EMBRIOGENESIS

Dr. Zainuri Sabta N

Departemen Anatomi FK UII
Introduksi
Lingkup Bahasan Embriologi
Gametogenesis
Fertilisasi
Implantasi
Embryogenesis
Organogenesis

2
Gametogenesis
Gametes (oocytes and spermatozoa) are the descendants of
primordial germ cells that originate in the wall of the yolk sac
in the embryo and migrate to the gonadal region.
Gametogenesis
Male Gametogenesis (Spermatogenesis)

Spermatogenesis = cell division
and shape changes
Spermiogenesis - shape changes
and acrosome formation

In males, gametogenesis begins at
puberty and continues into advanced
age. Primordial germ cells (46,2N)
migrate into the testes at week 4 of
development and remain dormant. At
puberty, primordial germ cells
differentiate into type A
spermatogonia (46,2N). Type A
spermatogonia divide by mitosis to
form either more type A
spermatogonia (to maintain the
supply) or type B spermatogonia.
Sertoli cells = nurse cells.
Interstitial cells of Leydig = testosterone
Female Gametogenesis (Oogenesis)
In females, most of gametogenesis
occurs during embryonic development.
The numbers of human oocyte
At 5 months gestation 7 millions
At birth 1 million
Puberty 40.000
Of the 40.000 oocytes remaining at
puberty only about 400 undergo
ovulation during the reproductive years

Female Gametogenesis (Oogenesis)
Primordial germ cells migrate
into the ovaries at week 4 of
development and differentiate
into oogonia (46,2N). Oogonia
enter meiosis I and undergo
DNA replication to form
primary oocytes (2N,4C).
All primary oocytes are formed
by the fifth month of fetal life
and remain dormant in
prophase of meiosis I until
puberty.
Female Gametogenesis
Primary follicle, secondary or
antral follicle, preovulatory
Mature ovum is surrounded by
zona pellucida and corona
radiata, inside Graafian follicle
just before follicle ruptures
Follicle remnant becomes
corpus luteum, which have
granulosa cells and theca
interna = progesterone
If fertilization occurs, then the
corpus luteum is maintained
by human chorionic
gonadotropin (hCG) produced
by the syncytiotrophoblast =
forms basis for a pregnancy
test.
Eventually corpus luteum
degenerates into corpus
albicans




During a womans ovarian cycle one oocyte is
selected to complete meiosis I to form a secondary
oocyte (1N,2C) and a first polar body. After
ovulation the oocyte is arrested in metaphase of
meiosis II until fertilization. At fertilization, the
secondary oocyte completes meiosis II to form a
mature oocyte (23,1N) and a second polar body
Transport of Sperm in Female
Sperm are deposited in the upper vagina and must
overcome several obstacles to reach an egg in the
ampulla of one of the uterine tubes.
Sperm undergo final maturation (capacitation) within
the female reproductive tract; the acrosome contains
enzymes to digest the membrane of the ovum
Sperm lose their ability to fertilize an egg after 3 - 3
days. The egg itself is viable for only about 24 hours.
Approximation: Only a tiny fraction of sperm actually
reaches the ampulla of the uterine tube to be near the
egg.
Table 1 - Obstacles to Sperm Transport
Obstacle Adaptation
Low pH of upper vagina The alkaline seminal fluid temporarily neutralizes the
normal acidity (pH 4.3 pH 7 7.2) to allow the sperm to
survive in the upper vagina.
Cervical mucus The composition of cervical mucus changes during
menstrual cycle. Sperm can most easily penetrate the
thinner E-mucus that predominates during the last few days
before ovulation, as opposed to the thicker G-mucus.
Cervical canal, uterus Two modes of transport:
Rapid some sperm travel from the vagina to the upper 1/3
of the uterine tube in as little as 30 minutes. Since sperm
normally swim only 2-3 mm/hr, it is thought that they are
actively transported by smooth muscle contractions of the
female or some other mechanism.
Slow the rest of the sperm swim their way up the last part
of the cervical tube, are stored in cervical crypts (folds of the
cervix), and are slowly released into the uterus over 2-3
days.
TAHAPAN PERKEMBANGAN EMBRIO-JANIN
(berdasarkan urutan waktu)
Week 1
Day 1: Fertilisasi, pembentukan zygote di dalam tuba
Day 2: pembelahan (Cleavages ) membentuk blastomer
Day 3: Morula forms ICM and trophoblast
Day 4: Blastocoel is formed, zona pellucida breaks down
Day 5/6: Implantation into uterine wall

TAHAPAN PERKEMBANGAN EMBRIO-JANIN
(berdasarkan urutan waktu)
Week 2
Trophoblast connects with maternal circulation
Bilaminar germ disc forms (epiblast and hypoblast)
Amniotic cavity forms

Week 3
Gastrulation: primitive streak and node, formation of
ectoderm, mesoderm and endoderm
Notochord forms from notochordal plate
Cloacal membrane and allantois form
Development in a cranial to caudal direction


TAHAPAN PERKEMBANGAN EMBRIO-JANIN
(berdasarkan urutan waktu)
Week 4
Neurulation: neural plate, neural folds, neural plates; proceeds
middle to ends
Neural crest cells form
Paraxial, intermediate, and lateral plate mesoderm can be
distinguished
Paraxial mesoderm forms somites, cranial to caudal direction;
somites differentiate into dermo-, myo-, and sclerotome parts
Intermediate mesoderm begins to form mesonephros (ginjal)
Lateral plate mesoderm gives rise to somatic and splanchnic
mesoderm, intraembryonic coelom forms
Folding laterally and craniocaudally, which is also important to GI
development
Through Week 8, embryogenesis of all major organ systems


TAHAPAN PERKEMBANGAN EMBRIO-JANIN
(berdasarkan urutan waktu)
Week 9 to birth
Fetal development: overall growth, maturation of
tissues

Resumme
Week 1-2: formation of zygote, implantation and
formation of bilaminar embryo
Weeks 3-8: Embryological period
Weeks 9-38: Fetal period

Fertilization (first week)
Penetration of Zona Pellucida
Once the sperm has
penetrated the outer layers it
fuses with the plasma
membrane of the egg and
releases its contents inside.
The head and the tail of the
sperm degrade, so that all
mitochondria in the embryo
(and all mitochondrial DNA)
come from the mother.
Once inside the corona radiata, the sperm binds to the species-
specific ZP3 receptor on the eggs glycoprotein coat. This triggers
the acrosomal reaction, or the release of enzymes stored in the
sperms acrosome (e.g. acrosin). These enzymes help the sperm
drill through the zona pellucida
Fertilization (first week)
Cortical Reaction
Entry of a sperm into the egg triggers changes that prevent
polyspermy (fertilization of an egg by more than one sperm).
These changes are known as the cortical reaction.
Phase Description
Fast block Electrical depolarization of the eggs surface (70Mv
+10Mv) works for a short time to repel other sperm
electrostatically.
Slow block A wave of Ca
++
ions released from the point of sperm
entry spreads through the egg. This causes cortical
granules in the egg to release their contents.
Polysaccharides in the cortical granules reach the
outside of the egg and form a physical barrier to sperm
penetration. Enzymes in the granules break down the
ZP3 receptors in the zona pellucida and also further
harden the coat.
Table 4 - Cortical Reaction
Fertilization (first week)
Cortical Reaction
During ovulation oocyte
completes meiosis I, stops in
metaphase of meiosis II
Fusion of oocyte and sperm
membranes triggers -- oocyte
completes meiosis II
Afterwards the male and female
pronuclei fuse and the egg
completes its second meiotic
division, resulting in a second
polar body. The fertilized egg is
now known as the zygote
(together).
The 23 chromosomes of the
sperm join with the 23
chromosomes of the egg to
restore the diploidnumber of 46 in
the zygote.
A zygote has 22 pairs of
autosomes and one pair of sex
chromosomes; XX in females, XY
in males.

Fertilization (first week)
Fusion of Pronuclei
After fusion of pronuclei,
division of the blastomeres
forms a morula. Compaction is
followed by formation of the
blastocyst consisting of an inner
cell mass = embryo, and an
outer cell mass = trophoblast
(placenta).
The zygote undergoes a number of ordinary mitotic divisions that
increase the number of cells in the zygote but not its overall size. Within the
fallopian tube, the zygote begins mitotic divisions called cleavage to form
two-cell, four-cell, eight-cell stages, and so on. Each cycle of division takes
about 24 hours. The individual cells are known as blastomeres.

Cleavage (membelah)
Cleavage (membelah)
At the 32-cell stage the embryo is known as a morula (L.
mulberry), a solid ball consisting of an inner cell mass and
an outer cell mass. The inner cell mass will eventually
become the embryo and fetus, while the outer cell mass will
eventually become part of the placenta.
Blastocyst Formation
Compaction
The cells on the outside of the morula form tight
intercellular junctions and express ion channels
to create an impermeable barrier.
Cavitation
A fluid-filled cavity forms inside the morula.
This cavity is known as the blastocyst cavity or
blastocoele, and the morula is now called a
blastula or blastocyst. The inner cell mass is now
known as the embryoblast and the outer cell
mass becomes the trophoblast
Implantation
The zona pellucida must degenerate
for implantation to occur.
One function of the zona pellucida is
to prevent premature implantation.

Attachment and Invasion
The embryo attaches to and invades
into the maternal endometrium.
The trophoblast differentiates into
the cytotrophoblast and the
syncytiotrophoblast.
The embryo typically implants in the
posterior superior wall of the uterus.
The response of the maternal
endrometrial cells to the invading
embryo is called the decidual
reaction.
Implantation 5 to 8 days after fertilization


Implantasi lengkap
terjadi pada minggu
ke 14 kehamilan.
ECTOPIC TUBAL PREGNANCY


Jenis kehamilan ektopik ini apabila terjadi implantasi
blastocystr di lumen tubaoleh karena mengalami
keterlambatan transport
Lokasi paling sering ada di ampula dan excavatio
rectouetrina (cavum douglas)
Kehamilan ektopik sering terjadi pada wanita
denganendometriotis atau pelvic inflamatory disease
(PID)
Tuba mengalami ruptur dan perdarahan hebat yang
memungkinkan dilakukan salpingectomy

BAYI KEMBAR (TWIN)
Diagram bayi kembar A. dizigot B. monozigot C. conjoint twin (siam)


A. Dizigot (fraternal). Terjadi
bila 2 ovum dibuahi oleh
dua spermatozoa yang
berbeda.
B. Monozigot (identik). bila
terjadi fertilisasi antara 1
ovum dengan 1
spermatozoa, namun pada
saat zygot membentuk
blastocyst inner cell mass
(embrioblast) membelah
menjadi 2, sehingga identik.
C. Conjoined (siamese), terjadi
bila inner cell mass
(embrioblast) membelah
tidak lengkap/sempurna,
sehingga kedua bayi masih
terhubung oleh jaringan
(kepala, thorax atau pelvis)
IN VITRO FERTILISATION


Tahapan Bayi tabung
1. Ovarium distimulasi agar terjadi
multiple ovulation
2. Oocytes di ambil dengan aspirasi
jarum dengan dibantu USG
3. Spermatozoa diambil dengan
cara masturbasi dan dipisahkan
dari cairan semennya.
4. Spermatozoa dan oocytes
kemudian dikultur bersama.
Berhasil bila didapatkan dua
pronuclei dengan oocyte
(fetilisasi)
5. Dibiarkan terjadi cleavage secara
invitro menjadi 8 cel embrio
6. Kemudian diambil 3 embrio dan
dipindahkan ke dalam uterus
(kenapa3 embrio)?
7. Embrio sisanya di frozenkan
untuk dipakai kemudian bilamana
gagal terjadi kehamilan.

Embryo
weeks 1 through 8 of gestation
In the embryonic disc, three primary germ layers develop:
ectoderm, mesoderm, and endoderm.
By the eighth week of gestation (end of 2 months), all organ
systems are formed
Embryonic period is considered the most critical time in
human development for induction of birth defects. most
sensitive to teratogenic insult.
Fetus
weeks 9 through 40 of gestation
The organ systems grow and mature.
The growing fetus brings about structural and functional
changes in the mother


Uterus changes (first week)
Uterus: proliferative phase (estrogen), progestational
phase (progesterone, corpus luteum), menstrual phase
(basal layer of endometrium remains to regenerate.

Trophoblast secretes hCG = maintenance of corpus
luteum that makes progesterone to maintain
pregnancy.

No fertilization = no hCG = corpus luteum regresses =
no more progesterone = menstruation, leaving the
basal layer to regenerate endometrial glands for next
cycle.
Week 2:
Trophoblast consists of two layers = cytotrophoblast (makes cells),
syncytiotrophoblast = invasion and hormones.
Inner cell mass = germ disc = two layers: epiblast and hypoblast.
Two cavities: amniotic = dorsal to epiblast; yolk sac = ventral to
hypoblast.
Extraembryonic mesoderm formed around the amniotic and yolk
sac cavities = splits into two layers = somatic and splanchnic. Cavity
between = chorionic cavity.
Two layers of extraembryonic mesoderm connected at connecting
stalk (umbilical region).
At about 12-14 days, the embryo penetrates uterine vessels =
some bleeding = may misdiagnose as menstrual bleeding =
misdiagnose pregnancy and age of embryo.
Ectopic pregnancy = ampullary region = most common.
Rectouterine (Douglas) pouch = most common in abdomen.

Week 2 - week of 2s:
2 layers to trophoblast: syncytiotrophoblast and cytotrophoblast
2 layers to embryoblast: epiblast and hypoblast
2 cavities: amniotic and yolk sac
2 layers of extraembryonic mesoderm: somatic and splanchnic
Week 3:
Gastrulation = process of making three germ layers: ectoderm (skin,
CNS), mesoderm (blood, bones, connective tissue), and endoderm
(gut, parenchyma of glands).
Epiblast = forms all three germ layers = all of the embryo. Hypoblast
disappears.
Primitive streak forms at the caudal end of embryo at the beginning
of the third week = cell migration from epiblast to form germ layers.
Node = organizer = cranial end of streak = notochord cells.
Notochord = induces CNS, forms nucleus pulposus in intervertebral
discs.
Trophoblast = forms villi for placenta = vessels formed in
extraembryonic mesoderm connect to umbilical vessels = fetal
circulation
Week 3 = week of 3s:
3 germ layers: ectoderm, mesoderm, endoderm
3 cavities: amniotic, yolk sac, chorionic
Embryonic period (Week 3-8)
Ectoderm
Ectoderm: forms neural plate = induced by
organizer, notochord, and prechordal mesoderm
= block BMP-4 activity.
Neural plate folds into a tube = CNS.
Cells at top of neural folds = neural crest =
migrate to form bones and connective tissue of
the face and skull, spinal ganglia, sympathetic and
enteric ganglia, melanocytes, adrenal medulla,
cranial nerve ganglia (V, VII, IX, X).
Ectoderm
Mesoderm
paraxial (dorsal) = somites = vertebral
column. Somitomeres form in head
region and contribute to the base of
the skull
intermediate (ventral) = urogenital
structures
lateral plate (ventral) = splits into
splanchnic (visceral, surrounds
organs) and somatic (parietal, lines
body cavities)
Mesenchyme = any loose connective
tissue regardless of origin.
Mesoderm = derived from
mesodermal germ layer.
Somites = sclerotome (bone),
myotome (muscle), dermatome
(skin).
Sonic hedgehog from notochord and
floor plate of neural tube induces
sclerotome
Endoderma
Endoderm = gut tube and its
derivatives.
Cephalocaudal (head and tail
folds) and lateral folding closes
gut tube around the umbilical
region.
Vitelline duct (yolk sac duct)
connects gut tube to yolk sac.
Gut divided into fore-, mid-, and
hindgut = closed at the cranial
(buccopharyngeal membrane)
and caudal (cloacal membrane)
ends.
Homeobox genes = contain
conserved DNA binding motif;
grouped into four clusters;
regulate anterior-posterior
patterning of embryo.
Cloaca = expanded portion of
hindgut = allantois forms off of
cloaca = later forms bladder.

Placenta
The placenta is formed by the chorion of the embryo and the
endometrium of the uterus; the umbilical cord connects the fetus to the
placenta.
Fetal blood does not mix with maternal blood; fetal capillaries are
within maternal blood sinuses; this is the site of exchanges between
maternal and fetal blood.

Placenta
Umbilical Cord
Two umbilical arteries carry
blood from the fetus to the
placenta; fetal CO2 and waste
products diffuse into maternal
blood; oxygen and nutrients
enter fetal blood.
Umbilical vein returns blood
from placenta to fetus.
The placenta is delivered after
the baby and is called the
afterbirth.

Placental Hormones
hCGsecreted by the chorion; maintains the corpus luteum so
that it secretes estrogen and progesterone during the first few
months of gestation. The corpus luteum is too small to secrete
sufficient hormones to maintain a full-term pregnancy.
Estrogen and progesterone secretion begins within 4 to 6 weeks
and continues until birth in amounts great enough to sustain
pregnancy.
Estrogen and progesterone inhibit FSH and LH secretion during
pregnancy and prepare the mammary glands for lactation.
Progesterone inhibits contractions of the myometrium until just
before birth, when progesterone secretion begins to decrease.
Relaxin inhibits contractions of the myometrium and permits
stretching of the pubic symphysis.

Embryonic Period: Week 3
At this point, the blastocyst, or developing
embryo, is looking for a spot to implant in
the uterus. Early formation of the central
nervous system, backbone, and spinal
column has begun. The gastrointestinal
system has also begun to develop with the
kidneys, liver, and intestines forming. The
heart has begun to form
Embryonic Period: Week 4
Hormones produced by the embryo stop the
mothers menstrual cycle.
Fetal Period: Week 5
The embryos tiny heart begins to beat by day
twenty-one. The brain has developed into 5
areas and some cranial nerves are visible. Arm
and leg buds are visible and the formation of the
eyes, lips, and nose has begun. The spinal cord
grows faster than the rest of the body giving a
tail like appearance which disappears as the
embryo continues to grow. The placenta begins
to provide nourishment for the embryo.

Fetal Period: Week 7
Major organs have all begun to form. The embryo has
developed its own blood type, unique from the mothers.
Hair follicles and nipples form and knees and elbows are
visible. Facial features are also observable. The eyes
have a retina and lens. The major muscle system is
developed and the embryo is able to move.
Fetal Period: Week 8
The embryo is reactive to its environment inside the
amniotic sac where it swims and moves. Hands and feet can
be seen. At the end of week 8, the embryonic period is over
and the fetal stage begins.

Fetal Period: Week 9-12
The heart is almost completely developed and the heart
rate can be heard on a Doppler machine at the doctors
office. Most major organs and tissues have developed
and red blood cells are now produced in the liver. The
face is well formed and the eyes are almost fully
developed. The eyelids will close and not reopen until the
28
th
week. Arms, hands, fingers, legs, feet, and toes are
fully formed. Nails and earlobes start to form and tooth
buds develop in the gums. Fetus can make a fist with its
finger. Testosterone (male sex hormone) is produced by
the testes in male fetus
Second Trimester
Fetal Period: Week 13-16
The brain is fully developed and the fetus can suck, swallow, and
make irregular breathing sounds. Fetus can feel pain (New England
Journal of Medicine). Fetal skin is almost transparent. Muscles
tissue is lengthening and bones are becoming harder. Liver and
organs produce appropriate fluids. Eyebrows and eyelashes appear
and the fetus makes active movements including kicks and even
somersaults.

Fetal Period: Week 20
Quickening (when the mother can feel the fetus
moving) usually occurs around this time. Finger and
toenails appear. Lanugo, a fine hair now covers the
entire body. The fetus can hear and recognize the
mothers voice. Sex organs are visible on ultrasound
devices.

Third Trimester
Fetal Period: Week 24
A protective waxy substance called Vernix covers the
skin. By birth, most of the Vernix will be gone but any
that is left is quickly absorbed. Fetus has a hand and
startle reflex. Footprints and fingerprints are forming.
Fetus practices breathing by inhaling amniotic fluid into
its developing lungs.

Fetal Period: Week 25-28
Rapid brain development occurs during this period and
the nervous system is able to control some bodily
functions. The fetus eyelids now open and close. At 25
weeks there is a 60% chance of survival if born. The fetus
is considered legally viable at 28 weeks and there is a
90% chance of survival if born at this point.
FetalPeriod: Week 29-32
There is a rapid increase in the amount of body fat the
fetus has. Rhythmic breathing occurs, but the lungs are
not yet mature. The fetus sleeps 90-95% of the day. At
this point there the survival rate is above 95% if the baby
is born.

Fetal Period: Week 38-40
The fetus is considered full-term. Lanugo is gone except on upper
arms and shoulders. Hair on the babys head is now coarser and
thicker. The lungs are mature. The average weight of the baby at this
point is seven and a half pounds. At birth the placenta detaches from
the uterus and the umbilical cord will be cut as the baby takes his first
breaths of air. Breathing will trigger changes in the heart and bypass
arteries forcing all blood to now travel through the lungs.


Digesty system
Digesty system
Respiratory system
Nervous system
Urinary system
Organogenesis of reproductive system
Organogenesis of reproductive system
Development of Ovary
Organogenesis of Uterus and Vagina
Development of External Genitalia
Development of External Genitalia
Development of External Genitalia
69
Textbook
Langman's Medical Embryology by T.W. Sadler,
9
th
ed. Lippincott, Williams and Wilkins, 2004
Gynaecology Ilustrated by D.M. Hart and J.
Norman, 5
th
ed. Churchill-Livingstone, 2000