Embryology Made Ridiculously Simple by Aya

Musbahi“It is not birth, marriage or death but

gastrulation that is the most important time in your life” Lewis Walpert 1986

It is the time that elapses between fertilisation and the birth of a new individual. It is about 9 calendar months.

The intra-uterine life of the individual is divided into 3 stages.

Stage1- Germinal Period- 1st 2 weeks Stage 2- Embryonic Period- 2nd week to 3rd

month Stage 3- Foetal Period-3rd month to 9th

month

The Intra-uterine Life:

Fusion of the male and female gametes happens in the Fallopian tube Egg complex is surrounded by cells called the Corona Radiata and a

Zona Pellucida Radiata is penetrated by sperm and reaches the ZP Three glycoproteins make up the ZP, 1, 2 and 3 Initially, the sperm binds to ZP3 Liberation of enzymes found in sperm sac called acrosome In the acrosome are acid proteinase, collagenase, acrosin amongst

others Zona Pellucida binding stimulates this release of enzymes from the sac Acrosomal reation is the name given to this process and it helps the

sperm to get through the ZP. Tail of the sperm also propels it forward Influx of Calcium into the sperm head assist this process One plasma membrane is formed by fusing the sperm and egg

membranes Nuclei (haploid/pronuceli) of both join up to form diploid egg.

FERTILIZATION: 

Definition: The fusion of male and female gametes

Site: Lateral 1/3 of the Fallopian tube Mechanism: The fertilising sperm pierces

the corona radiata and Zona Pellucida. The head detaches from the rest of the sperm and forms the male pronucleus which contains half the number of chromosomes. The nucleus of the ovum is also haploid and both fuse to form a dilpoid zygote.

So in Summary:

There is a ball covered in velcro and a needle and syringe which is to be inserted into the balloon. The ball is like the ovum and the needle is the sperm and the velcro is the Zona Pellucida.

 The ball has been on the floor for a long time and stuck to the velcro is a lot of fluff from the rug (fluff is the corona radiata). We need to insert the needle through the velcro and into the balloon. So we need to remove the fluff first (corona radiata). The needle needs to then get through the velcro (the ZP) before it gets to the balloon. It attaches to the velcro first (to ZP3) and then penetrates it. In the syringe attached to the needle is a potent acid. We're going to use the syringe and needle to release some acid to dissolve the velcro (the acid in the syringe is like the acrosomal sac contents), so we can penetrate the ball.

Analogy:

Describe the Essential Steps in fertilisation. Describe cellular events in fertilisation. 

Buzz Words: Zona Pellucida, Corona Radiata, ZP3,

Acrosomal Reaction, Fusion, Pro-nuceli

Past Paper Questions (Medicine):

What happens next to the embryo, is very interesting and fast paced.

The Embryo- An autobiography

EMBRY O’ In My mother’s womb…..

THE AUTOBIOGRAPHY

Cleavage

Definition: a series of mitotic divisions occurring in the zygote. Each cell that results is called a blastomere.

Site: these divisions occur in the zygote as it passes in the fallopian tube to reach the uterine cavity.

Cleavage Division

The 2 cell stage appears at 30 hours after fertilisation The 4 cell stage appears at around 45 hours after fertilisation The Morula is the 12-16 cell stage and appears about 3rd

day The cells become arranged into an inner cell mass in the

centre and an outer cell mass in the periphery The Blastocyst develops on the 4th day As the cells of the morula continue to divide, fluid from the

uterine cavity enters the spaces between the cells. These fluid filled spaces join together to form one large

cavity called a blastocele and the morula is now called a blastocyst.(the Zona Pellucida disappears completely at day 4)

On the 6th day

 Steps:

The cells of the outer cell mass form the trophoblast- will form foetal membranes later on

The cells of the inner cell mass become located at one pole- called the embryonic pole (the opposite pole is called the abembryonic pole)

The blastocyst attaches to the endometrium at 5-6 days after fertilisation.

Differentiation of the Blastocyst

Definition: It is the penetration of the blastocyst into the superficial compact layer of the endometrium.

Time: Begins day6 or 7 and ends by day 11 or 12.

Site: endometrium of the posterior wall of the fundus of the uterus

Implantation (embedding)

The blastocyst becomes attached to the endometrium by its embryonic pole

The trophoblast cells covering the embryonic pole erode the epithelium of the endometrium (possibly by enzymatic action)to allow the blastocyst to penetrate through the defect.

After complete embedding of the blastocyst, the penetration defect is closed by a fibrin clot.

Implantation is completed by growth of the epithelium to cover the defect.

Steps:

Sixth/Seventh day Fundus of Uterus Embryonic pole attaches Trophoblasts erode endometrium Penetration defect formed Blastocyst enters Embeds completely Closed by a clot Intact epithelium again  Sad Forgotten Emos Try Partying But Eat

Carrots Instead

So in Summary…

The following things happen:1. Implantation: is complete (11th/12th day)2. Trophoblast differentiates into TWO layers

(syncytio-trophoblast and cytotrophoblast)3. Inner cell mass becomes TWO layers (called

bilaminar germ disc and composed of Ectodermal layer and Endodermal layer)

4. TWO cavities are formed (amniotic cavity and the yolk sac)

NB) there is a rapid rate of growth in the second week compared to the first week

Second Week of Pregnancy

The blastocyst is still partially embedded in the endometrium

Inner cell mass forms 2 layers- an inner ENDODERM (hypoblast) (small polygonal cells) and an outer ECTODERM (epiblast) (tall columnar cells).

The trophoblast starts to differentiate into 2 layers: Outer dark zone without cell boundaries called the

SYNCYTIOTROPHOBLAST and an inner pale zone with clear boundaries called CYTOTROPHOBLAST.

An Amniotic Cavity starts to be formed : small clefts appear between the ectodermal cells and the trophoblastthe clefts join each other to form the amniotic cavity. The cytotrophoblast develops a layer of cells called amnioblasts which form the roof of the amniotic cavity, while the floor is formed by the epiblast or ectoderm.

The Eighth Day:

1. lacunae2. endometrium3. syncytiotrophoblast4. cyto-trophoblast5. surface epithelium of the endometrium6. epiblast7. amniotic cavity8. hypoblast

The blastocyst becomes more deeply implanted and the fibrin clot covers the penetration defect.

The trophoblast becomes fully differentiated into cyto and syncytio-trophoblast.

Spaces called lacunae appear in the syncytio-trophoblast.

The amniotic cavity becomes larger A second cavity forms called the Primary Yolk

Sac at the ventral aspect of the embryonic disc. The Primary Yolk sac is the new name for the old blastocyst cavity. Its roof is formed by the endodermal layer of the hypoblast and the rest of its lining is called Heuser's membrane.

9th and 10th days:

The blastocyst is completely embedded by now

Lacunae in the syncytio-trophoblast formed earlier start communicating with each other to form larger spaces. This is a primitive maternal foetal circulation.

11th and 12th days:

Formation of the extra-embryonic mesoderm:

cells of inner surface of the cyto-trophoblast form a loose tissue called extra-embryonic mesoderm

Lots of interesting things happen to the cyto-trophoblast:

1. syncytiotrophoblast2. lacunae3. surface epithelium of the endometrium4. fibrin clot5. epiblast6. amniotic cavity7. hypoblast8. primary chorionic villi/cytotrophoblast9. primary yolk sac

Cavities are formed inside the extra-embryonic mesoderm. These cavities fuse together to form the extra-embryonic coelom. However, the coelom doesn't replace the mesoderm completely, rather it divides it into two, SOMATOPLEURE which lines the cyto-trophoblast and the splanchnopleure which covers the yolk sac.

NB) The connecting stalk is a mass of mesoderm connecting the roof of the amniotic cavity with the trophoblast.

Formation of extra-embryonic coelom:

imagine the extra-embryonic mesoderm is like the a dried up oxbow lake and the yolk sac and amniotic cavity and bilaminar germ disc is an island in the middle. When the water flows in the rainy season. The lake has two river banks or two lake edges on either side. The water is like the extra-embryonic coelom and the banks on either side are the somatopleure (on the outside- has an O) and splanchnopleure (on the inside, has an N). There is a bridge connecting the island to the outer edge/bank. This is the connecting stalk.

ANALOGY:

1. secondary yolk sac 2. remnants of the primary yolk 3. amniotic cavity 4. extra-embryonic coelom 5. epiblast 6. connecting stalk 7. hypoblast 8.syncytiotrophoblast 9. lacunae 10. somatopleure 11. splanchnopleure

The most prominent changes are the appearance of primary chorionic villi as follows:

Parts of the cytotrophoblast at the embryonic pole project into the syncytiotrophoblast forming primary chorionic villi, surrounded by lacunae.

  The primary yolk sac gets smaller and gets

pinched off and is now called the secondary yolk sac.

13th Day:

Week 2 of Pregnancy:2 cavities2 germ cell layers2 trophoblast layers

So in Summary:

INTERACTIVE SESSION: WEEK 2: PUTTING IT ALL

TOGETHER IN A TIMELINE

 Summary:

Changes in the embryonic disc1. Formation of the intra-embryonic mesoderm-

now a TRILAMINAR germ disc2. Formation of the notochord- which is a

temporary supporting structure to the embryonic disc

Changes to the trophoblast (chorion): 3 types of chorionic villi form and cover the whole surface of the chorionic vesicle.

The Third Week:

1. Primitive groove

2. Primitive pit

3. Primitive node

4. Oropharyngeal membrane/Prochordal plate

5. Cardiogenic plate

6. Sectional edge of amniotic membrane

7. Mesoderm

8. Endoderm

9. Future cloacal membrane

Formation of the primitive streak

1. Primitive Groove2. Epiblast3. Extraembryonic mesoderm4. Hypoblast5. Invading epiblast cells

forming intra-embryonic mesoderm

6. Hypoblast again

  Formation of the primitive streak:

At the beginning of the third week, ectodermal cells in the caudal part of the bilaminar germ disc migrate to the midline forming a primitive streak (a narrow midline groove)- basically the cells of the epiblast migrate downwards forming a groove.

Formation of the intra-embryonic mesoderm:

These cells separate from the epiblast (now called ectoderm) and migrate in all directions. This new layer of cells is called the intra-embryonic mesoderm. There is an area in the cranial end that it doesn’t migrate to, that is the propchordal plate and an area called the cloacal membrane, behind the primitive streak. These areas remain BILAMINAR.

Why?

Because mesoderm forms vascular tissue. These bilaminar areas do not have mesoderm so without a blood supply they will break down. This is important as these areas need to break down to form contact with the external environment:

Prochordal plate buccopharyngeal opening

Cloacal membrane anus

Pillow and Pillow Cover. The two pieces of material sewn together to form the pillow cover are the epiblast (ectoderm) and hypoblast (endoderm). When I want to stuff the pillow into the pillow cover, there needs to be an opening, yeh? That opening is like the primitive streak. When I stuff the pillow I make sure the whole of the pillow case is encased with pillow. The stuffing is the mesoderm, the pillow cover represents the ectoderm and mesoderm.

Mnemonic:

Primitive streak, Midline groove of Epiblast cells, forms Mesoderm, Migrates all directions, Trilaminar disc forms

Prime Ministers of England Meet Many Troubles

This whole process of mesoderm formation is called GASTRULATION

Mesoderm components MESODERM: Mesothelium (peritoneal, pleural, pericardial)/

Muscle (striated, smooth, cardiac) Embryologic Spleen/ Soft tissue/ Serous linings/

Sarcoma/ Somite Osseous tissue/ Outer layer of suprarenal gland

(cortex)/ Ovaries Dura/ Ducts of genitalia Endothelium Renal Microglia Mesenchyme/ Male gonad

Why is mesoderm so important?

There is a thickening of the ectoderm at the cephalic end of the primitive streak and the primitive node, remember, is where there is the central depression with the slightly elevated area.

  The cells of this primitive node proliferate and form a

solid rod of cells called notochordal process which grows in a cephalic direction between the endoderm and ectoderm.

  Inside the notochordal process Is a small central

notochordal canal which passes from the primitive pit anteriorly.

Formation of Notochord:

The notochord is a bit like a hollow metal pipe that passes through the pillow we talked about earlier.

The notochord gives the embryo structure and helps it to define its axes.

Changes to the trophoblast in the 3rd week

Formation of the chorionic villi

Primary chorionic villi: begin to appear by the end of 2nd week at the embryonic pole of the chorionic vesicle and increase in number by the beginning of the 3rd week. Each primary villus is made up of a central core of cytotrophoblast and a covering layer of syncytiotrophoblast.

Secondary chorionic villi: by the beginning of the 3rd week, cells from the extra-embryonic mesoderm start to penetrate the primary chorionic villi and forms secondary chorionic villi. Each secondary chorionic villus is made up of a central core of extra-embryonic mesoderm, a middle zone of cytotrophoblast and an outer zone of syncytiotrophoblast.

Tertiary chorionic villi: by the end of the 3rd week, a loop of afferent and efferent capillaries appears in the mesodermal core of the secondary chorionic villi. The afferent one is connected to the umbilical artery and the efferent one is connected to the umbilical vein.

Differentiation of the Intra-embryonic mesoderm:

The mesoderm is formed as a loose tissue between the ectoderm and endoderm by day 17 on either end of the notochord.

As development proceeds, 2 longitudinal grooves appear in the mesoderm on either side of the notochord, dividing it into 3 parts.

After the 3rd Week

Imagine 2 sheets of wood and a pipe between them. The joiner cuts the each piece of wood on either side into 3 parts.

Paraxial mesoderm, on either side of the notochord

About 20th day, transverse grooves appear dividing the paraxial mesoderm into somites (blocks). The first pair form day 20. 3 additional ones form each day from 21st to 30th day i.e. by the end of 1st month, 30 or 31 pairs of somites are formed. B

Day 30-40, rate has slowed and finally 42-44 pairs are formed.

The Three Parts

4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 8-10 coccygeal.

By the end of the 4th week, the somites differentiate, so each somite divides into 2 parts:

A ventro-medial part called the sclerotome (becomes mesenchyme, CT, bone cells)

A dorso-lateral part called dermomyotome (becomes skin and muscles).

Somites

S- structures of the paraxial mesoderm O- occipital to coccygeal M- mesodermal tissue T-TWO parts- ventromedial and dorsolateral E- embryo age can be estimated from

number of somites

Mnemonic

This tissue, which temporarily connects the paraxial mesoderm with the lateral plate

In the cervical and upper thoracicregions it forms segmentally arranged cell clusters (the future nephrotomes), whereas more caudally it forms an unsegmented dmass of tissue known as the nephrogenic cord. From this partly segmented, partly unsegmented intermediate mesoderm developesthe excretory units of the urinary system.

Intermediate Mesoderm

Divisions of the lateral plate mesoderm:

Cavities form in the lat. Plate mesoderm that divide it up into 2 layers:

Somatic mesoderm: apposed to the ectoderm (forms CT and muscles and supportive elements of the body wall)

Splanchnic mesoderm: apposed to the endoderm (forms pleura, pericardium, peritoneum, smooth muscles, CV system)

Lateral Plate Mesoderm

At the beginning of 3rd week ectoderm is oval in shape

Ectoderm, over notochord and prechordal mesoderm, thickens to form neural palate(process is NEURULATION)

ORGANS DEVELOP FROMECTODERM

Process by which the neural tube is formed (future brain)

Neural tube is formed and closed by the end of week 4, there are openings cranially and caudally called neuropores.

Neural crest cells form as the neural tube closes

Neural crest cells form peripheral ganglia (sensory and autonomic and Schwann cells)

Neurulation Summary

Cells thicken in the ectoderm overlying the notochord (cranio-caudally)

Cells at the periphery of this edge form neural folds which elevate and fuse together in the middle forming a neural tube.

As it fuses some cells break away- neural crest cells. These cells migrate to the mesoderm along specific pathways to form peripheral ganglia.

The neuropores at either end must close, if the posterior one doesn’t close- SPINA BIFIDA. If the anterior one doesn’t close- ANENCEPHALY.

More detail

Occulta Meningocoele Meningomyocoele

Folic Acid important in preventing this. Unknown mechanism of action but thought to have an effect on cell division in the neural tube.

NEURAL TUBE DEFECTS

•During the 2nd month of development, the age of the embryo is then indicated as the crown-rump (CR) length and expressed in millimeters.

•Formation of the limbs, face, ears, nose, and eyes.•By the beginning of the 5th week, the hind and forefingers appear as paddle-shaped buds.

•Ossification in the long bones begin by the end of embryonic period (7th week).

EXTERNAL APPEARANCE DURING THESECOND MONTH

Describe the difference between the chorionic villi types?

What are the three layers of the trilaminar disc?

Describe the formation of the neural tube?

QUIZ

•Chromosomal abnormalities may be numerical or structural.

Chromosomal Abnormalities

Numerical Abnormalities •The normal human somatic cell contains

46 chromosomes. •The normal gamete contains 23.

Normal somatic cells are diploid, or 2n. Normal gametes are haploid.

Aneuploid refers to any chromosome number that is not euploid.

•it is usually applied when an extra chromosome is present (trisomy) or when one is missing (monosomy).

•Abnormalities in chromosome number may originate during meiotic or mitotic divisions.

Sometimes, however, separation does not occur (nondisjunction), and both members of a pair move into one cell.

•As a result of nondisjunction of the chromosomes, one cell receives 24 chromosomes, and the other receives 22 instead of the normal 23.

When, at fertilization, a gamete having 23 chromosomes fuses with a gamete having 24 or 22 chromosomes, the result is an individual with either 47 chromosomes (trisomy) or 45 chromosomes (monosomy).

•Nondisjunction, which occurs during either the first or the second meiotic division of the germ cells, may involve the autosomes or sex chromosomes.

•In women, the incidence of chromosomal abnormalities, including nondisjunction, increases with age, especially at 35 years and older.

Occasionally nondisjunction occurs during mitosis (mitotic nondisjunction) in an embryonic cell during the earliest cell divisions.

•Such conditions produce mosaicism, with some cells having an abnormal chromosome number and others being normal.

•Affected individuals may exhibit few or many of the characteristics of a particular syndrome, depending on the number of cells involved and their distribution.

Sometimes chromosomes break, and pieces of one chromosome attach to another.

•Such translocations may be balanced, in which case breakage and reunion occur between two chromosomes but no critical genetic material is lost and individuals are normal.

•Or they may be unbalanced, in which case part of one chromosome is lost and an altered phenotype is produced.

For example, unbalanced translocations between the long arms of chromosomes 14 and 21 during meiosis I or II produce gametes with an extra copy of chromosome 21, one of the causes of Down syndrome.

•Translocations are particularly common between chromosomes 13, 14, 15, 21, and 22 because they cluster during meiosis.

•Down syndrome is usually caused by an extra copy of chromosome 21 (trisomy 21).

•Features of children with Down syndrome include growth retardation, varying degrees of mental retardation, craniofacial abnormalities, including upward slanting eyes, epicanthal folds, flat facies, and small ears, cardiac defects, and hypotonia.

•These individuals also have relatively high incidences of leukemia, infections, thyroid dysfunction, and premature aging.

•Furthermore, nearly all develop signs of Alzheimer’s disease after age 35.

TRISOMY 21 (DOWN SYNDROME)

In 95% of cases, the syndrome is caused by trisomy 21 resulting from meiotic nondisjunction, and in 75% of these instances, nondisjunction occurs during oocyte formation.

•The incidence of Down syndrome is approximately 1 in 2000 conceptuses for women under age 25.

•This risk increases with maternal age to 1 in 300 at age 35 and 1 in 100 at age 40.

In approximately 4% of cases of Down syndrome, there is an unbalanced translocation between chromosome 21 and chromosome 13, 14, or 15.

•The final 1% are caused by mosaicism resulting from mitotic nondisjunction.

•These individuals have some cells with a normal chromosome number and some that are aneuploid.

•They may exhibit few or many of the characteristics of Down syndrome.

•Patients with trisomy 18 show the following features: mental retardation, congenital heart defects, low-set ears, and flexion of fingers and hands.

•In addition, patients frequently show micrognathia, renal anomalies, syndactyly, and malformations of the skeletal system.

•The incidence of this condition is approximately 1 in 5000 newborns.

•Eighty-five percent are lost between 10 weeks of gestation and term, whereas those born alive usually die by age 2 months.

TRISOMY 18

•The main abnormalities of trisomy 13 are mental retardation, holoprosencephaly, congenital heart defects, deafness, cleft lip and palate, and eye defects, such as microphthalmia, anophthalmia, and coloboma.

•The incidence of this abnormality is approximately 1 in 20,000 live births, and over 90% of the infants die in the first month after birth.

TRISOMY 13

•The clinical features of Klinefelter syndrome, found only in males and usually detected at puberty, are sterility, testicular atrophy, hyalinization of the seminiferous tubules, and usually gynecomastia.

•The cells have 47 chromosomes with a sex chromosomal complement of the XXY type, and a sex chromatin body (Barr body) is found in 80% of cases.

KLINEFELTER SYNDROME

The incidence is approximately 1 in 500 males. •Nondisjunction of the XX homologues is the

most common causative event. •Occasionally, patients with Klinefelter

syndrome have 48 chromosomes: 44 autosomes and four sex chromosomes (XXXY).

•Although mental retardation is not generally part of the syndrome, the more X chromosomes there are, the more likely there will be some degree of mental impairment.

•Turner syndrome, with a 45,X karyotype, is the only monosomy compatible with life. Although, 98% of all fetuses with the syndrome are spontaneously aborted.

•The survivals are female in appearance and are characterized by the absence of ovaries (gonadal dysgenesis) and short stature.

•Other common associated abnormalities are webbed neck, lymphedema of the extremities, skeletal deformities, and a broad chest with widely spaced nipples.

TURNER SYNDROME

Approximately 55% of affected women are monosomic for the X and chromatin body negative because of nondisjunction.

•In 80% of these women, nondisjunction in the male gamete is the cause.

•In the remainder of women, structural abnormalities of the X chromosome or mitotic nondisjunction resulting in mosaicism are the cause.

Structural Abnormalities •They involve one or more chromosomes,

usually result from chromosome breakage. •Breaks are caused by environmental factors,

such as viruses, radiation, and drugs. •The result of breakage depends on what

happens to the broken pieces. •In some cases, the broken piece of a

chromosome is lost, and the infant with partial deletion of a chromosome is abnormal.

A well-known syndrome, caused by partial deletion of the short arm of chromosome 5, is the cri-du-chat syndrome.

•Such children have a catlike cry, microcephaly, mental retardation, and congenital heart disease.

•Many other relatively rare syndromes are known to result from a partial chromosome loss.

•Microdeletions, spanning only a few contiguous genes, may result in microdeletion syndrome or contiguous gene syndrome.

•An example of a microdeletion occurs on the long arm of chromosome 15.

•Inheriting the deletion on the maternal chromosome results in Angelman syndrome.