Early Embryonic Development

Iin Novita Nurhidayati Mahmuda

Oogenesis

Gonadotropin

FSH : Follicle maturityStimulate maturation of granulosa cells which produce estrogen

Estrogen

Cause endometrium enter proliferative phase

Thinning of cervical mucous to allow passage of sperm

Stimulate pituitary gland to secrete LH

LH

Causing oocyte finish meiosis I and enter meiosis II

Stimulate production of progesteron Cause follicular rupture and

ovulation

Ovulation

LH surge In digestion collagen fibers

surrounding follicle Local muscular contractions in

ovarian wall Extrude the oocyte with some of the

cumulus oophorus which form corona radiata

Spermatogenesis

Sperm transport The cervix The uterus Isthmus uteri The oviduct

Each of which eliminate proportion of the original population of sperm

To under go fertilization one sperm must undergo capasitation and acrosome reaction

Fertilization The phases of

fertilization :Penetration of the corona radiataPenetration of the zona pellucidaFusion of the oocyte and sperm cell membrane

Fertilization Sperm produces hyaluronidase to penetrate the

follicular cell layer of the corona radiata (see diagram below). It will then interact with only one of many receptors.

At a ZP3 receptor, the head of the sperm releases its contents (acrosin) and burrows through the zona pellucida and perivitelline space - the acrosomal reaction.

Once a receptor has been activated, a series of reactions to prevent polyspermy (the entrance of more than one sperm).will be initiated. First, the cell surface will be depolarized. Then, cortical granules (lysosomes) released into the perivitelline space will hydrolyze the other receptors. Thus, if all functions properly, only one sperm can enter the ovum since only one receptor can be activated.

Fusion of the plasma membranes of the oocyte and sperm occurs; the sperm nucleus is released into the cytoplasm of the oocyte; the rest of the sperm degenerates

Entrance of sperm into the oocyte causes the secondary oocyte to complete its second meiotic division (2 polar bodies at this point)

Male pronucleus forms and swells; pronuclei membranes become porous

Membranes breakdown, chromosomes condense and 46 chromatids line up on metaphase plate in preparation for mitosis

The main result of fertilization

Restoration of diploid number ofchromosomes

Determination of sex Inisiation of cleavage

Masa intrauterine 1. Masa embrional

Meliputi masa pertumbuhan intrauterin sampai dengan usia kehamilan 8 minggu, di mana ovum yang dibuahi (zygote) mengadakan pembelahan dan diferensiasi sel-sel menjadi organ-organ yang hampir lengkap sampai terbentuk struktur yang akan berkembang menjadi bentuk manusia. Proses pembentukan organ "dari tidak ada menjadi ada" ini (organogenesis) pada beberapa sistem organ, misalnya sistem sirkulasi, berlanjut terus sampai minggu ke-12, sehingga beberapa sumber mengklasifikasikan pertumbuhan masa embrional sampai dengan minggu ke-12 (trimester pertama kehamilan). 2. Masa fetal Meliputi masa pertumbuhan intrauterin antara usia kehamilan minggu ke 8-12 sampai dengan sekitar minggu ke-40 (pada kehamilan normal / aterm), di mana organisme yang telah memiliki struktur lengkap tersebut melanjutkan pertumbuhan dan perkembangan yang pesat, sampai pada keadaan yang memungkinkan untuk hidup dan berfungsi di dunia luar (ekstrauterin).

Week I

Fertilization Cleavage Formation of the blastocyst Differentiation into cytotrophoblast

and syncytiotrophoblast

Cleavage

Following mitosis, two blastomeres form, each one totipotent (capable of forming its own organism)

Continuing along the uterine tube, the zygote divides to four, then eight cells

Size of individual blastomeres decreases with progressive divisions as zygote maintains size

A ball of 12 or more cells, the morula, enters the uterus around day 3

Formation of the blastocyst Compaction: Blastomeres

clump together; the amount of cytoplasm is reduced

Adhesion: E-cadherin gene is expressed; these proteins facilitate intercellular adhesion and communication

Zona pellucida is shed, allowing for cell growth and for uterine fluid to infiltrate

A fluid-filled cavity (blastocoele) forms in the center, pushing cells to the periphery

The outer cell layer, the trophoblast ("tropho" - to nourish), may have a nutritive role as the future embryonic part of the placenta

The inner cell mass, the future embryo, forms as a ball of cells on one side of the spherical blastocyst

Differentiation into cytotrophoblast and syncytiotrophoblast

Near the end of the first week, the blastocyst implants in the posterior wall of the uterus in the presence of high hormone levels; the blastocyst attaches at the embryonic pole (inner cell mass) so the embryo will eventually be attached dorsally. Occasionally, the blastocyst will implant on another spot in the uterus, potentially causing problems (see placenta previa).

The trophoblast layer undergoes mitosis upon contact with the uterine wall and differentiates into the cytotrophoblast ("cellular" layer) and the syncytiotrophoblast ("multinucleated" layer).

WEEK 2

Late implantation/Uteroplacental circulation

Bilaminar disk, amniotic cavity and primary yolk sac

Extra-embryonic mesoderm and coelom

Formation of the chorion and definitive yolk sac

Late implantation/Uteroplacental circulation

Day 8 - The syncytiotrophoblast begins to invade the capillaries, glands and connective tissue of the endometrial wall of the uterus

Day 9 - Spaces known as lacunae form in the syncytiotrophoblast; they fill with maternal blood and glandular fluid

A closing plug covers the defect in the endometrial epithelium caused by implantation of the blastocyst; the epithelium will be regenerated by day 12

A network of lacunae form (spaces in the placenta filled with maternal blood that comes into contact with fetal villi)

Days 11-12 - primitive utero-placental circulation forms with oxygenated maternal blood arriving via spiral arterioles, seeping into lacunae and leaving via endometrial venous capillaries.

Days 13-14 - primary chorionic villi develop, will eventually become vascularized

Note the multinucleated synctiotrophoblast and the cellular cytotrophoblast, the bilayered embryonic disk, and the amniotic cavity (outlined in blue). At this point, the syncytiotrophoblast has undergone mitosis to erode the uterine endometrium. The maternal capillaries thus begin to supply the embryonic tissues with oxygenated blood (as demonstrated by red arrows).

Bilaminar disk, amniotic cavity and primary yolk sac

During implantation, a cavity appears in the inner cell mass; amnion forms around this amniotic cavity; derived from amnioblasts from the epiblast

Cells of the embryonic disc flatten and differentiate into two layers:-epiblast - a tall, columnar layer of cells forming the "floor" of the amniotic cavity (primitive ectoderm)-hypoblast - a short, cuboidal layer of cells forming the "roof" of the exocoelomic cavity (primitive endoderm)

The exocoelomic cavity and membrane form the primary yolk sac

Thus, bilaminar embryonic disk is sandwiched between two "balloon-like" cavities, the amniotic cavity and the primary yolk sac

Extra-embryonic mesoderm and coelom

Cells derived from the primitive ectoderm fill the space between the trophoblast and two cavities

This loose connective tissue, the extraembryonic mesoderm, completely surrounds the amnion and primary yolk sac

Fluid-filled spaces appear in the mesenchyme, pushing aside the mesenchyme to form a coelom

Formation of the chorion and definitive yolk sac

Endodermal cells from the hypoblast migrate to the primary yolk sac

As the extraembryonic coelom grows, the large primary yolk sac pinches off, leaving behind a smaller, secondary yolk sac which is "permanent"

  The embryo, surrounded by two cavities, floats in a large "bubble" (future chorionic cavity)

WEEK 3

Gastrulation: Primitive Streak and Cell Migrations

Results of Gastrulation: Fate of the Germ Layers

Notochord: the Primary Inducer Neurulation: Neural Tube Formation Neural Crest Cells and their Derivati

ves

The third week is characterized by early morphogenic changes as the bilaminar embryo is transformed into a trilaminar embryo, developing the three cell lineages that will eventually form every system.

It is also the time of early tissue and organ differentiation of the nervous and cardiovascular systems, as well as the formation of future body cavities.

Gastrulation: Primitive Streak and Cell Migrations

The primitive streak appears on the epiblast surface, migrating caudally from the primitive node (Hansen's node) to the cloacal membrane where it stops; it grows by the addition of cells at the "tail" end

Embryonic orientation established: cranial/caudal since primitive streak migrates caudally, right vs. left, and dorsal vs. ventral since primitive streak occurs on dorsal side

Cells migrate from the epiblast to the middle layer between it and the hypoblast; forming intra-embryonic mesenchyme (loose embryonic connective tissue)

Mesenchymal cells migrate from primitive streak cranially to form 1)cardiogenic mesenchyme (most cranial point), 2)the notochordal process (also in the cranial direction), and 3)lateral mesenchyme (to the lateral edges where it meets with extra-embryonic mesenchyme)

The length of the primitive streak will decrease as the notochord increases and it will eventually degenerate, so that the caudal end of the embryo will decrease in size

If the primitive streak does not degenerate, this undifferentiated tissue could result in a sacro-coccygeal teratoma.

Results of Gastrulation: Origin and Fate of the Germ Layers

All three germ layers are derived from the epiblast.

Fate of the Germ Layers

ENDODERM :  epithelial lining of respiratory and GI tract  MESODERM :  cardiovascular system, reproductive/excretory

organs, smooth and striated muscle, connective tissues, vessels, skeleton 

ECTODERM : SURFACE ECTODERM - epidermis, and other external structuresNEUROECTODERM - central and peripheral nervous system, neural crest cells and derivatives

Epithelium is derived from all three germ layers - ex. endoderm - epithelial lining inside viscera, mesoderm - mesothelium lining outside of viscera, and ectoderm - skin epithelium

Notochord: the Primary Inducer The notochordal process develops by the

migration of mesenchymal cells cranially from the primitive node, eventually stopping at the bucco-pharyngeal membrane (a bilayer disk of endoderm/ectoderm)

The floor of the notochordal process fuses with the intra-embryonic endoderm of the yolk sac

The fused layers degenerate temporarily to form a transitory communication with the yolk sac (neurenteric canal)

 The notochordal plate folds inward, to form a rod-shaped notochord; cell proliferation occurs cranially to caudally

As the notochord closes as a tube, it detaches from the endoderm of the yolk sac

It is now located in the mesoderm, between the endoderm and ectoderm

Functions of the Notochord:1. Structure - acts as a rigid axis around which the embryo develops2. Skeletal - foundation upon which the vertebral column (vertebral bodies) will form*3. Induction - will bring about formation of the neural tube (future nervous system)*

Fate of notochord: It will eventually break up into section of weight-bearing intervertebral disks, known as the nucleus pulposos (this little structure may give rise to what is commonly known as a "slipped disk”. A tumor can occur here, known as a chordoma, localized in the intervertebral disk, capable of causing nerve damage.

Neurulation: Neural Tube Formation Neurulation includes the

formation of the neural plate (day 18-19), neural folds (day 20-21), and the neural tube (day 22-26); the latter will develop into the future brain and spinal cord

The neural plate forms as a central strip of surface ectoderm cells, just above the notochord. It is induced to become neuroectoderm through changes in cell shape (cuboidal to columnar) and proliferation; the cells develop N-CAM adhesion molecules, disorganized filaments and elongated tubules; this flat layer of cells is referred to as the neural plate

The layer of cells between the regular surface ectoderm and the neuroectoderm possess characteristics of both cell types, such as the possession of both L-CAM (ectoderm) and N-CAM (neuroectoderm) adhesion molecules, and are called neural crest cells.

At the neural plate, the cells continue to morph into pyramidal shaped cells with straight neuro-tubules, neuro-filaments concentrated at the apex of the cell, connected by desmosomes

The change in cell shape and a decrease in cell number cause the neuroectodermal cells to gradually fold inward, forming neural folds (d 20-21)

The neural tube continues to grow in this manner, and eventually breaks free of the surface ectoderm which will be sealed off. Up to this point, it was supplied continuously with amniotic fluid.

As the neural tube forms, the closing process is critical, occurring from the cranial to the caudal end as the anterior neuropore closes around day 24, the posterior around day 26. This is a critical event, as defects in closure may result in spina bifida or other neural tube defects. The risk of a neural tube defect can be decreased by folic acid supplements, a campaign led by the March of Dimes.

The neuroepithelial cells at this stage are bipotential, capable of forming neurons or neuroglial cells.

Once the neural tube has closed completely, vertebral structures develop around it, as do meninges and finally, skin from the surface ectoderm

Review: The notochord is of mesenchymal origin. During formation, it is continuous with embryonic endoderm, allowing for the neurenteric canal between the amniotic and yolk sac cavities. The notochord then detaches from the endoderm to form a closed tube in the mesoderm. On the other hand, the neural tube originates from the ectodermal layer, when the surface ectoderm is induced by the notochord to form neuroectoderm. Thus, the neural tube begins its development intercalated in the primitive ectoderm but, like the notochord, eventually detaches to form a closed tube.

Neural Crest Cells and their Derivatives

As the notochord induces the transformation of surface ectoderm to neuroectoderm, a multipotential middle cell layer develops with characteristics of both cell types (N-CAM and L-CAM adhesion molecules) as well as important future roles.

These neural crest cells migrate dorsolaterally to form the neural crest, a flattened irregular mass between the surface ectoderm and neuroectoderm

This layer will separate into right and left portions and then migrate to different areas (Take some time to become familiar with these now, because they will come back in future units!)

Note: Failure of neural crest cells to migrate will result in anomalies such as albinism, "elephant man," or oropharyngeal teratoma. Remember, teratomas form from disorganized, multipotential tissues such as the primitive streak, neural crest cells and primary germ cells.

Derivatives of Neural Crest Cells

Spinal ganglia (prevertebral/paravertebral)

Ganglia of the autonomic nervous system (ANS)

Ganglia of cranial nerves V, VII, IX, XSheaths of peripheral nerves

Meningeal coverings of brain and spinal cord

Pigment cells (melanocytes)Adrenal medulla

Odontoblasts of toothOther components of head

WEEK 4

Somite development Intraembryonic coelom & body

cavities Head-tail folding Lateral folding

In week 4, the embryo undergoes major morphological changes as it changes from a trilaminar disk-shaped embryo to a cylindrical embryo. This is also an important week in terms of determining placement of future organs. Following median and horizontal folding, many organs and body cavities will begin to form or will be repositioned.

At the beginning of week 4, the embryo is 2.0-3.5 mm long, straight, has 4-12 somites, and a neural tube that has begun to close at the cranial end (rostropore). Somites will continue to develop, increasing in number to 20-30 during this week, the somite period of development. They can be visualized on the surface of the embryo and are used to estimate the age of the embryo. They will eventually give rise to the vertebrae, ribs, and musculature of the axial skeleton, as well as the dermis.

Somite development At the end of week 3, the intra-

embryonic mesenchyme differentiates into three loose aggregate pairs of mesenchyme on each side of the neural tube

Medially, the paraxial mesoderm differentiates into the future dermatome (dorsal surface), myotome (middle layer), and sclerotome (ventral layer), forming dermis, muscle, and connective tissue respectively. Moving laterally, the second aggregate pair, called the intermediate mesoderm, will form the future urogenital system. Most laterally, the lateral plate mesoderm will develop into future body cavities (intraembryonic coelom) and parts of the body wall.

The paraxial mesoderm will develop into paired cuboidal bodies, or somites (Gr. soma, body). These will eventually develop into the bones (sclerotome), muscles (myotome), and dermis (dermatome) of and surrounding the axial skeleton. Somites appear as bumps on the dorsal surface of the embryo.

At the end of week 3, 4-12 somites are present (visible on the dorsal surface of the embryo). By the end of week 5, 42-44 can be counted. However, most appear between days 20-30, giving this period the title of the somite period of development.

Somites appear cranially to caudally, beginning at the occipital end. They can be counted and are used to roughly estimate the age of the embryo.

Dorsal View of an Embryo at about 22 days (8 somite stage)

Eventually, they play a major role in segmentation of the embryo and the adult. Since several somites will disappear, the final number is 31 pairs of somites.

Law of Original Innervation: The myoblasts (future muscle cells) form concurrently with the spinal nerves and they migrate out from the notochord together. This results in the formation of 31 spinal nerves with associated skin, muscle, and connective tissue.

The Intra-embryonic Coelom and Future Body Cavities

At the end of week 3, spaces in the lateral plate and cardiogenic mesenchyme fuse to form a horseshoe-shaped intra-embryonic coelom (same process of development as the extra-embryonic coelom). Amniotic fluid can then circulate in this area, as it communicates with the extra-embryonic coelom.

 The curve of this horseshoe will form the pericardial cavity and the limbs will form the future pleuroperitoneal cavities.

The curve of this horseshoe will form the pericardial cavity and the limbs will form the future pleuroperitoneal cavities.

In the fourth week, the horseshoe will change to a pericardial cavity, with two symmetrical pericardioperitoneal canals, leading to the large peritoneal cavity.

The future body wall is formed on the dorsal surface of the cavity of somatic mesoderm from the lateral plate, mesothelium, and surface ectoderm. The future gut wall is formed from lateral plate mesoderm, mesothelium and endoderm on the ventral surface of the intra-embryonic coelom. During this week, the embryo will fold laterally, so the outer somatopleure envelops the inner splanchnopleure.

The three body cavities (pericardial, pleural, peritoneal) will form definitively in the second month.

Head-Tail Folding Due to the rapid

growth in the median plane of the brain, amniotic cavity, and somites, the embryo elongates, with its head and tail ends folding under.

At the cranial end, the head will be folded under, with a very prominent forebrain. Just cranial to it, on the ventral side, will lie the newly positioned primitive heart, pericardial cavity, septum transversum, and bucco-pharyngeal membrane.

Longitudinal section of an embryo about to undergo head-tail folding

During this fold the future body cavities of the intra-embryonic coelom will find their future locations and the foregut will form from the endoderm of the yolk sac, resulting in a reduced yolk sac.

At the tail end, the endoderm of the yolk sac is incorporated into the embryo to form the hindgut region. The connecting stalk is now attached ventrally, with the allantois jutting into the embryo.

Lateral Folding At the same time that head-tail

folding is occurring, lateral folding is also occurring to form a cylindrical embryo.

The layers of the somatopleure surrounding the amnion grow downwards to enclose the gut with its splanchnopleure.

The endoderm of the yolk sac forms the future midgut, connected to the yolk stalk.

The folding results in the formation of the umbilical cord, amniotic epithelium surrounding all the middle layers that were enclosed during the folding process (extra-embryonic mesencyme primarily, also part of the yolk sac, allantois and extra-embryonic coelom) 

Resume 3rd week-8th week (the embryonic period)

The period during which each of the three germ layers ectoderm, mesoderm, endoderm gives rise to its own tissues and organ systems.

As the result of organ formation, major feature of body form are established