Special Histology and Embryology: Practical Course - V. K. Naphanyuk 2001

Early stages of human embryo development
Embryonic period

Studying the fundamentals of human Embryology and understanding the physiological dynamics of its developmental features across various Stages of the embryonic period enables physicians to comprehend and, whenever possible, correct developmental pathologies, or in some cases even prevent them. Insight into the relationship between the fetus and the maternal Organism makes it possible to evaluate the full cycle of biological phenomena accompanying Pregnancy, which is crucial for determining delivery management tactics and prognosticating fetal health.

Prenatal Human Development is divided into the embryonic period (the first 8 weeks) and the fetal period.

The embryonic period (periodus embryonica) is characterized by the initiation of development for all embryonic and extraembryonic structures. The three germ layers formed during this time differentiate into various Tissues and Organs. By the end of the embryonic period, all major Organ Systems not only begin to develop, but many of them also exhibit specific functional activity. In human development, this period is critical; it is particularly susceptible to the Influence of the maternal organism and A wide variety of environmental factors. The embryonic period begins with Fertilization.

Fertilization (fertilisatio) is The process of fusion between male and Female Germ Cells, resulting in The formation of a single-celled embryo — the zygote.

Human fertilization is monospermic and, in terms of its dynamics, does not differ from fertilization in other mammals.

Following ovulation, the oocyte (secondary oocyte) reaches the fimbriae of the Uterine tube and moves into its ampullary region. The oocyte is surrounded by the corona radiata and is in metaphase of the second maturation division (Fig. 80).

Upon entering the female reproductive tract, the spermatozoon undergoes capacitation (Fig. 81), which lasts about 7 hours: the glycoprotein coat and seminal Plasma Proteins disappear from Cell/30.html">The Plasma Membrane in the region of the sperm acrosome, triggering the acrosome reaction. Following capacitation, as the spermatozoon migrates toward the corona radiata, the acrosome reaction takes place. The outer acrosomal membrane "fuses" in numerous areas with the anterior 2/3 of the sperm HEAD's cytoplasmic membrane. Following fusion, the membranes rupture, forming small vesicles and numerous pores through which the Proteolytic Enzymes of the acrosome are released. The enzyme hyaluronidase initiates the "dispersion" of the corona radiata cells, while a Trypsin-like substance helps the spermatozoon penetrate the zona pellucida. The zona pellucida retains spermatozoa, which is associated with the presence of glycoprotein sperm receptors on its surface (the number of receptors is exceptionally high). These Glycoproteins induce the acrosome reaction. The zona pellucida comes into contact with the acrosomal enzymes, which are separated from the rest of the sperm by the inner portion of the acrosomal membrane.

The enzymes break down the zona pellucida, and one of the many spermatozoa enters the perivitelline space — the region between the zona pellucida and the oocyte membrane.

Fusion occurs between the oocyte membrane and the portion of the sperm head membrane preserved after the acrosome reaction (Fig. 81). The head and tail of the spermatozoon penetrate the Cytoplasm of the human oocyte, while its plasma membrane remains outside the oocyte surface. Within a few seconds, The properties of the oocyte membrane change, rendering it impermeable to other spermatozoa (preventing polyspermy). A cortical reaction occurs within the oocyte — the release of enzymes from cortical granules, which destroys the sperm-binding capability, i.e., receptor activity.

The penetrating spermatozoon activates CELLULAR AND MOLECULAR processes in the egg, which immediately completes the second meiotic division, producing the second polar body (The Nucleus of such an egg is referred to as the female pronucleus). The spermatozoon, which is now moving toward the female pronucleus, undergoes tail degeneration. Its nucleus is initially darker than the female one, but subsequently becomes lighter due to Hydration, and these differences are reduced (the sperm nucleus is referred to as the male pronucleus). Fertilization concludes with The breakdown of the nuclear membranes of the pronuclei, their fusion, and the combination of Chromosomes.

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Fig. 80. Oocyte prior to fertilization:

a — oocyte from a follicle; b — oocyte with the first polar body

Fig. 81. Human fertilization:

A — fertilization diagram (I, II); B — egg in the uterine tube; C, D — stages of pronuclear approach (after Petrov); E — pronuclear stage 16–18 hours after fertilization (phase contrast, preparation);

1 — lumen of the uterine tube; 2 — wall of the uterine tube; 3 — egg (secondary oocyte); 4 — zona pellucida; 5 — corona radiata; 6 — lamellar structures; 7 — microvilli; 8 — spermatozoon undergoing capacitation (a); acrosome reaction and enzyme release (b); penetrating the egg membrane while leaving behind the plasma membrane (c); entering the egg cytoplasm (d); 9 — female pronucleus; 10 — male pronucleus; 11 — meiotic spindle; 12 — mitotic spindle; 13 — pronuclear chromosomes; 14 — polar bodies; 15 — degenerating sperm tail; d — Formation of the male pronucleus, degeneration of the spermatozoon tail; e — fusion of pronuclei; f — zygote, mitotic spindle of the 1st division

As a result of fertilization, the diploid set of chromosomes is restored, and new variations in their Structure are ensured. The outcome of fertilization is the initiation of zygote Cleavage. Without fertilization, the oocyte degenerates on the 2nd day following ovulation.

Cleavage (fissio) is the successive mitotic division of the zygote into cells (blastomeres) without their subsequent growth to the size of the parent cell.

The pattern of human cleavage is generally similar to that of other mammals. Cleavage of the human zygote is total (holoblastic), subequal, and asynchronous. From the first divisions, Two Types of blastomeres are formed: some are larger and darker, while others are smaller and lighter. Zygote cleavage occurs toward the end of the 1st day after fertilization (Fig. 82).

The dark blastomeres form the embryoblast (embryoblastus), while the light ones form the trophoblast (trophoblastus), which envelops the embryoblast. This Embryonic Stage is called a stereoblastula or morula (Lat. morula — little mulberry) (Fig. 83). The term "morula" is used for an embryo that lacks a cavity. Subsequently, the stereoblastula transforms into a blastocyst — an embryo in the form of a fluid-filled vesicle. The blastocyst consists of the trophoblast surrounding the blastocyst cavity, where the embryoblast is attached to the trophoblast on one side in the form of the inner cell mass (embryonic knot) (Fig. 84).

Following this (already in the Uterus), Gastrulation begins. The first phase of gastrulation occurs via delamination from the 7th to the 15th day (Fig. 85). The second phase of gastrulation is based on The Mechanism of immigration and takes place on days 15–17.

Fig. 82. Cleavage of the human zygote. Two-blastomere stage

Fig. 83. Human cellular steroblastula on the 4th day of embryonic development:

1 — trophoblast cells; 2 — embryoblast cells; 3 — polar body; 4 — remnants of the zona pellucida

Gastrulation results in the formation of germ layers and, simultaneously, extraembryonic organs, which are temporary and function exclusively during the embryonic development period.

At this stage, implantation (Latin *implantatio* — ingrowth, embedding) of the embryo into the uterine mucosa takes place. Implantation begins on the 7th day after fertilization and lasts about 40 hours. Two stages of implantation are distinguished: adhesion (attachment) and invasion (penetration).

During the first stage, the trophoblast attaches to the uterine mucosa, and two layers begin to differentiate within it — the cytotrophoblast and the symplastotrophoblast (plasmodiotrophoblast).

During the Second Stage, the symplastotrophoblast, which produces proteolytic enzymes, destroys the uterine mucosa. Concurrently, the developing trophoblast villi penetrate the uterus, successively destroying its epithelium, followed by the underlying Connective Tissue and Blood vessel walls. The trophoblast comes into direct contact with maternal blood. An implantation crypt is formed, around which areas of Hemorrhage appear in the embryo's vicinity. Initially (the first 2 weeks), the trophoblast consumes the breakdown products of maternal tissues (histiotrophic type of Nutrition); subsequently, the embryo is nourished directly from the maternal blood (hematotrophic type of nutrition).

Fig. 84. Human cellular blastula on the 4th–5th day of embryonic development:

1 — trophoblast; 2 — embryoblast; 3 — blastocoel cavity

Fig. 85. First phase of gastrulation (7.5 days):

1 — epiblast (ectoderm); 2 — hypoblast (endoderm); 3 — blastocyst cavity; 4 — trophoblast; 5 — primary villi

During embryonic development, modifications occur simultaneously both within the embryo proper and in the extraembryonic organs, which in the Cytology/cytology/16.html">Early stages of human Embryogenesis develop faster than the embryo itself, providing the necessary conditions for its development. Extraembryonic organs include the amnion, chorion, yolk sac, allantois, serosa, and Placenta.

Embryoblast cells split into two layers: the outer epiblast (including the material of the ectoderm, neural plate, mesoderm, and notochord), adjacent to the trophoblast; and the inner hypoblast (including the material of the embryonic and extraembryonic ectoderm), facing the blastocyst cavity.

Simultaneously, as fluid accumulates in the center of The Cell mass within the embryonic node, a cavity is formed. The cells surrounding it acquire an epithelial-like shape. Thus, the amniotic vesicle (*amnion primitivum*) arises, the floor of which forms the ectoderm of the embryo proper. The second part of the amniotic vesicle wall consists of extraembryonic ectoderm. Proliferating hypoblast cells form the yolk sac (*saccus vitelinus*), the roof of which faces the floor of the amniotic vesicle; this constitutes the embryonic endoderm. The adjacent floor of the amniotic vesicle and roof of the yolk sac form the embryonic disc — the material from which the body of the embryo subsequently forms.

On the 7th day, cells that have migrated from the embryonic disc are detected; they locate within the blastocyst cavity and form the extraembryonic mesoderm (mesenchyme). By the 11th day, it fills the blastocyst cavity. The mesenchyme grows toward and invades the trophoblast, thereby forming the chorion — the villous membrane of the embryo bearing primary chorionic villi. The extraembryonic mesoderm participates in the formation of the primordia of the amniotic vesicle (together with the ectoderm) and the yolk sac (together with the endoderm). A dense mesodermal cord, the so-called body stalk (connecting stalk), links the amniotic vesicle to the trophoblast (Fig. 86).

The second phase of gastrulation takes place on days 15–17. As a result of the immigration of cellular material from the embryonic disc, the primitive streak, primitive (Hensen's) node, and notochordal process are formed (Fig. 87).

The formation of the streak and primitive (Hensen's) node occurs through the displacement of ectodermal Cells of the embryonic disc into the pit at its caudal end. Ectodermal cells located rostral to the primitive node shift into the space between the ectodermal layers, forming mesodermal wings. The embryo becomes trilaminar, consisting of ectoderm, endoderm, and mesoderm, bearing a resemblance to avian embryos.

During the second phase of gastrulation, axial organs emerge: the notochord, neural tube, and dorsal mesoderm (somites). The axial organs develop from cells of the embryonic disc through their proliferation and migration, similarly to bird embryos.

On the 18th day, the neural plate becomes outlined within the ectoderm, which subsequently transforms into the neural groove and then into the neural tube — the source of development for the entire Nervous system.

On the 20th day, the trunk fold forms, causing the embryo to separate from the yolk sac, and the embryonic endoderm rolls into the gut tube.

After the 20th day, the mesoderm undergoes differentiation, dividing into somites, nephrotomes (segmental intermediate mesoderm), and splanchnotomes (lateral plate mesoderm).

The notochordal process regresses.

The chorion is a set of villous proliferations of the trophoblast consisting of two structural components: epithelium and extraembryonic mesoderm (mesenchyme). Initially, these proliferations form over the entire surface of the trophoblast and are designated as primary villi. Subsequently, in the region of the chorion facing the uterine wall, the villi undergo intensive development, becoming numerous and branching, and are termed secondary villi. They contain Connective tissue with Blood Vessels. From this point on, the chorion divides into two regions: the villous chorion (*chorion frondosum*) and the smooth chorion (*chorion laeve*). The placenta is formed within the area of the villous chorion. Umbilical vessels emerging from the embryo's body via the connecting stalk grow into the chorion and branch within it. The villus is covered by trophoblastic epithelium — cytotrophoblast and symplastotrophoblast. In the placenta, a fetal part (*pars fetalis*), formed by the chorionic villi, and a maternal part (*pars materna*), consisting of a heavily modified region of the uterine mucosa — the basal endometrium (*stratum basale endometrii*) — are distinguished.

Fig. 86. Human embryo at 11.5 days of development:

1 — epithelium of the uterine mucosa; 2 — connective tissue layer of the uterine mucosa; 3 — primary villi; 4 — lacunae in the uterine mucosa filled with blood; 5 — syncytial part of the chorionic epithelium (symplastotrophoblast); 6 — cellular part of the chorionic epithelium (cytotrophoblast); 7 — extraembryonic mesoderm (mesenchyme); 8 — endoderm; 9 — ectoderm; 10 — amniotic vesicle

The placenta performs various Functions: trophic, excretory, respiratory, and barrier. It also acts as an immune defense organ and an endocrine organ, producing Hormones such as human chorionic gonadotropin, progesterone, somatotropin, and mammotropin.

The yolk sac (saccus vitellinus) is formed from the extraembryonic endoderm of the yolk vesicle and the extraembryonic mesoderm. Since human development takes place within the mother's organism, it loses its trophic function. Hematopoiesis occurs within its wall. It functions as a hematopoietic organ until the 7th–8th week, after which it undergoes involution. Primordial germ cells (gonoblasts) are formed in the wall of the yolk sac and migrate from it via the bloodstream to the primordium of the Gonads.

Fig. 87. Human embryo at 15 days of development:

1 — amniotic vesicle; 2 — yolk vesicle; 3 — embryonic disc; 4 — connecting stalk (amniotic stalk); 5 — chorion (epithelium and connective tissue); 6 — secondary chorionic villi; 7 — extraembryonic mesoderm (mesenchyme)

The allantois is an elongated outgrowth of the foregut endoderm and visceral mesoderm. It is located near the yolk sac and grows toward the chorion along the connecting stalk.

Bending into the connecting stalk, the allantois initially grows laterally to the yolk sac, and then, under the pressure of the amnion walls, is gradually displaced from its original position to the ventral side and approaches the reduced yolk sac. The umbilical vessels are formed within the wall of the allantois, with their terminal branches located in the stroma of the villi. The reduced yolk sac, together with the allantois and umbilical vessels, passes through the umbilical cord, which lengthens significantly as the embryo grows. Subsequently, the umbilical cord contains only the umbilical Arteries and Veins, which connect The Vascular System of the embryo with the maternal Circulation.

The amnion is formed by the extraembryonic ectoderm and extraembryonic mesoderm of the amniotic vesicle. It increases in size very rapidly, and by the end of the 7th week, its connective tissue comes into contact with the connective tissue of the chorion. The amniotic epithelium extends onto the connecting stalk, which later transforms into the umbilical cord.

The amniotic membrane forms the wall of the cavity containing the fetus. The cavity is filled with fluid produced by the ectodermal cells of the amniotic membrane facing the amniotic cavity. This fluid (Amniotic Fluid) provides optimal conditions for the free Development of the embryo and maintains the required salt composition and concentration until the end of pregnancy. It protects the fetus from mechanical damage. At the time of delivery, the amniotic membrane creates favorable conditions for the passage of the fetus through the birth canal (uniform dilation of the uterine cervix canal).

Slide 1. Human placenta (Fig. 88).

Low magnification. Locate the fetal part of the placenta and identify the amniotic membrane along the free edge of the organ, which is covered by a simple cuboidal epithelium. Beneath it lies the chorionic plate, formed by connective tissue with large blood vessels. On the side opposite to the amnion, villi extend from the chorionic plate. In cross-sectioned villi, the symplastotrophoblast is located peripherally as dark purple areas containing clusters of nuclei. Internal to the symplastotrophoblast lies the cytotrophoblast, consisting of a single layer of cells. The core of the villus is formed by connective tissue containing blood vessels filled with embryonic blood. Externally, the villi are covered by an amorphous oxyphilic mass—fibrinoid. Lacunae filled with maternal blood are located between the villi.

Locate the maternal part of the placenta, specifically the basal decidua (basal plate), which is situated along one of the free edges of the placenta and represented by a layer of Fibrous connective tissue. Connective tissue septa extend from it into the spaces between the chorionic villi. Within the connective tissue, identify decidual cells—large cells with distinct boundaries, round nuclei, and oxyphilic cytoplasm, located among cell clusters.

Fig. 88. Human placenta. Hematoxylin and eosin staining:

1 — chorionic villi; 2 — symplastotrophoblast; 4 — cytotrophoblast; 4 — basal plate; 5 — lacunae with maternal blood; 6 — septa; 7 — decidual cells

Label on the figure: 1) chorionic plate; 2) chorionic villi; 3) symplastotrophoblast; 4) cytotrophoblast; 5) basal plate; 6) lacunae with maternal blood; 7) septa; 8) decidual cells.

Slide 2. Umbilical cord (Fig. 89).

Low magnification. Locate the amniotic membrane covering the outer surface of the umbilical cord, which is represented by a simple squamous epithelium. Internal to the amniotic epithelium is mucous connective tissue (Wharton's jelly), containing two umbilical arteries and one umbilical vein.

Label on the figure: 1) amniotic epithelium; 2) Wharton's jelly; 3) umbilical arteries; 4) umbilical vein.

Slide 3. Mammary gland during Lactation (Fig. 90).

Low magnification. Locate the lobules of the gland, which are composed of clusters of terminal secretory units. They are separated by interlobular septa formed by wide layers of loose fibrous connective tissue. The lobules contain numerous alveoli with cavities of various SHAPES AND SIZES. Mammary ducts lined with cuboidal and columnar epithelium are present within the lobules and interlobular septa.

Fig. 89. Umbilical cord. Hematoxylin and eosin staining:

1 — amniotic epithelium; 2 — Wharton's jelly; 3 — umbilical arteries; 4 — umbilical vein

High magnification. Locate the lactocytes with round nuclei within the alveoli, as well as myoepithelial cells, which are identified by their rod-shaped nuclei located on the outer surface of the alveoli.

Fig. 90. Mammary gland during lactation. Hematoxylin and eosin staining:

1 — secretory end piece; 2 — myoepithelial cell; 3 — connective tissue septa; 4 — interlobular lactiferous duct

Label the following on the figure: 1) gland lobule; 2) secretory end piece; 3) myoepithelial cell; 4) connective tissue septa; 5) interlobular lactiferous duct.

Review Questions

1. Characterize the periods of human prenatal development.

2. The mechanism of fertilization.

3. Cleavage. The mechanism of cleavage.

4. Formation of the blastocyst.

5. Implantation.

6. Formation of the embryoblast.

7. Trophoblast.

8. Gastrulation and its phases.

9. Chorion.

10. Allantois.

11. Amnion.

Situational Problems

1. During an abortion, an embryo was removed that resembles a vesicle whose wall is formed by a layer of flattened cells. At one of the poles, a group of rounded cells in the form of a nodule is attached to them, bordering an eccentrically located cavity. Determine the stage of embryonic development and the gestational age.

2. During early embryonic development, at the blastocyst stage, the embryoblast divided into two compact groups. What will be the outcome of the further development of the embryo?

3. During the implantation of the embryo into the uterine mucosa, a layer of flattened cells formed at its embryonic pole, topped by large multinucleated structures. Name the stage of embryonic development and its subsequent pathway in humans. Which structures in the embryonic wall differentiate during this period?

4. In the caudal region of the embryo, the wall of the intestinal tube forms an evagination composed of endoderm and the visceral layer of the mesoderm. Name the extraembryonic organ being formed. What functions will it perform?

5. At the beginning of the 2nd week of development, cleft-like spaces form between the cells of the human embryoblast, which later merge into a single cavity. Name the stage of embryonic development and the primordium of the extraembryonic organ forming during this period.

6. At a certain stage of human development, a specific functional connection is established between the maternal and fetal vascular systems. What organ provides this connection, and from which week of pregnancy does it function?

Sample Examination Questions

1. Stages of embryogenesis. Fertilization and cleavage in humans. Blastocyst.

2. Gastrulation in humans. Significance of this process.

3. Features of human development during the 2nd and 3rd weeks of embryogenesis.

4. Amnion. Formation, structure, and significance.

5. Chorion. Formation, structure, and significance.

6. Yolk sac and allantois. Formation, structure, and significance in vertebrates and humans.

7. Human placenta. Its development, structure, and functional significance.