The First Three Weeks of Human Embryogenesis Department of Histology, Cytology and Embryology Kharkiv State Medical University

Week 1-3: Early Stages: 1. Fertilization 2. Cleavage 3. Gastrulation 4. Formation of the embryo body Late stages: Histogenesis, Organogenesis

Week 1 1.Fertilization – is the fusion of the sperm and ovum = Zygote formation

Fertilization. Cleavage 2 cells stage 3-5 cells stage Morula Blastula . . uterus uterine tube Implantation Day 6 - 8 Fertilization (positive rheotaxis, gyno-androgamones, capacitation, acrosomal reaction) = zygote

Week 1 2.Cleavage – is the division of the zygote in the uterine tube = Blastula formation (2 cell stage – 4 cell stage …16-32 cell stage (morula) – blastocyst) During cleavage the germ is moved to the uterus

At the end of the cleavage outer cells (trophoblast) involve nutritive fluid, which forms cavity, moving inner cells to the periphery (embryoblast). Blastula is formed. Inner Cell Mass (embryoblast) Trophoblast Blastocoele

Week 2. 3. Gastrulation Gastrulation by the delamination and migration leads to formation of three germ layers: ectoderm, endoderm and mesoderm, and axial organs: notochord, neural tube, somites

Early Gastrulation. At the beginning of gastrulation germ sinks into the uterine wall – implantation. Gastrulation begins from delamination – division of embryoblast into two germ layers - ectoderm and endoderm, forming embryonic disc and two sacs – ectoblast and endoblast

Delamination Trophoblast Ectoblast Embryonic disc: Ectoderm Endoderm Endoblast

Migration - extraembryonic mesoderm formation From embryonic disc cells begin to migrate which form extraembryonic mesoderm, surrounding upper and lower sacs, and underlying trophoblast As a result appear amnion, yolk sac and chorion (extraembryonic organs)

Week 2 Extraembryonic Mesoderm Trophoblast Chorion Ectoderm Amnion Endoderm Yolk Sac

Late gastrulation – migration continues within embryonic disk and leads to formation of the embryonic mesoderm (third germ layer) and axial organs (neural tube, notochord and somites - 43, 44 pairs)

Transverse section. Moving ectodermal and endodermal cells form group of cells = primitive streak Amniotic Cavity Embryonic mesoderm Ectoderm Primitive streak Yolk Sac Endoderm

Notochord is formed from invaginated ectoderm and primitive streak

Notochord formation (longitudinal section)

Development of the Neural Tube by the invagination of ectoderm

Development of the Neural Tube Neural groove Thus, the cells can become pyramidal in shape, and this change in cell shape can alter a flat sheet of cells to become a hollow tube.

Development of the Neural Tube

Development of the Neural Tube It is known that the notochord and the adjacent mesoderm around it can induce the ectoderm above to form the neural tube.

Development of the Neural Tube Surface Ectoderm During the formation of the neural tube, ectodermal cells that are at the junction of the neural plate with the surface ectoderm, form neural crest cells. Neural Crest Neural Tube

Neural tube formation

Neural tube formation

Somites locate between ectoderm and endoderm, arise from primitive streak and notochord and consist of mesoderm

Axial organs –neural tube, notochord, somites (mesoderm)

Formation of the Body Axis Left – Right Sidedness FGF8 Nodal Lefty PITX2

Left – Right sidedness Situs inversus 20% (Kartagener syndrome) Dysfunctional cilia Respiratory problems Male fertility problems

Body flexion, head and tail folds formation. 4. Formation of the embryo body (20 days) Body flexion, head and tail folds formation. Amnion accumulates fluid and increases, yolk sac decreases. Formation of a gut, allantois

Body flexion formation

Body flexion formation (Gut formation Body flexion formation (Gut formation. The upper part of yolk sac forms tube inside the forming body = gut - primitive digestive tube gut

(Gut. Allantois – is extention of hindgut) Body flexion formation (Gut. Allantois – is extention of hindgut) Allantois FUTURE PLACENTA

Body formation hindgut foregut midgut Cloacal Plate Oral Plate Allantois Heart Yolk Sac

Body formation Chorionic plate participates in the formation of placenta Amniotic cavity Uterine Wall Chorionic Cavity Yolk Sac and allantois participate in the formation of ambilical cord

What should we study by heart ?

EXTRAEMBRYONIC ORGANS chorion Amnion Allantois FUTURE PLACENTA Yolk sac

Extraembryonic organs (supportive, nutritive) Amnion – protective bag of water Yolk sac – gut, germs of gametes first blood vessels, cells Allantois – urinary bladder Chorion – protection, hormones, placenta Placenta – main nutritive, protective, hormonal

Differentiation of GERM LAYERS: 1. Differentiation of Ectoderm A. Surface Ectoderm B. Neural Tube 2. Differentiation of Endoderm A. G.I. Tract B. Respiratory Tree C. Endocrine glands 3. Differentiation of Mesoderm A. Somites-dermatome, myotome, sclerotome B. Intermediate- nephrotome C. Lateral-splanchnotome D. Mesenchyme

Surface Ectoderm differentiates to skin, its derivatives, oral, rectal epithelium, corneal epithelium, tooth enamel amnion ectoderm proctodeum stomatodeum

Ectoderm forms neuroectoderm –neural tube (neurons and neuroglia of the brain and the retina) and neural crests (nerve ganglia, neuroglia, adrenal medulla, melanocytes, APUD-system).---15-20 weeks Surface Ectoderm During the formation of the neural tube, ectodermal cells that are at the junction of the neural plate with the surface ectoderm, form neural crest cells. Neural Tube Neural Crest

Endoderm differentiates to epithelium of the stomach, intestine, liver, pancreas, respiratory, endocrine systems -- 3-4 weeks - gut endoderm gut

Endoderm (gut, allantois) foregut hindgut midgut Heart Cloacal Plate Oral Plate Stomatodeum Allantois Yolk Sac

Mesoderm - formation of the first blood vessels in the wall of yolk sac and allantois

Mesoderm Ectoderm (Somite) Amniotic Cavity Intermediate mesoderm (nephrotome) Lateral plate mesoderm (somatopleuric, splanchnopleuric mesoderm) Amniotic Cavity During the third week of development the mesoderm on either side of the notochord thickens and is called the paraxial mesoderm. The paraxial mesoderm gives rise to somites. Laterally, the mesoderm is thin and is called the lateral plate mesoderm. A cavity develops in the lateral plate mesoderm that is continuous with the extraembryonic coelom, called the intraembryonic coelomic cavity. This cavity divides the lateral mesoderm into two layers. The mesoderm that lies dorsal to the intraembryonic coelomic cavity is called the somatic (parietal) mesoderm. The ectoderm and somatic mesoderm is called the somatopleure. That mesoderm found ventral to the intraembryonic coelomic cavity is called the splanchnic (visceral) mesoderm. The splanchnic mesoderm and the endoderm is called the splanchnopleure. The mesoderm between the paraxial and lateral plated mesoderm is called the intermediate mesoderm. Yolk Sac Notochord Endoderm

Mesoderm dermatome - dermis of skin myotome - muscles, Somite sclerotome - skeleton, except skull Mesoderm Somite urogenital system including kidneys, gonads, ducts, and accessory glands Intermediate Mesoderm. Nephrotome Lateral Mesoderm - serous membranes of pleura, pericardium and peritoneum Mesenchyme (loose part) – connective tissue of viscera and limbs, blood and lymph cells, cardiovascular and lymphatic systems

Chorionic plate participates in the formation of placenta Amniotic cavity Uterine Wall Chorionic Cavity Yolk Sac and allantois participate in the formation of ambilical cord

Late embryonic stages Histogenesis Organogenesis