chorionic vessels, are seen to converge toward the umbilical cord. The chorion in turn is covered by the amnion. The attachment of the umbilical cord is usually eccentric and occasionally even marginal. Rarely, however, does it insert into the chorionic membrane outside the placenta (velamentous insertion).
So, the mature placenta is 3 cm thick, has a diameter of 20 cm, and weights about 500 g. The fetal side is smooth and associated with the amniotic membrane. The maternal side is partially subdivided into 10 or more lobes by decidual septa derived from the deciduas basalis and extending toward the chorionic plate. The decidual septa do not fuse with chorionic plate.
The fetal surface of the placenta is covered entirely by the chorionic plate. A number of large arteries and veins, the chorionic vessels, converge toward the umbilical cord .The chorion is covered by the amnion. Attachment of the umbilical cord is usually eccentric and occasionally even marginal. Rarely, however, does it insert into the chorionic membranes outside the placenta (velamentous insertion).
CIRCULATION OF THE PLACENTA
Cotyledons receive their blood through 80 to 100 spiral arteries that pierce the decidual plate and enter the intervillous spaces at more or less regular intervals. The lumen of the spiral artery is narrow, so blood pressure in the intervillous space is high. This pressure forces the blood deep into the intervillous spaces and bathes the numerous small villi of the villous tree in oxygenated blood. As the pressure decreases, blood flows back from the chorionic plate toward the decidua, where it enters the endometrial veins (Fig. 6.13). Hence, blood from the intervillous lakes drains back into the maternal circulation through the endometrial veins.
Collectively, the intervillous spaces of a mature placenta contain approximately 150 ml of blood, which is replenished about 3 or 4 times per minute. This blood moves along the chorionic villi, which have a surface area of 4 to 14 m2. However, placental exchange does not take place in all villi, only in those whose fetal vessels are in intimate contact with the covering syncytial membrane. In these villi, the syncytium often has a brush border consisting of numerous microvilli, which greatly increases the surface area and consequently the exchange rate between maternal and fetal circulations. The placental membrane, which separates maternal and fetal blood, is initially composed of four layers: (a) the endothelial lining of fetal vessels; (b) the connective tissue in the villus core; (c) the cytotrophoblastic layer; and (d) the syncytium. From the fourth month on, however, the placental membrane thins, since the endothelial lining of the vessels comes in intimate contact with the syncytial membrane, greatly increasing the rate of exchange.
Sometimes called the placental barrier, the placental membrane is not a true barrier, since many substances pass through it freely. Because the maternal blood in the intervillous spaces is separated from the fetal blood by a chorionic derivative, the human placenta is considered to be of the hemochorial type.
Placental blood circulation has two relevant characteristics: 1 – the fetal blood circulation is closed (within blood vessels), 2 – the maternal blood circulation is open (not bound by blood vessels). Maternal blood enters the intervillous space under reduced pressure, regulated by the cytotrophoblastic cell plugs, and leaves through the uterine veins after exchanges occur with the fetal blood in the terminal branched villi.
The umbilical vein has a subendothelial elastic lamina; the two umbilical arteries lack an elastic lamina. The umbilical vein carries 80% oxygenated fetal blood. Although the partial pressure of oxygen in fetal blood is low (20 to 25 mm Hg), the higher cardiac output in organ blood flow, higher Hb concentration (by the way HbF) in fetal red blood cells, and higher oxygen saturation provide adequate oxygenation to the fetus.
The umbilical arteries return deoxygenated fetal blood to the placenta.
Main functions of the placenta are the next:
1) nutritive (exchange of nutrients and electrolytes, such as amino acids, free fatty acids, carbohydrates, and vitamins, is rapid and increases as pregnancy advances);
2) excretory;
3) protective;
4) immune (transmission of maternal antibodies. Immunological competence begins to develop late in the first trimester, by which time the fetus makes all of the components of complement. Immunoglobulins consist almost entirely of maternal immunoglobulin G (IgG) that begins to be transported from mother to fetus at approximately 14 weeks.
In this manner, the fetus gains passive immunity against various infectious diseases. Newborns begin to produce their own IgG, but adult levels are not attained until the age of 3 years;
5) respiratory (exchange of gases, such as oxygen, carbon dioxide, and carbon monoxide, is accomplished by simple diffusion. At term, the fetus extracts 20 to 30 ml of oxygen per minute from the maternal circulation and even a short-term interruption of the oxygen supply is fatal to the fetus. Placental blood flow is critical to oxygen supply, since the amount of oxygen reaching the fetus primarily depends on delivery, not diffusion).
6) endocrine (for example endocrine function of placenta includes synthesis of hormones likes progesterone, estrogens, insulin like hormone etc).
Structural components of haemochorial barrier
Hemochorial (placental) barrier is a dividing membrane between the maternal and fetal circulations. In the early stages it consists of four layers: 1) the endothelial lining of the fetal vessels, 2) the connective tissue in the core of villus, reach in macrophages, 3) the cytotrophoblastic layer, and 4) the covering syncytium.
From the fourth month on, however, the placental barrier becomes much thinner, since most of the villi lose their cytotrophoblastic layer as well as the connective tissue surrounding the fetal capillaries. The endothelial lining of the vessels comes then in intimate contact with the syncytial membrane, thus greatly increasing the rate of exchange. In the final stages of pregnancy, the small villi show an extremely thin, double-layered membrane separating the maternal and fetal circulations. These layers, however, persist at all times. It is necessary to underline that placental barrier is very strong and safely protect an embryo from different negative influence. For example, AID virus can pass through this barrier only in 25 % cases. It is unpenetratable to bacteria.
Most maternal hormones do not cross the placenta. The hormones that do cross, such as thyroxine, do so only at a slow rate. Some synthetic progestins rapidly cross the placenta and may masculinize female fetuses. Even more dangerous was the use of the synthetic estrogen diethylstilbestrol, which easily crosses the placenta. This compound produced carcinoma of the vagina and abnormalities of the testes in individuals who were exposed to it during their intrauterine life.
Although the placental barrier is frequently considered to act as a protective mechanism against damaging factors, many viruses, such as rubella, cytomegalovirus, Coxsackie, variola, varicella, measles, and poliomyelitis virus, traverse the placenta without difficulty. Once in the fetus, some viruses cause infections, which may result in cell death and birth defects.
Unfortunately, most drugs and drug metabolites traverse the placenta without difficulty, and many cause serious damage to the embryo.
In addition, maternal use of heroin and cocaine can cause habituation in the fetus.
Critical (crucial) periods of human ontogenesis
In the human ontogenesis there are some periods of especially high sensibility to different influences. At first Australian scientist Norman Gregg had told about this periods in 1944. Later, in 1960, Russian morphologist P. Svetlov had grounded a theory of critical periods of embryogenesis. He thought, that in the course of ontogenesis there are some periods of an important quantitive changes. Some negative influences from outside may damage human organism at that moment and even interrupt the pregnancy or cause the death.
Such important events are:
1. Progenesis or gametogenesis which is characterized by specific changes of chromosomes amount in mejosis.
2. Fertilization – merging the gametes and restorations of the chromosomes amount.
3. Implantation – introducing of the embryo into the endometrium (7-8 day).
4. Placentation (3-8th week).
5. Growth of the brain (15-20th week).
6. Organo- and systemogenesis (formation of the vitally important system 20-24th week).
7. The birth.
8. Neonatal period and first year of life.
9. Pubertation (11-16th years).
10. Menopause.
During last period of time in medical practice of many countries of the world so-called “artifitial fertilization” (correct term “extracorporal fertilization”) is used very often in the case of male or female infertility.
It was in
What is extracorporal fertilization.
1. Special surgical manipulation allows to take few oocytes before ovulation.
2. Fertilization occurs “in vitro” in special lab tube.
3. Incubation lasts for 3-4 days (period of cleavage)
4. Blastocysts which consist of 18-32 blastomeres – “free blastocyst” is introduced in uterus. Usually more then one blasocyst begin to implant, so pregnancy is multiple.
5. 15 % of implantation are successful.
There are some advances of such extracorporal fertilization:
1. It is possible to choice the future sex of baby (this allow to shun some hereditary diseases).
2. The sperm may be reached with spermatozoa, abnormal ones may be picked out.
3. Abnormal sites of implantation are almost impossible in such case, i.e. tubal or abdominal pregnancy.
Real-life situations to be solved
1. A lot of spermatozoa with spherical head were revealed in histological research of spermatozoa smear. What may it cause?
2. After spermatozoon head introduction into oocyte content of cortical granules of oocyte is released outside. What is the name of this process?
3. At distant stage of fertilization spermatozoa move against fluid flow toward oocyte. What is the name of this addressed movement?
4. At some stage of embryogenesis human embryo looks like vesicle with space. Its wall consists of light small blastomeres and larger dark ones at one pole. What is the name of embryo at this stage?
5. Cleavage of zygote result in blastula formation. Which type of blastula is typical for human embryogenesis?
6. Due to expression of cell genome components embryonic cells obtain characteristic morphological, biochemical and fuctional peculiarities. Name this process.
7. Histological specimens are stained with hematoxylin and eosin. They have different oocytes. Which one is human oocyte?
8. In endoscopy of uterine space embryo was revealed. It was not attached to endometrium. What is this stage of embryogenesis?
9. In experiment in vivo it is fixed a moment in which spermatozoa surround oocyte and corona radiate disappears. What is the name of this process?
10. In first crucial period of embryogenesis (5th -6th day) tunic of fertilization suddenly disappear. Embryo at this time was placed in uterine tube. What may it result in?
11. In histological research of spermatozoa smear dense structures are revealed at the top of heads. What are these structures?
12. In histological specimen it is seen oocyte at moment of fertilization by spermatozoon. What is main result of this process?
13. In histological specimen it is seen oocyte at moment of fertilization by spermatozoon. What is usual place of fertilization?
14. Inner sex organs of woman were excised in surgical operation. Embryo which consists of two cells was found in histological research of these organs. What is usual localization of such embryo iormal condition?
15. Inner sex organs of woman were excised in surgical operation. Embryo which consists of 16 tightly packed blastomeres was found in histological research of these organs. What is the name of this embryo?
16. Inner sex organs of woman were excised in surgical operation. Embryo which consists of 16 tightly packed blastomeres was found in histological research of these organs. It is cowered with special tunica. What is the name of this tunica?
17. Multiple penetrations of spermatozoa into one oocyte are impossible. Why? What is it due to?
18. Process of embryo implantation into uterine mucosa consists of two stages. What is morphological evidence of first stage?
19. Process of spermatozoon head penetration into oocyte is seen in histologic specimen. What is the name of this process?
20. When spermatozoa are placed in vagina after ovulation they begin to move faster. What is the name of this process (special activation of spermatozoa)?
21. A lot of spermatozoa with spherical head were revealed in histological research of spermatozoa smear. What may it cause?
22. After spermatozoon head introduction into oocyte content of cortical granules of oocyte is released outside. What is the name of this process?
23. At distant stage of fertilization spermatozoa move against fluid flow toward oocyte. What is the name of this addressed movement?
24. At some stage of embryogenesis human embryo looks like vesicle with space. Its wall consists of light small blastomeres and larger dark ones at one pole. What is the name of embryo at this stage?
25. Cleavage of zygote result in blastula formation. Which type of blastula is typical for human embryogenesis?
26. Due to expression of cell genome components embryonic cells obtain characteristic morphological, biochemical and fuctional peculiarities. Name this process.
27. Histological specimens are stained with hematoxylin and eosin. They have different oocytes. Which one is human oocyte?
28. In endoscopy of uterine space embryo was revealed. It was not attached to endometrium. What is this stage of embryogenesis?
29. In experiment in vivo it is fixed a moment in which spermatozoa surround oocyte and corona radiate disappears. What is the name of this process?
30. In first crucial period of embryogenesis (5th -6th day) tunic of fertilization suddenly disappear. Embryo at this time was placed in uterine tube. What may it result in?
31. In histological research of spermatozoa smear dense structures are revealed at the top of heads. What are these structures?
32. In histological specimen it is seen oocyte at moment of fertilization by spermatozoon. What is main result of this process?
33. In histological specimen it is seen oocyte at moment of fertilization by spermatozoon. What is usual place of fertilization?
34. Inner sex organs of woman were excised in surgical operation. Embryo which consists of two cells was found in histological research of these organs. What is usual localization of such embryo iormal condition?
35. Inner sex organs of woman were excised in surgical operation. Embryo which consists of 16 tightly packed blastomeres was found in histological research of these organs. What is the name of this embryo?
36. Inner sex organs of woman were excised in surgical operation. Embryo which consists of 16 tightly packed blastomeres was found in histological research of these organs. It is cowered with special tunica. What is the name of this tunica?
37. Multiple penetrations of spermatozoa into one oocyte are impossible. Why? What is it due to?
38. Process of embryo implantation into uterine mucosa consists of two stages. What is morphological evidence of first stage?
39. Process of spermatozoon head penetration into oocyte is seen in histologic specimen. What is the name of this process?
40. When spermatozoa are placed in vagina after ovulation they begin to move faster. What is the name of this process (special activation of spermatozoa)?
41. A lot of spermatozoa with spherical head were revealed in histological research of spermatozoa smear. What may it cause?
42. After spermatozoon head introduction into oocyte content of cortical granules of oocyte is released outside. What is the name of this process?
43. At distant stage of fertilization spermatozoa move against fluid flow toward oocyte. What is the name of this addressed movement?
44. At some stage of embryogenesis human embryo looks like vesicle with space. Its wall consists of light small blastomeres and larger dark ones at one pole. What is the name of embryo at this stage?
45. Cleavage of zygote result in blastula formation. Which type of blastula is typical for human embryogenesis?
46. Due to expression of cell genome components embryonic cells obtain characteristic morphological, biochemical and fuctional peculiarities. Name this process.
47. Histological specimens are stained with hematoxylin and eosin. They have different oocytes. Which one is human oocyte?
48. In endoscopy of uterine space embryo was revealed. It was not attached to endometrium. What is this stage of embryogenesis?
49. In experiment in vivo it is fixed a moment in which spermatozoa surround oocyte and corona radiate disappears. What is the name of this process?
50. In first crucial period of embryogenesis (5th -6th day) tunic of fertilization suddenly disappear. Embryo at this time was placed in uterine tube. What may it result in?
51. In histological research of spermatozoa smear dense structures are revealed at the top of heads. What are these structures?
52. In histological specimen it is seen oocyte at moment of fertilization by spermatozoon. What is main result of this process?
53. In histological specimen it is seen oocyte at moment of fertilization by spermatozoon. What is usual place of fertilization?
54. Inner sex organs of woman were excised in surgical operation. Embryo which consists of two cells was found in histological research of these organs. What is usual localization of such embryo iormal condition?
55. Inner sex organs of woman were excised in surgical operation. Embryo which consists of 16 tightly packed blastomeres was found in histological research of these organs. What is the name of this embryo?
56. Inner sex organs of woman were excised in surgical operation. Embryo which consists of 16 tightly packed blastomeres was found in histological research of these organs. It is cowered with special tunica. What is the name of this tunica?
57. Multiple penetrations of spermatozoa into one oocyte are impossible. Why? What is it due to?
58. Process of embryo implantation into uterine mucosa consists of two stages. What is morphological evidence of first stage?
59. Process of spermatozoon head penetration into oocyte is seen in histologic specimen. What is the name of this process?
60. When spermatozoa are placed in vagina after ovulation they begin to move faster. What is the name of this process (special activation of spermatozoa)?
Student’s Practical Activities
Task No 1. Students must know and illustrate such a histologic specimens.
Specimen 1. Embryo at the primitive streak stage.
Stained with iron hematoxylin.
At the low magnification you can see the primitive streak consisting of dense cord of cells. Laterally to the primitive streak there are three germ layers, which lie separately: primary ectoderm, endoderm and mesoderm, which appear due to the primitive streak cells migration.
Illustrate and indicate: 1. Primitive streak. 2. Epiblast. 3. Hypoblast. 4. Mesoderm.
Specimen 2. Embryo at the stage of axial organs development.
Stained with iron hematoxylin.
Place specimen with nervous tube up. At a law magnification you can recognise multilayered ectoderm coveres the embryo and nervous tube under it. There are mesoderm somits at the sides, notochord under the nervous tube and the lowest part – endoderm. Somits and splanchnotom are connected by intermediate mesoderm. There are two layers of a splanchnotom: splanchnic and somatic ones. Embryonic connective tissue which lies between germ layers is termed mesenchime.
Illustrate and indicate: 1. Ectoderm. 2. Neural tube. 3. Notochord. 4. Somit. 5. Splanchnic mesoderm layer. 6. Somatic mesoderm layer. 7 Endoderm. 8. Coelomic cavity. 9. Mesenchime. 10. Intermediate mesoderm (segmented feet or nephrogonotome)
Specimen 3. 14-days human embryo. Scheme.
Illustrate and indicate: 1. Syncytiotrophoblast. 2. Cytotrophoblast. 3. Chorionic mesoderm. 4. Amniotic cavity. 5. Amniotic ectodermal epithelium. 6. Amniotic mesoderm. 7. Epiblast with primitive streak. 8. Hypoblast. 9. Yolk sac cavity. 10. Yolk sac endodermal epithelium. 11. Yolk sac mesoderm. 12. Blastocele.
Specimen 4. Umbilical cord.
Stained with H & E.
In the specimen you see the cross section of umbilical cord, which is cowered with amniotic epythelium. Extraembrionic connective tissue presents the slroma of umbilical cord (jelly of Wharton). There are 2 arteries and one vein there. Arteries pass the blood from the embryo and vein – to him. Very often there is a remnant of yolk sac too. It looks like a weak split cowered with flat epithelium inside. Sometimes blood islets are seen in the yolk sac wall. The remnant of allantois has a small cavity separated by cuboidal epithelium.
Illustrate and indicate: 1. Amniotic epithelial cells. 2. Connective tissue. 3. Vein. 4. Artery. 5. Yolk sac remnant. 6. Allantois remnant.
Specimen 5. Amnion.
Stained with H & E.
At a high magnification it is seen the polygonal shape cells border. There are dense contacts between them. (They are densely contact with each other).
Illustrate and indicate: 1. Amniotic epitheliocytes
Specimen 6. Branched chorion villi.
Stained with PASS-reaction.
Find the branched chorion villus at a low magnification in microscope. Pay attention that large villus is branching into small ones. Dark red (brownish) coloured cells of trophoblast present their borders.
Illustrate and indicate: 1. Branched chorionic villus.
Specimen 7. Fetal placenta.
Stained with H & E
The fetal portion of placenta is covered with amniotic tunice, with a simple prismatic epithelium. There is a chorionic plate under the amnion which contains large vessels. These structures are covered with cyto- and symplastotrophoblast outside. They are disposed in lacunes with maternal blood. On the cross section of villi it is seen: the wall of chorionic villi fulfilled with connective tissue. Sometimes fetal vessels are seen there.
Illustrate and indicate: 1. Amniotic tunice. 2, C%orionic plate with umbilical vessels,
3. Chorionic villi: a) cytotrophoblast shell; b) symplastotrophoblast; c) villus stroma; d) vessels.
Specimen 8. Maternal placenta.
Stained with H & E.
Maternal placenta consists of basal lamina (decidua mucouse uterine tunice) with numerous decidual cells and connective tissue septae. Decidual cells are large oval shaped cells with cytoplasm of light pink color. These septae separate villi in lacunae with maternal blood.
Illustrate and indicate: 1. Decidual plate. 2. Decidual cells. 3. Decidual septum.
4. Lacunar spaces with maternal blood. 5. Villi.
References
1. Medical Embryology. Langman J. Baltimore. Wilkins Co. 1969. P. 37-78.
2. L. Carlos Junqueira, Jose Carneiro, Robert O. Kelley. Basic Histology. – 7th ed. Appleton and Lange.
3. Inderbir Singh. Textbook of Human Histology with colour atlas. – 4th ed. Jaypee Brothers Medical Publishers (P) LTD, 2002, pp.
4. Study Guide and review Manual of Human Embryology. Keight L. Moore. W. B. Saunders Company,
5. Tissues and organs: a text atlas of scanning electron microscopy. – Kessel RG, Kardon RH. – Freeman Co. – 1979.
6. Ham, A. W.: Histology, eg.7.
7. Victor P. Eroschenko. Atlas of Histology with functional correlations. – 9th ed. Lippincott Williams and Wilkins, 2000. – pp. 267-277, 281.
8. Webster’s Medical Desk Dictionary. –
9. Charts:
http://intranet.tdmu.edu.ua/index.php?dir_name=kafedra&file_name=tl_34.php#n15
10. Disk:
http://intranet.tdmu.edu.ua/index.php?dir_name=cd&file_name=index.php#3
11. Волков К.С. – Ультраструктура клiтин i тканин. Навчальний посiбник-атлас. 1997 р., 95 с.
http://intranet.tdmu.edu.ua/data/books/Volkov(atlas).pdf
12. О.Д.Луцик і співавт. – Гiстологiя людини. – Київ: Книга плюс, 2003 р. –592
http://intranet.tdmu.edu.ua/data/books/gistologia_lucyk.pdf
http://en.wikipedia.org/wiki/Histology
http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html
http://www.kumc.edu/instruction/medicine/anatomy/histoweb/
http://www.udel.edu/biology/Wags/histopage/histopage.htm
