HUMAN EMBRYOLOGY

Puspita K Dewi, MD
Biology Department
Faculty of Medicine Diponegoro University

DEFINITION

embryo & logos

Embryo- 1st stages of development of an
organism after the zygote forms
Logos - knowledge
The branch of biology that deals with the
formation, structure, early growth, and
development of living organisms.

WHY STUDY HUMAN

EMBRYOLOGY ?

Best way to understand and remember

human anatomy
Benefit you more and more as you continue
your studies in next steps
Bridge your basic science and clinical science
courses, especially obstetrics and pediatrics

Embriology
is FUN

PERIOD OF HUMAN
EMBRYOLOGY

Period of egg
from fertilization to the end of 3rd week
Period of embryo
beginning of 4th week to the end of 8th week
Period of fetus
from the beginning of 3rd month to birth

FERTILIZATION (3 STEPS)
1.Contact and recognition (Casual
Introductions)

Sperm undergo capacitation (further

maturation) within the female reproductive
tract
Sperm reach the egg in the oviduct where
fertilization will occur

2.Sperm Entry

Only ONE sperm is allowed to enter

Fast block - electrical charge in egg plasma
membrane prevents polyspermy
Slow block - depolarization of egg plasma
membrane due to Ca++ release
1st phase : Penetration of corona radiata
2nd phase : Penetration of zona pellucida

Sperm undergo acrosome reaction, occurs

after binding to the zona pellucida, is
induced by zona proteins. This reaction
culminates in the release of hydrolic
enzymes needed to penetrate the zona
pellucida

3.Fusion (3rd phase)

The sperm nucleus is propelled to the egg
nucleus by microtubules

SPERM made of 3 parts

head- contains haploid

nucleus & acrosome
(enzymes that allow
sperm to penetrate the
egg)
middle piece- contains
mitochondria (make
energy; ATP)
tail- flagellum- allows
sperm to swim toward
the
egg

EGG CELL

1ST PHASE : PENETRATION OF

CORONA RADIATA

Consist of folicular ephitelial cells

Only capacitated sperm pass freely through
corona cells

2ND PHASE : PENETRATION OF

ZONA PELLUCIDA

ligand ZP3, a zona protein, facilitates and

maintains sperm binding and induces the
acrosome reaction
release of hydrolic enzymes needed to
penetrate the zona pellucida

13

3RD PHASE :FUSION OF OOCYTE

AND SPERM CELL MEMBRANES

plasma membranes of the sperm and egg

fuse
both the head and tail of the spermatozoon
enter the cytoplasm of the oocyte, but the
plasma membrane is left behind on the
oocyte surface
Cortical and zona reactions (prevent
polyspermia)
Resumption of the second meiotic division
Metabolic activation of the egg

JOINING OF MALE AND FEMALE

PRONUCLEUS MITOTIC DIVISIONS

see video
This is cleavage

..FIRST WEEK..

1st STADIUM
two-cell stage (approximately 30 hours of
age)
2nd STADIUM
morula containing 12 to 16 blastomeres
(approximately 3 days of age)
Asinkrone divisions : 3, 12, 20 blastomeres
advanced morula stage reaching the uterine
lumen (approximately 4 days of age)
Migration of human zygot toward uterus
facilitate by tuba contraction and cilia

LET THE DIVISION BEGIN!

3rd STADIUM
early blastocyst stage (approximately 4.5
days of age; the zona pellucida has
disappeared)
early phase of implantation (blastocyst
approximately 6 days of age). six days for
ovulasi implantasi phase
Free blastocyst (cavity begins to appear)
OUTER CELL MASS (TROFOBLAS)
INNER CELL MASS (EMBRIOBLAS)
BLASTOCYST CAVITY
Diameter : 0,25 mm

4th STADIUM
IMPLANTATON
The uterus at the time of implantation is in
the secretory phase, and the blastocyst
implants in the endometrium along the
anterior or posterior wall
Trofoblas cell SINSISIUM implants in the
endometrium
Embrioblas cell anterior wall

..SECOND WEEK..

Uteroplacenta circulation
Early phase of implantation :
kolaps of blastocist and deep implant of
trofoblast
invasif implantation reach stratum compactum
endometrii
differentiate to decidua cell
Late phase :
ekspansion of blastocyst, developed
decidual reaction : change of endometrial
along implantation phase. Cells of the
endometrium, meanwhile, become polyhedral and
loaded with glycogen and lipids; intercellular
spaces are filled with extravasate, and the tissue
is edematous

WEEK OF TWOS

Trofoblas
(a) Cytotrophoblast, an inner, actively
proliferating layer
(b) Syncytiotrophoblast, an outer layer which
erodes maternal tissues
Embrioblast
(a) Epiblast and (b) the Hypoblast, together
forming a bilaminar disc
Two cavities formed
the amniotic and yolk sac cavities

Amnion is an ectoderm structure derived

from embrioblas
Primitive yolc sac are formed inside the
blatocist cavity

UTEROPLACENTAL CIRCULATION

By day 9
lacunae develop in the syncytiotrophoblast.
Subsequently, maternal sinusoids are eroded
by the syncytiotrophoblast, maternal blood
enters the lacunar network
by the end of the second week, a primitive
uteroplacental circulation begins

..THIRD WEEK..

GASTRULATION

Formation of Embryonic Ectoderm, Mesoderm

and Endoderm
Mesoderm and endoderm cell layers derived
from epiblast cells which move inward
(invaginate)
Epiblast cells which remain form ectodermal
cell layer
these layers form all of the tissues and
organs

Gastrulation begins with formation of the

Primitive streak on the surface of the epiblast
Cephalic end of primitive streak primitive
pit and primitive node
Invagination : migration of epiblast cells
toward primitive streak controlled by FGF8
(fibroblast growth factor 8)
Once the cells have invaginated, some
displace the hypoblast, creating the
embryonic Endoderm, and others come to lie
between the epiblast and newly created
endoderm to form Mesoderm. Cells remaining
in the epiblast then form Ectoderm

Establishment of the Body Axes

Establishment of the body axes,

anteroposterior, dorsoventral, and leftright,
takes place before and during the period of
gastrulation
Notochord forms a midline axis, which will
serve as the basis of the axial skeleton
Genes regulate dorsoventral axis :
OTX2, LIM1, HESX1, TGF, Brachyury (T)
Genes regulate left-right axis :
FGF8, Nodal and Lefty-2, PITX2

By the end of the third week, three basic

Germ layers, consisting of ectoderm,
mesoderm, and Endoderm, are established in
the head region, and the process continues
to produce these germ layers for more
caudal areas of the embryo until the end of
the fourth week.
Tissue and organ differentiation has begun,
and it occurs in a cephalocaudal direction as
gastrulation continues.

Further development of trophoblast

In the meantime, the trophoblast progresses

rapidly. Primary villi obtain a mesenchymal
core in which small capillaries arise
When these villous capillaries make contact
with capillaries in the chorionic plate and
connecting stalk, the villous system is ready
to supply the embryo with its nutrients and
oxygen

..THIRD TO EIGHT WEEK..

Embrionic periode

three germ layers gives rise to its own tissues

and organ systems
ectodermal germ layer gives rise to the
organs and structures that maintain contact
with the outside world:
(a) central nervous system
(b) peripheral nervous system
(c) sensory epithelium of ear, nose, and eye
(d) skin, including hair and nails
(e) pituitary, mammary, and sweat glands
and enamel of the teeth

mesoderm forms Somites give rise to

(a) myotome (muscle tissue)
(b) Sclerotome (cartilage and bone)
(c) Dermatome (subcutaneous tissue of the
skin)
which are all supporting tissues of the body
(d) vascular system, i.e., the heart, arteries,
veins, lymph vessels, and all blood and lymph
cells
(e) urogenital system: kidneys, gonads, and
their ducts (but not the bladder)
(f) spleen and cortex of the suprarenal
glands

endodermal germ layer provides

the epithelial lining of
(a) gastrointestinal tract
(b)respiratory tract
(c) urinary bladder.
Parenchyma of the
(d) thyroid
(e) parathyroids,
(f) liver
(g)pancreas
the epithelial lining of
(h) tympanic cavity and auditory tube

(A)

(B)

HOMEOBOX GENES

HOXA, HOXB, HOXC, and HOXD, on four

different chromosomes
code for transcription factors that activate
cascades of genes regulating phenomena
such as segmentation and axis formation
Genes toward the 3 end of the chromosome
control development of more cranial
structures; those more toward the 5 end
regulate differentiation of more posterior
structures.
Together,
they
regulate
patterning of the hindbrain and axis of the
embryo

Sex differentiation

HUMAN SEXUAL
DIFFERENTIATION
Tjio and Levan (1956) discovered 46 diploid
for humans; 22 pairs of autosomal
chromosomes and 1 pair of sex chromosomes

SEXUAL DIFFERENTIATION IN
HUMANS
1.
2.
3.
4.
5.

All human embryos undergo a

hermaphroditic period
5th week of gestation, gonadal primordial
arise
Primordial germ cells become cortex/inner
medulla
Cortex develop into ovary
Medulla develop into testis

6.

7.

8.
9.

7th week of gestation, if XY

chromosomes are present, medulla
develops into testis. If no Y present,
cortex forms ovarian tissue
Initiation of testis stimulates production
of two hormones that is needed for
male sex differentiation
Males produce spermatocytes at
puberty
Females arrest eggs in meiosis by 25th
week

WHAT MAKES US MALE OR FEMALE?

Chromosomic Sex
Gonadal Sex
Genital Sex
Brain Differentiation

CRITICAL WINDOW OF SUSCEPTIBILITY:

MALE OR FEMALE?
PregnancyWeek

Sexuallyindifferentfetus
Testisformation
hormones

78
Development

islargelyhormone
independent

~15

Windowof
hormone
susceptibility

Developmentis
TOTALLY
Hormonedependent

Gonads and internal genitalia

SRYgene
Development of testes

Mullerian Inhibiting
Factor & others

Testosterone
Mllerian Duct degenerates

Wollfian duct develops

Epididymis
Vas Deferens
Seminal Vesicles
Prostate Gland

Male Differentiation
Testosterone(fromtestes)
Wolffian Duct develops

Epididymis
VasDeferens
SeminalVesicles
ProstateGland

MALE DIFFERENTIATION
SRYgene

MullerianInhibitingFactor&otherfactors
Mllerian Duct degenerates

MALE FETUS

TDF
Results in degeneration of gonadal cortex
and differentiation of the medullary
region of the gonad into Sertoli cells
Sertoli cells
Secrete glycoprotein known as antimullerian hormone(AMH)
Cause regression of paramesonephric
duct system in male embryo
Signal for differentiation of Leydig cells
from the surrounding mesenchyme

MALE FETUS

Leydig cells
Produce

testosterone,dihydrotestosterone with 5areductase

Testosterone
Responsible for evolution of mesonephric duct
system into vas deferens, epididymis, ejaculatory
ducts and seminal vesicle
At puberty, leads to spermatogenesis and changes
in primary and secondary sex characteristics
DHT
Results in development of the male external
genitalia and prostate and bulbourethral glands

FEMALE DIFFERENTIATION
No Y, No
SRY, No MIF

Wnt-4 Gene
Activates Mllerian Duct

Fallopian Tubes
Uterus
Cervix
Inner vagina

Development
of ovaries

WNT-4 GENE

Essential for female development

Prevents production of testosterone
Initiates development of Mullerian
duct
Necessary for proper oocyte
development
Suppresses Wolffian duct

FEMALE FETUS

In the absence of TDF, medulla regresses and

cortical sex cords break up into isolated cell
clusters(primordial follicles)

in the absence of AMH & testosterone,

Mesonephric duct system degenerates
Then, paramesonephric duct system develops
Inf. fused portion
Uterovaginal canal -> uterus and upper vagina
Cranial unfused portions
Open into celomic cavity(future peritoneal
cavity)
Fallopian tubes

GENITAL SEX

GENITAL SEX

BRAIN DIFFERENTIATION

Presence of androgens Brain Male

Absence of androgens - Brain Female

BRAIN DIFFERENTIATION

In the presence of SRY Testes

In the absence of SRY Ovary like

Two doses of DSS needed to develop fully

functioning ovaries.

BRAIN SEXUAL CHEMISTRY

BRAIN DIFFERENTIATION RATS

..thank
you..