Lectures of Human Embryology

By

DR. ABDEL-MONEM AWAD HEGAZY M.B. with honor 1983,

Dipl."Gynecology and Obstetrics "1989,

Master "Anatomy and Embryology" 1994,

M.D. "Anatomy and Embryology" 1999

Associate Professor of Anatomy and Embryology Faculty of Medicine, Zagazig University (Egypt) &

College of Medicine, Majmaah University (Saudi Arabia)

Fertilization

Definition:

It is the union of a sperm with a mature ovum to form

fertilized ovum (called zygote).

Site:

Fertilization occurs in the lateral third of the uterine tube (in

the ampulla). N.B.: The ovum (or 2ry oocyte) is viable for 24 hours after its release from the ovary

(ovulation), while the sperm retains its fertilizing power within the female genital

tract for about 48 hours. Therefore, for occurrence of fertilization, sexual intercourse

must occur not more than 48 hours before ovulation and not more than 24 hours after

ovulation. The oocyte reaches the site of fertilization by contraction and movement of

cilia of the uterine tube while the sperms that are motile cells reach this site through

propelling movements of their tails (the trip of sperms to reach the site of fertilization

is about 5-7 hours).

Site of Fertilization in Uterine Tube and Ovulation

Process of Fertilization

It occurs as follows:-

1. Several sperms reach the 2ry oocyte and surround it.

2. Only one sperm penetrates the oocyte (the other sperms

are prevented from entering it).

N.B.: Acrosome reaction: It is the reaction occurring

when the sperm becomes in contact with zona pellucida to

facilitate its penetration. This results in release of contents

of acrosome including enzymes needed for penetration,

e.g. acrosin- and trypsin-like substances.

3. Immediately after entry of the sperm, the 2ry oocyte

divides by the 2nd

meiosis to give the ovum and small 2nd

polar body (that degenerates).

4. The nucleus of the entering sperm loosens to form the

male pronucleus.

5. The nucleus of the ovum loosens to form the female

pronucleus.

6. Then the 2 pronuclei fuse to form a single nucleus,

forming zygote.

Diagrams showing the Process of Fertilization

Results:

1. Restoration of the diploid number of chromosomes (46).

2. Initiation of cleavage (or cell division), to form the fetus.

3. Specious variation, i.e. the new man is different from other

population, even from his mother and father, because he

represents a new mixture of chromosomes (one half form

the mother and the other half from the father).

4. Sex determination; as follows:

If the sperm carries Y-chromosome, the fetus will be

male.

If the sperm carries X-chromosome, the fetus will be

female.

Twins

Definition: One fertilization results in more than one foetus.

Types:

There are two types; uniovular and binovular twins.

Uniovular (monozygotic)

twins

Binovular (dizygotic) twins

-It results from fertilization of

one ovum by one sperm

(Splitting the zygote at

different stages of

development).

-They have one (or single)

placenta.

-They are of the same sex and

characters (identical twins). N.B.: If splitting occurs early in development "at

the two-cell stage", each embryo will has its own

placenta, amniotic cavity and chorionic cavity.

This case resembles that of dizygotic twins.

-It results from fertilization of

2 ova by 2 sperms.

- They have two separate

placentae.

-They are of the same or

different sex, but the

characters are not identical.

Opened Pregnant Uterus, showing Identical Twins

N.B.: Conjoined twins occur as a result of partial splitting of

the developing embryo at later stages of development (at the

stage of primitive node and streak)

Opened Pregnant Uterus, showing Full-Term Fetus

Early Stages of Embryonic Development

The human development is a complex process. It starts with a

single cell (fertilized ovum) and ends with an extremely

complex human being consisting of trillions of cells.

In this subject, the only first major events will be mentioned.

1. Cleavage

The fertilized ovum (zygote) begins to divide by mitotic

cell divisions, forming; firstly 2 cells then 4 cells, and so

on to reach a mass of cells formed of 32 cells, called

morula. The developing embryo passes to the uterine

cavity, whilst cell divisions occur. (It reaches the uterine

cavity, about 3 days after fertilization).

2. Blastocyst

The mass of cells (morula) on reaching the cavity of

uterus, it begins to absorb some fluids from this cavity.

The fluid collects in-between the cells, dividing them into

2 groups of cells; outer cells surrounding the developing

embryo called trophoblast and an inner cell mass,

displaced to one side called embryoblast. The developing

embryo is then called blastocyst. (tropho= nourishing,

blast = primitive cells).

Early stages of cleavage development

Implantation

Site: -It occurs in the endometrium of the body of uterus

(superior, posterior part),

Time -It occurs at about the 7th

day after ovulation.

-The blastocyst erodes the thick endometrium. Then, it

becomes completely hidden inside it (by about the 12-14th

day after ovulation i.e. the day of the expected next

menses to start).

Process:

a. The blastocyst increases in size, due collection of

more fluid from the uterine cavity.

b. This size increase leads to rupture and disappearance

of the zona pellucida.

c. This leads to direct contact of the trophoblast

covering the inner cell mass (which is sticky) with

the endometrium.

d. Attachment to the endometrium causes the cells of

trophoblast to divide repeatedly forming 2 layers;

inner called: cytotrophobalst and outer layer of cells

without cell boundaries called: syncytiotrophoblast.

e. Syncytiotrophoblast erodes the endometrium.

f. As the blastocyst sinks into the endomerium, it

becomes completely surrounded by 2 layers

(cytotrophobalst and syncytiotrophoblast).

g. After completion of implantation, the site of

penetration is closed by fibrin clot that is replaced by

epithelium, hence the endometrium becomes

continuous.

N.B.: The placenta is formed at the site of implantation

and formed by two components; maternal part

(endometrial part) and fetal part (trophoblastic part).

Site of Implantation in Endometrial lining of Uterine body

2ND

WEEK

I. Development of bilaminar embryonic disc:

- The cells of the inner cell mass (embryoblast)

differentiate into 2 layers:

1. Epiblast layer (ectoderm): tall columnar cells-

dorsally (adjacent to trophoblast).

2. Hypoblast layer (endoderm): cuboidal or flattened

cells- ventrally (facing the blastocele).

Stage of bilaminar embryonic disc

II. Development of 2 new cavities within the

blastocyst:

A -Formation of amniotic cavity:

a. Small cavities appear dorsally between the

ectoderm and trophobalst.

b. Then these cavities fuse together forming a

single amniotic cavity.

c. The cavity is then roofed by a layer of cells,

called amnioblastic cells, derived from the

epiblast cells adjacent to trophoblast.

B -Formation of yolk sac:

a. Then, the blastocele changes into the

primary yolk sac, through the appearance of

flattened layer of cells its floor, called

Hauser membrane, (probably derived from

the cytotrophoblast).

b. Then, the primary yolk sac changes into

secondary yolk sac, through the appearance

of another flattened layer of cells, derived

from the endoderm. Then the new small

cavity is pinched off from the 1ry yolk sac. It

is completely surrounded by endoderm. This

occurs about at the day 12.

Development of amniotic cavity and secondary yolk sac

Development of amniotic cavity, secondary yolk sac, exocoelomic cyst and chorionic

villi

III. Development of extra-embryonic mesoderm and

coelom:

A. Loose cellular tissue detach from the inner

layer of cytotrophoblat. It proliferates and fills the

space between trophoblast externally and the

amnion and yolk sac internally, forming

"extraembryonic mesoderm" (EEM).

B. Then the intercellular spaces coalesce to form a

single cavity called extraembryonic coelom (EEC). This cavity enlarges to surround the amnion and primary

yolk sac, except at the part connecting the embryonic

disc with trophoblast called connecting stalk.

The EEM linning the trophoblast and covering the

amnion is called somatic or parietal layer of EEM, while

that covering the the yolk sac is known as viscral layer of

EEM.

Development of extra-embryonic mesoderm and coelom

3RD

WEEK

(Gastrulation) or

(Development of Trilaminar Embryonic disc) The most charcteristics of the 3

rd week is the gastrulation (or formation of

trilaminar embryonic disc)

I. Development of primitive streak and primitive node:

- The ectodermal cells in the middle of cuadal half of the

embryonic disc proliferate and migrate between the cctoderm

and the endoderm, forming elnogated column of cells called

primitive streak.

- As the strak elongates caudally, its cranial end thickens to form

the primitive node (Hensen's node).

II. Development of notochord:

- The cells of the primitive node proliferate and migratecranially

between the ectoderm and endoderm till reaching the

prochordal plate, forming a mid-line cord called primitive

notochord or notochordal process.

- An invagination extends from the amion passing through the

primitive streak and then through the primitive notochord to

form the notochordal canal.

- The floor of the notochordal canal and the underlying endoderm

diaspprears resulting in a temporary connection between the

amiotic cavity and yolk sac called neurenteric canal.

- Later, the roof of the notochordal canal folds longitudinally and

proliferstes to form the definitive notochord.

- Soon afterwards, the continuity of the endoderm is restored and

the neurenteric canal is obliterated.

N.B.: Notochord is a solid cylinder of cells, extending from the

primitive streak to end at the prechordal plate.

Embryological importance of notochord:

1. It induces the differentiation of the overlying ectoderm

to form the neural plate.

2. It induces the formation of the vertebral column.

3. It forms the nucleus pulposus of the intervertbral discs.

N.B.: Over small areas; one at the cranial end and the other at the caudal

end of the germ disc, the ectoderm and endoderm are closely adherent.

The area at the cranial end is called prochordal plate and it later gives

rise to oropharyngeal membrane. On the other hand, the area at the caudal

end is called cloacal membrane.

Development of notochord

III. Development of 3rd

germ layer (intraembryonic mesoderm):

- The cells of th e primitive streak migrates laterally, forwards

and backwards to form a 3rd

layer of cells called

intraembryonic mesoderm (IEM). This layer occupies all the

space between the ectoderm and endoderm except 3 regions.

The regions do not occupied by intraembryonic mesoderm are:

1. Prochordal plate

2. Notochord

3. Cloacal membrane.

- The IEM differentiates into 3 longitudinal regions on each side

of the midline (or notochord and primitive streak):

1. Medial mesoderm called Paraxial mesoderm: It

becomes organized into segments called somites.

2. Intermediate mesoderm: It forms the dorsal longitudinal

ridge called urogenital ridge that gives rise the future

kidneys and gonads.

3. Lateral plate mesoderm into which the intraembryonic

coelom develops.

Development of intra-embryonic mesoderm

Differentiation of intra-embryonic mesoderm

IV. Development of the intraembryonic coelom (IEC)

- A single U-shaped cavity called intraembryonic coelom

develops in the lateral plate mesoderm and infront of the

prochordal plate.

- It divides the mesoderm into 2 layers:

1. Dorsal layer called somatic (parietal) layer. It gives rise to

the parietal layer of the serous membranes (pleura,

pericrdium and peritoneum).

2. Ventral layer called splanchnic (visceral) layer. It gives rise

to the visceral layer of the serous membranes (pleura,

pericrdium and peritoneum).

- Fate of IEC:

During the 2nd

month the IEC is divided as follows:

1. The cranial transverse part (infront of prochordal plate)

gives rise to the pericardium.

2. The cranial part of the lonitudinal limb gives rise to

pleura.

3. The caudal part of the lonitudinal limb gives rise to

peritonium.

Derivatives of intra-embryonic mesoderm

V. Development of Somites - By the end of the 3

rd week (about at the 20

th day), the paraxial

mesoderm starts to be divided into blocks of cells called

somites.

- The 1st pair of somites appear just caudal to the cranial end of

the notochord.

- Then new somites appear in a cranio-caudal sequence, nearly 3

pairs of somites per day.

- About 30 pairs of somites appear during the so-called somite

period (day 20 to day 30). During this period the age of the

embryo can be roughly estimated from the somites.

- Total 42-44 pairs are formed by the end othe 5th week, as

follows:-

4 pairs –occipital

8 pairs – cervical

12 pairs – thoracic

5 pairs – lumbar

5 pairs – sacral

8-10 pairs – coccygeal.

- Fate (derivatives) of somites:

1. The first occipital and last 5-6 coccygeal pairs disappear

2. Each of the remaining somites divides into 3 parts:

Dorsolateral part called dermatome. It gives rise to the

dermis and subcutaneous tissue of skin.

Intermediate part called myotome. It gives rise to

skeletal muscles of tongue, thorax, abdomen and

prabably limbs.

Ventromedial part called sclerotome. It gives rise to

bones, cartilages and ligaments of vertebral column and

ribs.

VI. Folding of the Embryo

- It begins by the end of the 3rd

week and becomes complete

during the 4th week.

- The folding is due to rapid development of the central part of

the embryo, especially the central nervous system than the

peripheral part, as well as the more expansion of the amniotic

cavity.

Types of foldings

1. Craniocaudal foldings:

a. Crainal (Head) fold: The cranial end (the

or0pharyngeal membrane, cardiogenic area and

transverse septum) of the embryonic disc folds

ventrally.

b. Caudal (Tail) fold: The caudal end (cloacal

membrane and connecting stalk) of the embryonic disc

folds ventrally.

2. Lateral folds (2): The right and left sides of of the

embryonic disc, containing the longitudinal limbs of

intraembryonic coelom folds ventrally.

Then the 4 folds meet ventral to the embryo.

Results of folding:

1. Result of 4 foldings:

- The embryo becomes cylindrical in shape.

- A ring called primitive umbilical ring develops

ventral to the embryo.

- Part of yolk sac is incorporated within the embryo

forming the gut.

N.B.: The part of gut incorporated in the head fold is

called foregut, part in the tail fold called hindgut

and the part inbetween (connected to the definitive

yolk sac through the umbilical ring is the midgut.)

2. Result of cranial folding:

- The forebrain grows dorsal to the oropharyngeal

membrane.

- The cardiogenic area and the septum transversum

becomes ventral in postion.

3. Result of caudal folding:

- The cloacal membrane becomes the most caudal part.

- The connecting stalk becomes ventral to the embryo.

4. Result of lateral foldings:

- The caudal parts of the longitudinal limbs of IEC fuse

together forming the pertioneal cavity.

- The intermediate mesoderm forming the urogenital

system becomes dorsal in postion.

Folding of embryo

N.B.: Trnsverse septum is the mesoderm connecting the

the amion and yolk sac cranially.

Opened Pregnant Uterus, showing Embryonic Development

Clinical Correlations

Implantation in the lower part of the uterus results in a condition called

placenta previa, that commonly results in bleeding before delivery. It

includes:

placenta previa lateralis, the placenta is low in position, but it

does not reach the margin of the cervix.

placenta previa marginalis; the placenta reaches the margin of

the cervix.

placenta previa centralis; the placenta reaches the center of the

cervix. This last case usually needs surgical abdominal delivery

(caesarian section).

Abnormal sites of implantation (sites of ectopic pregnancy)

include the following sites:

The uterine tube (represents about 95% of cases of ectopic

pregnancy, mostly in the ampulla of the tube),

The ovary,

The abdominal (peritoneal) cavity: In this case, it may implant

in any site covered by peritoneum. However, it mostly implant

in Douglas (recto-uterine) pouch. N.B.: Cases of ectopic pregnancy mostly die about the 2

nd month pregnancy, causing

internal hemorrhage and severe lower abdominal pain.

Hydatidiform (vesicular) mole: The uterus is distended by thin walled,

translucent, grape-like vesicles of different sizes. This case is caused due

to excessive proliferation of the trophoblast. In this condition, there is

excessive secretion of gonadotrophins. It may change into malignant

tumour called chorion epithelioma.