postgraduate surgery presentation

1. INTRODUCTION TO
EMBRYOLOGY
Presenter: Dr Pashi V. M
Moderator: Prof Munkonge

2. INTRODUCTION
Embryology (Gr. έμβρυον, embryo + logos, study)
 general embryology (embryogenesis)
 special embryology (organogenesis)
 prenatal development
 280 days, 10 months:
 embryonic period (embryo)
ofrom fertilization to 8th week of development
 preembryonic period (early development) –
from the fertilization to 2nd week of gesta
 embryonic period
(late development) – from the 3rd week to
the end of 2nd month
 fetal period (fetus) – from the 9th developmental week to
the birth

3. Sex cells (gametes)
• Reproductive tissue:
–A separate tissue
–Kind of epithelial tissue
• Composition:
–Sex cells (gametes) – male and female
–“somatic” cells
• Embryonic origin
–Premordial germ cells (gonocytes)
• Formation of epiblast – 2nd week of gestation
• Movement to the wall of the yolk sac – 3rd week

4. • Migration toward the developing gonads – 5th week
• Formation of primary sex cords
• Sex differentiation – male and female
• gametogenesis

5. GAMETOGENESIS
Conversion of germ cells into male and female
gametes
The cell division that take place in the germ
cells to generate male and female gametes is
meiosis
Cytodifferentiation
Types of gametogenesis
Spermatogenesis
oogenesis

9. spermatogenesis
Spermatogonium > mature spermatozoon
Process duration – 64 days
Spermatocytopoiesis – in seminiferous tubules
of the testis:
Dividing of spermatonia by mitosis
(spermatocytogenesis)
Growth and maturation by meiosis
Cytodifferentiation of spermatids into
spermatozoa (spermiogenesis)

12. Peculiarities of spermatogenesis
Maturation of sperms begins at puberty
Wavy and continuously course to a ripe old
age
Two meiotic divisions without interphase
Four mature spermatozoa are formed from
one spermatogonium
Only after their separation from the residual
bodies can the spermatozoa be considered
isolated cells

13. Spermiogenesis
Spermatid > mature spermatozoon
Process duration – 24 days
3 phases
Golgi phase
 Proacrosomal granule
Acrosomal phase
 Acrosomal vesicle
 Acrosome – hydrolytic enzymes:
 Hyaluronidase
 Neuraminidase
 Acid phosphatase
 Acrosin (zonalysin)

14. Maturation phase
 Residual bodies are shed
 Formation of spermatozoa
 Release of mature spermatoza > spermiation

15. Spermatozoon
Mature male gamate
Total length – 58-67um
Structure:
Head
Nucleus
Acrosomal cap
Neck
Covered by plasmalema
Basal body - proximal centriole

16. Tail – flagellum
 Middle piece
 Principal piece
 End piece

17. Female gametes
Follicular cells
 Secretory role
 Endocrine secretion – estrogens
 Ovulation > lutein cells – progesterone
Theca cells
Build up the theca interna
Interstitial cells
Hilus cells
Produce testosterone

18. Oocytes
Oogonia – mitotically active cells
Primary oocyte
Secondary oocyte
ovum

19. Oogenesis
Prenatal stage
Period of proliferation – gonocytes
Oogonia - 7 million /5th month
Primary oocyte – 700000 – 2 million
Postnatal stage
Growth - primary oocyte, remain in P of meiosis 1

20. Percliarities of oogenesis
first miotic division begins during fetal life and
is completed just before ovulation
Meiosis II is completed only if the oocyte is
fertilized
One mature oocyte (ovum) and three polar
bodies are formed from one oogonium

22. Fertilization
• Fertilization is the fusion of spermatozoa with
the mature ovum
• Capacitation and acrosome reaction
• Capacitation enables the sperm cell to interact
with uterine cells
• Acrosome reaction is important for
penetration of the spermatozoa through the
zona pellucida

23. Corona radiata
Zona pellucida
(ZP-1, -2, and -3)
Cortical granules
The egg (and corona radiata) at ovulation

24. Fertilization continues
• Fertilization has 3 phases
• Penetration of the Corona Radiata
• Penetration of the Zona Pellucida
• Fusion of the Oocyte and Sperm Cell
Membranes
– Cortical and zona reactions
– Resumption of the second meiotic division

27. Fertilization continues
• The main results of fertilization are as follows:
• Restoration of the diploid number of
chromosomes
• Determination of the sex of the new individual
• Initiation of cleavage

28. 1. Acrosome Rx
sperm bind to ZP proteins in the
zona pellucida; this initiates the
release of enzymes from the
sperm allowing it to burrow
through the zona pellucida.
2. Zona Rx
binding of the sperm and egg
plasma membranes initiates Ca+
influx into the egg and release of
cortical granules from the egg
that block other sperm from
fertilizing the egg.
Fertilization is a multi-step process whereby multiple sperm bind to the
corona radiata, but only a single sperm usually fertilizes the egg

29. This so-called cortical reaction prevents other sperm
from fertilizing the egg (aka “polyspermy”)
Cortical granule
enzymes digest ZP
proteins so other sperm
can no longer bind.
Hyaluronic acid and
other proteoglycans are
also released that
become hydrated and
swell, thus pushing the
other sperm away.

30. Meiosis II complete
Formation of male and
female pronuclei
Decondensation of male
chromosomes
Fusion of pronuclei
Zygote
Fertilization

31. Transport through the oviduct
At around the midpoint of the
menstrual cycle (~day 14), a
single egg is ovulated and
swept into the oviduct.
Fertilization usually occurs in
the ampulla of the oviduct
within 24 hrs. of ovulation.
Series of cleavage and
differentiation events results in
the formation of a blastocyst by
the 4th embryonic day.
Inner cell mass generates
embryonic tissues
Outer trophectoderm
generates placental tissues
Implantation into the uterine
wall occurs ~6th embryonic day
(day 20 of the menstrual cycle)

32. Week 1: days 1-6
• Fertilization, day 1
• Cleavage, day 2-3
• Compaction, day 3
• Formation of blastocyst, day 4
• Ends with implantation, day 6

33. Fertilized egg
2 polar bodies
2 pronuclei
Day 1
0.1 mm
Fertilized egg (zygote)

34. Cleavage
Cleavage = cell division
Goals: grow unicellular
zygote to multicellular embryo.
Divisions are slow: 12 - 24h ea
No growth of the embryo-
stays at ~100 um in diameter
Divisions are not synchronous
Cleavage begins about 24h after
pronuclear fusion

35. 2 Cell Stage
Individual cells = blastomeres
Mitotic divisions maintain
2N (diploid) complement
Cells become smaller
Blastomeres are equivalent (aka totipotent).

36. 4 cell; second cleavage
4 equivalent blastomeres
Still in zona pellucida

37. 8 Cell;
third
cleavage
Blastomeres still
equivalent

38. Embryo undergoes compaction after 8-cell stage:
first differentiation of embryonic lineages
Caused by increased cell-cell adhesion
Cells that are forced to the outside of the morula are destined
to become trophoblast--cells that will form placenta
The inner cells will form the embryo proper and are called
the inner cell mass (ICM).

39. Formation of the blastocyst
Sodium channels appear on the surface of the outer trophoblast cells;
sodium and water are pumped into the forming blastocoele. Note that
the embryo is still contained in the zona pellucida.

41. Early blastocyst
Day 3
Later blastocyst
Day 5
blastocoele
inner cell mass

42. Monozygotic twinning typically occurs
during cleavage/blastocyst stages

43. “Hatching” of the blastocyst:
preparation for implantation
Hatching of the embryo from the zona pellucida occurs just
prior to implantation. Occasionally, the inability to hatch
results in infertility, and premature hatching can result in abnormal implantation in the
uterine tube.

44. Ectopic
Implantation
Implantation somewhere
other than upper portion
of uterus
“Rupture” can lead to life-
threatening hemorrhage

46. Tubal pregnancy

47. Week 2: days 7-14
implantation
• Implanted embryo becomes more deeply
embedded in endometrium
• Further development of trophoblast into
placenta
• Development of a bi-laminar embryo,
amniotic cavity, and yolk sac.

48. Implantation and placentation (day 8)
Trophoblast further differentiates and invades maternal tissues
– Cytotrophoblast: stem cell population
– Syncytiotrophoblast: invasive fused cells (syncytium) derived from cytotrophoblast
– Breaks maternal capillaries, trophoblastic lacunae fill with maternal blood
Inner cell mass divides into epiblast and hypoblast:
– Epiblast contributes to forming the overlying amniotic membrane and amniotic cavity
– Hypoblast contributes to forming the underlying yolk sac.

49. Implantation and placentation (day 9)
Trophoblast further differentiates and invades maternal tissues
– Cytotrophoblast: stem cell population
– Syncytiotrophoblast: invasive fused cells (syncytium) derived from cytotrophoblast
– Breaks maternal capillaries, trophoblastic lacunae fill with maternal blood
Inner cell mass divides into epiblast and hypoblast:
– Epiblast contributes to forming the overlying amniotic membrane and amniotic cavity
– Hypoblast contributes to forming the underlying yolk sac.

50. Implantation and placentation (day 12)
Trophoblast further differentiates and invades maternal tissues
– Cytotrophoblast: stem cell population
– Syncytiotrophoblast: invasive fused cells (syncytium) derived from cytotrophoblast
– Breaks maternal capillaries, trophoblastic lacunae fill with maternal blood
Inner cell mass divides into epiblast and hypoblast:
– Epiblast contributes to forming the overlying amniotic membrane and amniotic cavity
– Hypoblast contributes to forming the underlying yolk sac.

51. Implantation and placentation (day 13)
Trophoblast further
differentiates and invades
maternal tissues
– Cytotrophoblast: stem cell
population
– Syncytiotrophoblast: invasive
fused cells (syncytium) derived
from cytotrophoblast
– Breaks maternal capillaries,
trophoblastic lacunae fill with
maternal blood
Inner cell mass divides into
epiblast and hypoblast:
– Epiblast contributes to forming
the overlying amniotic
membrane and amniotic cavity
– Hypoblast contributes to
forming the underlying yolk sac.

52. Week 3: Days 14-21
• Two layer germ disc
• Primitive streak forms
• Gastrulation forms tri-laminar embryo
• Neural induction
• Left-right asymmetry
• 0.4mm - 2.0mm

54. Gastrulation
At gastrulation the two layered epiblast is converted
into the three primary embryonic germ layers:
– Ectoderm: outside, surrounds other layers later in
development, generates skin and nervous tissue
– Mesoderm: middle layer, generates most of the
muscle, blood and connective tissues of the body and
placenta
– Endoderm: eventually most interior of embryo,
generates the epithelial lining and associated glands of
the gut, lung, and urogenital tracts

55. The human embryo at gastrulation

56. At gastrulation, primitive endoderm is replaced by
definitive or embryonic endoderm then mesoderm
is formed

57. Cell movements during gastrulation

58. Axial mesoderm: passes
through the node and migrates along
the midline –forms the notochord
Paraxial mesoderm: passes
just caudal to the node and migrates
slightly laterally –forms cartilage,
skeletal muscle, and dermis
Lateral plate mesoderm:
passes more caudal and migrates
more laterally –forms circulatory
system and body cavity linings.
Extraembryonic mesoderm:
passes most caudal and migrates
most laterally –forms extraembryonic
membranes and associated
connective tissue & blood vessels.
Mesoderm is patterned in a cranial to caudal gradient

59. The notochord and pre-chordal plate develops from mesoderm arising from cells that passed
directly through the node and migrated cranially along the midline
The notochord and pre-chordal plate are important signaling centers that pattern the
overlying ectoderm and underlying endoderm.
Fate of the “axial” mesoderm

60. Major signaling centers at gastrulation:
the node and the anterior visceral endoderm (AVE)
• Primitive node positions primitive streak for gastrulation, induces neural differentiation
• AVE from primitive endoderm secretes factors that position primitive streak in posterior, induce head
formation

61. The node also sets up the neural plate

62. Left-Right asymmetry is established at
gastrulation
Leftward beating of cilia at node moves
secreted molecules sonic hedgehog (Shh)
& FGF-8 to the left side of embryo.
Causes left side genes Nodal and Pitx2 to
be expressed which then pattern
developing organs.
If cilia are defective, Shh and Fgf8 can
randomly end up on right side, resulting in
reversal of symmetry, aka situs inversus
(liver on the left, spleen on the right, etc.)
Situs can be complete (everything
reversed) or partial (only some organs
reversed).

63. Situs Inversus

64. What happens if there is “not enough” gastrulation?
Caudal agenesis (sirenomelia)
Premature regression of the primitive streak leads to widespread loss of trunk
and lower limb mesoderm.
VATeR association:
Vertebral defects
Anal atresia
Tracheo-esophageal fistula
Renal defects
VACTeRL association:
those above plus…
Cardiovascular defects
Limb (upper) defects

65. If the primitive streak fails to regress, multipotent primitive streak cells can develop into
multi-lineage tumors (containing ecto-, meso-, and endodermal tissues).
What happens if there is “too much” gastrulation?
Sacrococcygeal teratoma

66. THE EMBRYONIC PERIOD
 The period in which each of the three germ layers
will give rise to a number of specific tissues and
organs
Ectodermal germ layers
 Initially the ectodermal germ layer has shape of a
disc, not equal at caudal and cranial points
 Notocord and precordal mesoderm induces
overlying ectoderm to thicken and form the
neuro plate
 Induction of neuroectoderm is the initiation of
neurulation

67. Neurulation
 Process by which neuro tube is formed from
neuro plate
 Lateral edges of neuro plates are elevated are
elevated to form the neuro fold while the
depression makes the neuro groove
 Neuro folding results in formation of a neural
tube
 Communication with amniotic cavity through
neuropores
 Closure of neuropores marks end of
neurulation

72. Neural crest cells
 These are cells at the lateral border of the
neuroectoderm
 During fusing of the neuro folds the cells will
undergo the epithelial to mesenchymal
transition
 Migrates from neuroectoderm to underlying
mesoderm
 Neuro crest cells of the trunk region start
migrating in 2 directions following closure of
the neuro tube
• Dorsal and ventral

74. • Ectoderm germ layer gives raise to organs and
structures that maintain contact with the
outside world

76. Mesodermal germ layer
 Mesodermal germ layer tissue under goes
proliferation
 Midline form a thickened tissue known as
paraxial mesoderm
 Laterally remain thin and called lateral plate
 Lateral plate divides into somatic or parietal
mesoderm layer continuous with amnion
 The layer continuous with the yolk sac is the
splanchnic or visceral mesoderm layer

77. • Paraxial mesoderm
• Segmental organization known as somitomeres
and form in a cephalocaudal manner
• Somitomeres further organise into somites
• First pair arise from the occipital region at
approximately 20th day of development then they
appear at the rate of 3 pairs per day until week 5
• 42 to 44 pairs are present, 4 occipital, 8 cervical,
12 thoracic, 5 lumber, 5 sacral and 8 to 10
coccygeal pairs
• Age determination

81. Intermediate mesoderm
• Forms segmental cell clusters, future
nephrotome
• More caudally it forms an unsegmented mass of
tissue, the nephrogenic cord
• Excretory units of the urinary system and gonads
form
Lateral plate mesoderm
• Differentiate into visceral and parietal mesoderm

83. Blood and blood vessels
 Blood vessels form in two ways,
vasculogenesis, where by blood vesselsarise
from blood islands and angiogenesis,
sprouting from existing blood vessels
 The first blood island appear in mesoderm
sorrounding the wall of yolk sac at 3 weeks
 Islands arise from mesodermal cell that are
induced to form hemangioblasts
 Definitive hematopoeitic stem cells > aorta-
gonad-mesonephros region (AGM)

86. Endodermal germ layer
 The gastrointestinal tract is the main organ
system derived from the endodermal germ layer
 the epithelial lining of the respiratory tract
 the Parenchyma of the thyroid, parathyroids,
liver, and pancreas
 the reticular stroma of the tonsils and thymus
 the epithelial lining of the urinary bladder and
urethra
 the epithelial lining of the tympanic cavity and
auditory tube

90. References
• Langmans’s Medical Embryology, 12th ed
• Phillip M. Ecker et al, An animated tour of
human development, version 1.1.
• www.slideshare.net/bindmadhuli/embryology