Hybridoma Technology ( Production , Purification , and Application )
embryology.pptx
1.
2. Embryology
• is the study of embryos; (prenatal development of
embryos and fetuses).
• Developmental anatomy:
– is the field of embryology
– concerned with the changes that cells, tissues, organs,
and the body as a whole undergo from a germ cell of
each parent to the resulting adult.
• Teratology:
– is division of embryology and pathology.
– deals with abnormal development (birth defects).
2
3. EMBRYOLOGIC TERMINOLOGY
• Oocyte (ovum, egg):
– female germ or sex cells, are produced in the ovaries.
• Sperm (sperma, seed)
– male germ cell produced in the testes (testicles).
• Zygote:
– results from the union of an oocyte and a sperm during
fertilization.
– is the beginning of a new human being.
• Cleavage
– is series of mitotic cell divisions of the zygote
– result in the formation of early embryonic cells, blastomeres
• Morula
– solid mass of 12-32 blastomeres.
– occurs 3 to 4 days after fertilization, just as the early embryo
enters the uterus.
3
4. • Blastocyst
– is when morula consist fluid filled cavity with in it.
• Implantation.
– process during which the blastocyst attaches to the endometrium,
– Occurs approximately 6 days after fertilization.
• Gastrula: three germ layered during 3rd wk..
• Neurula: The early embryo during the 3rd-4th weeks when
– neural tube is developing from the neural plate.
• Embryo:
– its early stages of human development.
– extends to the end of the eighth week (56 days).
• Fetus (unborn offspring):
– After the embryonic period (8 weeks) and until birth
• Conceptus (L. conceptio, derivatives of zygote):
– embryo and its adnexa or associated membranes.
4
5. Induction and organ formation
• Organs are formed by interactions between cells and
tissues.
• Induction: one group of cells or tissues causes another
set of cells or tissues to change their fate.
– Inducer: cell or tissue that produces a signal.
– Responder: one respond to that signal.
Cell signaling
• Cell-to-cell signaling is essential for:
– induction,
– for conference of competency to respond,
– and for crosstalk between inducing and responding cells.
• These lines of communication are established by:
– paracrine interactions:
– Juxtacrine interactions
5
6. Juxtacrine Signaling
• mediated through signal transduction pathways as
well but does not involve diffusible factors.
• Occur in three ways
1. protein on one cell surface interacts with a receptor on
an adjacent cell in a process analogous to paracrine
signaling
2. Ligands in the extracellular matrix secreted by one cell
interact with their receptors on neighboring cells.
3. There is direct transmission of signals from one cell to
another by gap junctions.
• The junctions themselves are made of connexin proteins.
6
7. Paracrine Signaling Factors
• proteins synthesized by one cell diffuse over short
distances to interact with other cells
– These are called: paracrine factors or growth and
differentiation factors (GDFs).
• Most are grouped into four families, and members
of these same families are used repeatedly to
regulate development and differentiation of organ
systems.
– fibroblast growth factor (FGF),
– WNT, hedgehog, and
– transforming growth factor-b (TGF-b) families.
7
8. Fibroblast Growth Factors (they stimulate the
growth of fibroblasts)
• approximately two dozen FGF genes that have been
identified, and they can produce hundreds of
protein isoforms by altering their RNA splicing or
their initiation codons.
• FGFs are particularly important for:
–angiogenesis,
–axon growth,
–and mesoderm differentiation.
•For example, FGF8 is important for
development of the limbs and parts of
the brain.
8
9. Hedgehog Proteins
• gene was named because it coded for a pattern of
bristles on the leg.
• are three hedgehog genes in mammals:
– Desert, Indian, and sonic hedgehog.
• Sonic hedgehog:
– is involved in a number of developmental events
including:
• limb patterning, neural tube induction
• and patterning, somite differentiation,
• Gut regionalization
9
10. WNT Proteins
• Are involved in regulating limb patterning, midbrain
development, and some aspects of somite and
urogenital differentiation among other actions.
The TGF-b Superfamily
TGF-b superfamily has more than 30 members
– includes the TGF-bs,
– the bone morphogenetic proteins,
– the activin family,
– The Mullerian inhibiting factor (MIF)
10
11. Gametogenesis
-is a process of formation of specialized sex cells
(gametes)
• Gametes:
– Are formed from germ cells
• Primordial Germ Cells :
– Are formed in the epiblast during 2nd week and migrate
to yolk sac.
– During 4th week they begin to migrate the developing
gonads up to 5th week.
– Their no. increased by mitotic division during their
migration.
– In preparation for fertilization germ cells undergo
gametogenesis.
11
12. - Meiosis:-
- is a special type of cell division that involves two meiotic
cell divisions.
– takes place in the germ cells to generate male and
female gametes,
– requires requires two cell divisions, meiosis I and
meiosis II,
• Meiosis I:
– male and female germ cells (spermatocytes and primary
oocytes) at the beginning of replicate their DNA
– In contrast to mitosis, however, homologous
chromosomes then align themselves in pairs, (synapsis)
– Homologous pairs then separate into two daughter cells,
– Thereby reducing the chromosome number from
diploid to haploid.
12
14. Meiotic division II
• Occur without normal interphase (without
intervening step of DNA replication)
• Each chromosome divides and each half, or
chromatid is drawn to a different pole, thus the
haploid no. of chromosome (23) is retained and each
daughter cell formed by meiosis has the reduced
haploid no. of chromosomes.
Why Meiosis
• Provides constancy of chromosome no.
• Allows random assortment of maternal and paternal
chromosomes b/n gametes.
• Provides variability of Human species.
14
15. Polar Bodies
• Are cells that receive little amount of cytoplasm during meiosis of
primary oocyte.
• As a result one primary oocyte give rise to four daughter cells (
3polar bodies + 1 mature gamete), each with 22+ 1X.
• Polar bodies will not develop to mature gamete.
15
16. Chromosomal abnormalities
• May be numerical or structural.
Numerical abnormalities:
• Euploid: any exact multiple of n (e.g, diploid or
triploid)
• Aneuploid: is when an extra chromosome is present
or when one is missing.
– May occur during meiotic division.
– may rise if separation does not occur (nondisjunction)
thus both members of a pair move into one cell.
– Resulting one cell with 24 chro. and other with 22 chro.
– The incidence increases in women > 35yrs old.
16
17. • Nondisjunction occasionally occur during mitosis in an
embryonic cell during the earliest cell divisions.
• Result in mosaicism. 17
19. Translocation:
• When chromosomes break and piece of one chromosome
attach to another.
• Are common particularly between chromosomes, 13, 14, 15,
21, and 22.
Trisomy 21 (Down syndrome)
• Is an extra copy of chromosome 21 (trisomy 21).
• Risk increases with age (1 in 300 at 35 yrs and 1 in 100 >
40yrs).
• Features:
– Growth retardation
– Intellectual disabilities, Mental deficiency
– Craniofacial abnormalities
– Extra skin folds at the medial corners of the eyes, upward slant to
palpebral fissures.
– Small ears, cardiac defects, and hypotona.
– Brachycephaly, flat nasal bridge.
– Protruding tongue 19
22. Trisomy 18 (Edwards syndrome )
• The incidence is approximately 1 in 5000 newborns.
Features:
– Intellectual disabilities, growth retardation.
– Congenital heart defects, short sternum
– Low-set ears, prominent occiput
– Flexion of fingers and hands.
– Renal anomalies, syndactly (fused digits).
– Micrognathia (small jaw), hypoplastic nails.
.
22
23. • Female neonate with
trisomy 18.
• Note:
– the growth retardation,
– clenched fists with
characteristic positioning
of the fingers (second and
fifth ones overlapping the
third and fourth),
– short sternum, and
narrow pelvis.
23
24. Trisomy 13 (Patau
syndrome )
• Deafness, bilateral cleft
lip and palate
• Eye defects:
micro/anophthalmia,
coloboma.
• Severe CNS
malformation
• Polydactyly (with more
digits), malformed ears
24
25. trisomy 13.
Note the:
• bilateral cleft lip,
• low-set malformed
left ear,
• and polydactyly
(extra digits).
• A small
omphalocele
(herniation of
viscera into
umbilical cord) is
also present.
25
26. Klinefelter's syndrome (47,
XXY)
• small testes, hyalinization
of seminiferous tubules;
aspermatogenesis
(sterility);
• often tall with
disproportionately long
lower limbs.
• Intelligence is less than in
normal siblings.
• Approximately 40% of
these males have
gynecomastia. 26
27. Turner Syndrome (45, X )
• 1 in 8000 live births.
• Approximately 1% of monosomy X female embryos
survive.
• The phenotype is female
• Secondary sexual characteristics do not develop in 90%
of affected girls,
• is the most common cytogenetic abnormality observed
in live-born humans and fetuses that abort
spontaneously
• accounts for approximately 18% of all abortions caused
by chromosome abnormalities.
• is in the paternal gamete (sperm) in approximately 75%
of cases.
27
28. • A at birth: loose skin at posterior of the neck, short
neck, malformed ears, and swelling in the hand.
• C. Foot by lymphedema
• D. webbed neck, and widely spaced nipple
28
29. • 14-year-old girl(figure below).
• Note the:
– short stature, webbed neck,
absence of sexual maturation,
– widely spaced nipples, and
lymphedema of the hands and
feet.
47, XYY Male
• 1:1000, normal in appearance;
• usually tall; often exhibit aggressive
behavior
47, XXX Female
• 1:1000, normal in appearance;
• usually fertile; 15%-25% are mildly
mentally retarded. 29
30. Structural Chromosomal Abnormalities
• result from chromosome breakage
• Result depends on what happens to the broken pieces
(deletions, inversion, or translocation).
• may be induced by various environmental factors, for
example, radiation, drugs, chemicals, and viruses.
1. Translocation:
– transfer of a piece of one chromosome to a nonhomologous
chromosome.
2. Reciprocal translocation:
– when two nonhomologous chromosomes exchange pieces.
3. Deletion: When a chromosome breaks, part of it may
be lost 30
31. Cri du chat syndrome:
• partial terminal deletion from the short arm of chromosome
5.
• Features:
– a weak catlike cry, microcephaly (abnormally small head),
– severe mental deficiency (retardation), and congenital heart
disease.
Prader-Willi syndrome (PWS),
• Is microdeletion of long arm of paternal chromosome 15
• Features:
– short stature, mild mental retardation, obesity, hyperphagia
(overeating), and hypogonadism (inadequate gonadal function).
Angelman syndrome (AS),
• Microdeletion of long arm of maternal chr. 15
• characterized by:
– severe mental retardation, microcephaly,
– brachycephaly (short and broad head), seizures, and ataxic (jerky)
movements of the limbs and trunk. 31
33. A, Reciprocal translocation.
B, Terminal deletion.
C, Ring chromosome.
D, Duplication.
E, Paracentric inversion.
F, Isochromosome.
G, Robertsonian translocation.
33
34. Spermatogenesis
• A sequence by which spermatogonia is transformed to
mature sperms.
• This process begins at puberty.
Spermatogonia primary spermatocyte reduction
division of 1st division 2ry haploid spermatocytes
undergo 2ry division four haploid spermatids.
- This spermatids gradually changed to 4 mature sperm
by process called spermiogenesis.
- When complete, sperms enter the lumina of the
seminiferous tubules.
- Sartoli cells:- lines seminiferous tubules.
- support and nurture the germ cells.
- Sperms are transported passively from seminiferous
tubules to epididymis, where they become stored and
functionally mature. 34
37. Parts of sperm
• Head:- forms most of the bulk of the sperm and contains the
haploid nucleus.
• Acrosome:-
– caplike saccular organelle containing several enzymes.
– Covers anterior two thirds of the nucleus
– these enzymes facilitate dispersion of the follicular cells of the
corona radiata and sperm penetration of the zona pellucida during
fertilization.
• tail of the sperm:-
– provides the motility of the sperm that assists its transport to the
site of fertilization.
– consists of three segments: middle piece, principal piece, and end
piece
• middle piece: contains mitochondria, which provide the adenosine
triphosphate necessary for activity.
• Neck of the sperm is the junction between the head and tail.
37
38. Oogenesis (ovogenesis):
• is the sequence of events by which oogonia are transformed
into mature oocytes.
• begins before birth and is completed after puberty.
• continues to menopause.
Prenatal Maturation of Oocytes
• early fetal life oogonia proliferate by mitosis.
• Oogonia enlarge to form primary oocytes before birth;
• As a primary oocyte forms connective tissue cells surround
it and form a single layer of flattened, follicular epithelial cells
(primordial follicle) .
• As the primary oocyte enlarges during puberty, the follicular
epithelial cells become cuboidal in shape and then columnar,
forming a primary follicle.
• The primary oocyte soon becomes surrounded by a covering
of amorphous acellular glycoprotein material, the zona
pellucida.
38
40. • The primary oocyte soon becomes surrounded by a
covering of amorphous acellular glycoprotein material,
the zona pellucida.
• Primary oocytes begin the first meiotic division before
birth, but completion of prophase does not occur until
adolescence.
• The follicular cells surrounding the primary oocyte are
believed to secrete a substance, oocyte maturation
inhibitor, which keeps the meiotic process of the oocyte
arrested.
40
41. Postnatal Maturation of Oocytes
• Begins during puberty, usually one follicle matures each month
and ovulation occurs.
• The long duration of the first meiotic division (up to 45 years) may
account in part for the relatively high frequency of meiotic errors,
such as nondisjunction.
• No primary oocytes form after birth.
• As a follicle matures, the primary oocyte increases in size and,
shortly before ovulation, completes the first meiotic division to
give rise to a secondary oocyte and the first polar body.
• the division of cytoplasm is unequal.
secondary oocyte
• receives almost all the cytoplasm and the first polar body receives
very little.
• At ovulation, the nucleus of the secondary oocyte begins the
second meiotic division, but progresses only to metaphase.
• If a sperm penetrates the secondary oocyte, the second meiotic
division is completed, and most cytoplasm is again retained by one
cell, the fertilized oocyte. 41
42. • Approximately:
– newborn: two million primary oocytes in the ovaries,
– Adolescence: no more than 40,000 remain.
– Of these, only 400: become secondary oocytes and are expelled at
ovulation during the reproductive period.
• zona pellucida:
– surround primary oocyte
– Is amorphous acellular glycoprotein material.
COMPARISON OF GAMETES
Oocytes
• massive and immotile
• surrounded by the zona pellucida and
a layer of follicular cells (corona radiata)
•has an abundance of cytoplasm
containing yolk granules
•only one kind of normal secondary
oocyte: 23, X
Sperm
• Microscopic and highly
motile
•two kinds of normal
sperm: 23, X and 23, Y
42
43. Female Reproductive systems
• uterus (Latin [L.], womb):
– consist of three layers :
• Perimetrium: thin external layer
• Myometrium: thick smooth muscle layer
• Endometrium: thin internal layer
• Endometrium has 2 layers microscopically:
1. Basal layer:
– is not sloughed off during menstruation.
– containing the blind ends of the uterine glands
2. Functional layer:
– disintegrate and shed during menstruation and after
parturition 43
44. Has two parts
1. spongy layer: thick, composed
of edematous connective
tissue
• contains the dilated,
tortuous bodies of the
uterine glands
2. Compact layer: thin consisting
of densely packed connective
tissue around the necks of the
uterine glands 44
45. • MENSTRUAL (endometrial) CYCLE
– is the time during which the oocyte matures, is
ovulated, and enters the uterine tube.
– In 90% of women, it ranges b/n 23-35dys (28d average).
– is a continuous process
• Phases of the Menstrual Cycle
– Menstrual Phase:
• functional layer is sloughed off and discarded
• menstrual flow-menses (monthly bleeding),
• usually lasts 4 to 5 days.
45
46. • Proliferative (follicular, estrogenic) Phase:
– lasting approximately 9 days,
– growth of ovarian follicles and is controlled by
estrogen secreted by these follicles.
– 2-3 fold increase in the thickness of the
endometrium.
– surface epithelium reforms and covers the
endometrium.
– glands increase in number and length, and the spiral
arteries elongate.
• Luteal (secretory, progesterone) Phase:
– lasting approximately 13 days,
– formation, functioning, and growth of the corpus luteum.
– corpus luteum: produce progesterone that stimulates the
glandular epithelium to secrete a glycogen-rich material.
46
47. – glands become wide, tortuous, and saccular, and the
endometrium thickens:
• because of the influence of progesterone and estrogen from
the corpus luteum and because of increased fluid in the
connective tissue.
• If fertilization does not occur:
– corpus luteum degenerates.
– Estrogen and progesterone levels fall
– secretory endometrium enters an ischemic phase.
– Menstruation occurs.
47
48. • Ischemic Phase:
– occurs when the oocyte is not fertilized.
– Ischemia (reduced blood supply) occurs as the spiral
arteries constrict.
– Endometrium has a pale appearance.
• If fertilization occurs:
– Cleavage of the zygote and blastogenesis (formation of
blastocyst) occur.
– The blastocyst begins to implant in the endometrium.
– Human chorionic gonadotropin keeps the corpus luteum
secreting estrogens and progesterone.
– luteal phase continues and menstruation does not occur.
• MATURATION OF SPERMS
– Freshly ejaculated sperms are unable to fertilize oocytes.
48
49. • Capacitation: a period of sperm conditioning
– lasting approximately 7 hours.
– a glycoprotein coat and seminal proteins are removed from
the surface of the sperm's acrosome.
– membrane components of the sperms are extensively
altered.
– no morphologic changes, but they are more active.
– occurs in the uterus or uterine tubes by substances secreted
by them.
• Dispermy :
– when two sperms participate in fertilization.
– resulting in a zygote with an extra set of chromosomes.
• Triploidy (69 chromosomes):
– triploid conceptions account 20% of chromosomally
abnormal spontaneous abortions. 49
50. FERTILIZATION
• usually occurs in the ampulla of the uterine tube
• begins with contact between a sperm and an oocyte
• ends with the intermingling of maternal and paternal
chromosomes.
• takes approximately 24 hours.
Phases of Fertilization
1. Passage of a sperm through the corona radiata:
– Dispersal of the follicular cells of the corona radiata
surrounding the oocyte.
2. Penetration of the zona pellucida:
– is the important phase in the initiation of fertilization.
50
51. – action of enzymes released from the acrosome forms
pathway for sperm.
• Such as: esterases, acrosin, and neuraminidase cause lysis
of the zona pellucida.
– zona reaction:
• begins once the sperm penetrates the zona pellucida
• a change in the properties of the zona pellucida that makes it
impermeable to other sperms.
3. Fusion of plasma membranes of the oocyte and
sperm.
– break down at the area of fusion.
– head and tail of the sperm enter the cytoplasm of the
oocyte,
– sperm's plasma membrane remains behind 51
52. 4. Completion of the second meiotic division of
oocyte:
– activated when sperm penetrates the oocyte.
• Early pregnancy factor:
– an immunosuppressant protein,
– is secreted by the trophoblastic cells
– appears in the maternal serum within 24 to 48 hours
after fertilization.
– forms the basis of a pregnancy test during the first 10
days of development.
52
53. Fertilization:
– Stimulates the penetrated oocyte to complete the second
meiotic division.
– Restores the normal diploid number of chromosomes (46).
– Results in variation of the human species.
– Determines chromosomal sex of the embryo.
– Causes metabolic activation of the ootid
– initiates cleavage (cell division) of the zygote.
• X and Y sperms (gender selection) using:
– differential swimming abilities of the X and Y sperms
– Different speeds of migration of sperms in an electric field
– Differences in the appearance of X and Y sperms
– DNA difference between X and Y sperms
53
55. • CLEAVAGE OF THE ZYGOTE:
– repeated mitotic divisions of the zygote,
– result in a rapid increase in the number of cells.
– Forms embryonic cells-blastomeres.
– Morula:
• 12 to 32 blastomeres.
• forms approximately 3 days after fertilization and enters the uterus.
FORMATION OF THE BLASTOCYST
• is when a fluid-filled space (blastocystic cavity) appears inside
the morula.
• fluid passes from the uterine cavity through the zona pellucida
to form this space.
• About two days the the zona pellucida gradually degenerates
and disappears
• attaches to the endometrial epithelium 6 days after fertilization.
55
58. • these cavity separates the blastomeres into two parts:
– Trophoblast (trophe, nutrition):
• thin, outer cell layer,
• gives rise to the embryonic part of the placenta
– Embryoblast:
• centrally located blastomeres, the inner cell mass,
• gives rise to the embryo;
• it is the primordium of the embryo.
58
59. Second Week
Events:
Completion of implantation of the blastocyst.
morphologic changes in the embryoblast produce a
bilaminar embryonic disc.
composed of epiblast and hypoblast.
formation of extraembryonic structures such as:
– the amniotic cavity,
– amnion,
– umbilical vesicle (yolk sac),
– connecting stalk, and chorionic sac.
59
60. • COMPLETION OF IMPLANTATION
– completed by the end of the second week.
– endometrial cells undergo apoptosis (programmed cell
death), which facilitates the invasion.
– more trophoblast contacts the endometrium and
differentiates into:
1. Cytotrophoblast:
– inner layer of cells that is mitotically active
– forms new cells that migrate into the increasing mass of
syncytiotrophoblast.
2. Syncytiotrophoblast:
– a rapidly expanding, multinucleated mass
– no cell boundaries can be observed.
– outer layer consisting of a multinucleated protoplasmic mass
– Produce enzymes that erode the maternal tissues
– produces a hormone-human chorionic gonadotrophin (hCG),
Enough hCG is produced at the end of the second week 60
64. FORMATION OF THE AMNIOTIC CAVITY, EMBRYONIC DISC,
AND UMBILICAL VESICLE
• amniotic cavity
– small space in the embryoblast.
– a small space appears in the embryoblast (primordium of the
amniotic cavity)
– Concurrently, morphologic changes occur in the embryoblast
that result in the formation of embryonic disc.
• Amnioblasts:
– are amniogenic (amnion-forming) cells
– separate from the epiblast and form the amnion (encloses
the amniotic cavity) .
• embryonic disc:
– flat, almost circular bilaminar plate of cells
– consisting of two layers 64
65. 1. Epiblast:
• thicker layer,
• consist high
columnar cells
related to the
amniotic cavity
• forms the floor
of the amniotic
cavity
65
66. 2. Hypoblast:
• consist small
cuboidal cells
• adjacent to the
exocoelomic
cavity
• forms the roof
of the
exocoelomic
cavity (primary
umbilical
vesicle)
66
67. • extraembryonic mesoderm:
– layer of connective tissue surrounds the amnion and
umbilical vesicle.
– Formed by cells from the umblical vesicle endoderm
– derived from yolk sac cells, forma fine, loose connective
tissue
• lacunae- about 12-day embryo
– isolated cavities appear in the syncytiotrophoblast.
– soon filled with a mixture of maternal blood from
ruptured endometrial capillaries.
– the blood provides nutritive material to the embryo.
– establishes the primordial uteroplacental circulation.
– fused to form lacunar networks, giving the
syncytiotrophoblast a spongelike appearance. 67
68. • extraembryonic coelom:
– a large isolated fluid filled cavity in the extraembryonic
mesoderm
– surrounds the amnion and umbilical vesicle.
– as it forms, the primary umbilical vesicle decreases in
size and a smaller secondary umbilical vesicle forms.
– splits the extraembryonic mesoderm into two layers:
1. Extraembryonic somatic mesoderm:
– lining the trophoblast and covering the amnion
2. Extraembryonic splanchnic mesoderm:
– surrounding the umbilical vesicle
– umbilical vesicle:
• contains no yolk;
• is the site of origin of primordial germ cells. 68
70. DEVELOPMENT OF THE CHORIONIC
SAC
• Suspends embryo and its amniotic sac and umbilical vesicle by the
connecting stalk
• It’s wall is formed by chorion.
Chorion: consists of:
• extraembryonic somatic mesoderm
• two layers of trophoblast.
• The extraembryonic coelom is now called the chorionic cavity.
IMPLANTATION SITES OF BLASTOCYSTS:
• usually occurs in the endometrium of the uterus.
Placenta Previa:
Implantation of a blastocyst in the inferior segment of the uterus near the
internal os.
partially or completely covers the os
70
71. Extrauterine Implantation (ectopic pregnancies)
• 95% to 98% occur in the uterine tubes, most often in the ampulla
and isthmus.
• incidence depending on the socioeconomic level of the
population.
• one of the main cause of maternal deaths during the first
trimester.
• signs and symptoms :
– misses her menstrual period
– may also experience abdominal pain and tenderness because of
distention of the uterine tube, abnormal bleeding, and irritation of the
pelvic peritoneum (peritonitis).
– The pain may be confused with appendicitis if the pregnancy is in the
right uterine tube.
– human chorionic gonadotropin at a slower rate than normal
pregnancies;
– consequently human chorionic gonadotropin assays may give false-
negative results if performed too early.
– Transvaginal ultrasonography is very helpful in the early detection of
ectopic tubal pregnancies.
71
73. • causes of tubal pregnancy:
• factors that delay or prevent transport of the cleaving zygote to the uterus,
• E.g. by mucosal adhesions in the uterine tube
• from blockage of it that is caused by scarring resulting from pelvic
inflammatory disease.
• usually result in rupture of the uterine tube and hemorrhage into the
peritoneal cavity during the first 8 weeks, followed by death of the embryo.
73
74. • abdominal pregnancy:
– Is when blastocyst in ampulla or on fimbriae was
expelled into the peritoneal cavity where they
commonly implant in the rectouterine pouch.
– In exceptional cases, it may continue to full term and the
fetus may be delivered alive through an abdominal
incision.
– Usually, however, the placenta attaches to abdominal
organs and causes considerable intraperitoneal bleeding.
– Simultaneous intrauterine and extrauterine pregnancies
are unusual, occurring approximately 1 in 7000.
74
75. Abnormal Growth of Trophoblast
• Sometimes the embryo dies and the chorionic villi do not
complete their development; that is, they do not become
vascularized to form tertiary villi.
• These degenerating villi form cystic swellings-hydatidiform moles-
which resemble a bunch of grapes.
• The moles exhibit variable degrees of trophoblastic proliferation
and produce excessive amounts of human chorionic gonadotropin.
• Complete hydatidiform moles are of paternal origin.
• 3% to 5% of moles develop into malignant trophoblastic lesions-
choriocarcinomas.
• invariably metastasize (spread) through the bloodstream to
various sites, such as the lungs, vagina, liver, bone, intestine, and
brain.
• mechanisms for development of complete hydatidiform moles
are:
– Fertilization of an empty oocyte by a sperm, followed by duplication
(monospermic mole)
– Fertilization of an empty oocyte by two sperms (dispermic mole) 75
76. SUMMARY OF THE SECOND WEEK
• blastocyst completes its implantation in the endometrium.
• decidual reaction: endometrial changes in preparation for implantation.
• Formation of primary umbilical vesicle (yolk sac) and extraembryonic
mesoderm.
• extraembryonic coelom forms. The coelom later becomes the chorionic
cavity.
• secondary umbilical vesicle develops as primary umbilical vesicle becomes
smaller and gradually disappears.
• amniotic cavity appears as a space between the cytotrophoblast and the
embryoblast.
• embryoblast differentiates into a bilaminar embryonic disc (epiblast +
hypoblast).
• prechordal plate develops:
– a localized thickening of the hypoblast,
– indicates the future cranial region of the embryo and the future site of the mouth.
– essential in forebrain and eye induction.
– is a mesenchymal population rostral to the notochord
76
77. Third Week
• characterized by:
– appearance of primitive streak
– Development of notochord
– Differentiation of three germ layers
• GASTRULATION:
– is the beginning of morphogenesis (development of body form)
formation of germ layers
– bilaminar embryonic disc is converted into a trilaminar embryonic disc.
– is the significant event occurring during the third week.
• Embryonic ectoderm: gives rise to
– the epidermis,
– central and peripheral nervous systems,
– the eye, and inner ear, and,
– as neural crest cells to many connective tissues of the head.
– In addition, it gives rise to:
• Subcutaneous glands, mammary glands, pituitary gland and enamel of the
teeth.
77
78. • Embryonic endoderm: source of the:
– epithelial linings of the respiratory and alimentary (digestive)
tracts,
– glands opening into the gastrointestinal tract and the glandular
cells of associated organs such as the liver and pancreas.
– thyroid and parathyroid glands, thymus, liver, and pancreas
– epithelial lining of the urinary bladder and most of the urethra,
– epithelial lining of the tympanic cavity, tympanic antrum, and
pharyngotympanic (auditory) tube.
• Embryonic mesoderm: gives rise to:
– all skeletal muscles, blood cells and the lining of blood vessels,
– all visceral smooth muscular coats,
– the serosal linings of all body cavities (pericardial, pleural, and
peritoneal)
– the ducts and organs of the reproductive and excretory systems,
– and most of the cardiovascular system.
– spleen; and cortex of suprarenal glands. 78
79. Caudal dysgenesis (sirenolemia)
= result when infussicient mesoderm is formed in
caudal most region of embryo.
• Affected individuals exhibit:
– Hypoplasia and fusion of the lower limbs
– Vertebral abnormalities, renal agenesis
– Imperforate anus, and anomalities of genital organs
Situs inversus
– Is transposition of thoracic or abdominal viscera.
– Serotonin (5HT) is an important signal molecule in
establishing laterality.
– Disruption 5HT activity can result in situs inversus.
• E.g patients taking drugs like selective serotonin re-uptake
inhibitors (SSRI)
79
81. • PRIMITIVE STREAK
– first sign of gastrulation
– appears caudally in the median plane of the dorsal
aspect of the embryonic disc
– results from the proliferation and movement of cells of
the epiblast to the median plane of the embryonic disc.
– elongates by addition of cells to its caudal end.
– its cranial end proliferates to form a primitive node
• primitive groove: narrow groove develops in the
primitive streak
– is continuous with a small depression in the primitive
node-the primitive pit.
– result from the invagination (inward movement) of
epiblastic cells
81
84. – primitive streak helps to identify:
• craniocaudal axis, its cranial and caudal ends,
• dorsal and ventral surfaces,
• its right and left sides.
• Fate of the Primitive Streak
– undergoes degenerative changes and disappears by the end
of the fourth week.
• Sacrococcygeal Teratoma
– Remnants of the primitive streak.
– are the most common tumor in newborns (1 in 35,000).
NOTOCHORDAL PROCESS
• a median cellular cord
• grows cranially between the ectoderm and endoderm
until it reaches the prechordal plate.
• soon acquires a lumen, the notochordal canal. 84
87. • Notochord:
– develop from notochordal precursor cells
– extends from the oropharyngeal membrane to the
primitive node
• Defines the primordial longitudinal axis of the embryo
and gives it some rigidity
• Provides signals that are necessary for the
development of axial musculoskeletal structures and
the central nervous system
• Contributes to the intervertebral discs(nucleus
pulposus of each IVD).
• induces the overlying embryonic ectoderm to thicken
and form the neural plate.
87
88. Notochord develops as follows:
• elongates by invagination of cells from the primitive pit.
• The primitive pit extends into the notochordal process, forming a
notochordal canal forms a cellular tube that extends cranially
from the primitive node to the prechordal plate.
• Then the floor of the notochordal process fuses with the
underlying embryonic endoderm= fused layers gradually
undergo degeneration, resulting in the formation of openings
which brings the notochordal canal into communication with the
umbilical vesicle.
• The openings rapidly become confluent and the floor of the
notochordal canal disappears; the remains of the notochordal
process form a flattened, grooved notochordal plate.
• Beginning at the cranial end of the embryo, the notochordal cells
proliferate and the notochordal plate infolds to form the
notochord.
• neurenteric canal: the proximal part of the notochordal canal
– forms a transitory communication between the amniotic and umbilical
vesicle cavities.
– obliterates when development of the notochord is complete. 88
92. • cloacal membrane:
– caudal to the primitive streak
– is a circular area indicates the future site of the anus.
• oropharyngeal membrane:
– future site of the oral cavity
– have a role as a signaling center for controlling development
of cranial structures.
• embryonic disc remains bilaminar at:
– oropharyngeal membrane cranially
– In the median plane cranial to the primitive node, where the
notochordal process is located
– cloacal membrane caudally
• here the embryonic ectoderm and endoderm are fused, thereby
preventing migration of mesenchymal cells between them. 92
93. • ALLANTOIS (allas, sausage):
– appears on approximately day 16 .
– as a small, diverticulum (outpouching) from the caudal
wall of the umbilical vesicle
– extends into the connecting stalk.
– expands beneath the chorion and forms blood vessels
that will serve the placenta.
• Urachus:
– the proximal part of allantois
– extends from the bladder to the umbilical region
– is represented in adults by the median umbilical
ligament.
– It’s blood vessels become the umbilical arteries. 93
96. NEURULATION:
– formation of the neural tube.
– is the processes involved:
• in the formation of the neural plate and neural folds and closure of the
folds.
– completed by the end of the 4th wk,
– embryo may be referred to as a neurula.
• Neuropore: closure of either end.
• neural plate:
– elongated plate of thickened epithelial cells.
– Induced by underlying notochord.
– located at or adjacent to the midline.
– gives rise to the CNS-the brain and spinal cord.
• neural groove:
– On approximately the 18th day
– as neural plate invaginates along its central axis
– has neural folds on each side. 96
99. • neural folds:
– move together and fuse by the end of the 3rd wk.
– converting the neural plate into a neural tube.
• neural tube:
– the primordium of the CNS.
– separates from the surface ectoderm as the neural folds meet.
– free edges of the surface ectoderm (non-neural ectoderm) fuse so that
this layer becomes continuous over the neural tube and the back of the
embryo
• Neural crest cells:
– migrate away as the neural folds meet
– between the neural tube and the overlying surface ectoderm
– give rise to the:
• sensory ganglia of the spinal and cranial nerves.
• neurolemma sheaths of peripheral nerves
• pigment cells
• suprarenal (adrenal) medulla,
• connective tissue components in the head, meninges (coverings)
• sympathetic and enteric neurons,
• muscle, connective tissues, and bone of pharyngeal arch origin; 99
102. Neural tube defects:
• are among the most common congenital anomalies.
•Occur when tube closure fails to occur
• rate of neural tube defects decrease with administration of folic acid
400µg daily. 102
103. • Meroencephaly (partial absence of the brain):
– is the most severe neural tube defect
– If neural tube fails close in cranial region
– the most common anomaly affecting the CNS.
• Spina bifida:
– If closure fails anywhere from cervical region caudally.
– Most commonly in the lumbosacral region
103
105. DEVELOPMENT OF SOMITES
paraxial mesoderm
• derived from cells of primitive node.
• appears as a thick, longitudinal column of cells
• Each column is continuous laterally with the intermediate mesoderm.
• differentiates, condenses, and begins to divide into paired cuboidal bodies,
the somites.
lateral mesoderm
• is continuous with the extraembryonic mesoderm covering the umbilical
vesicle and amnion.
• Continous with intermediate mesoderm
• gradually thins into a layer of lateral mesoderm.
105
106. somites (soma= body)
• form in a craniocaudal sequence.
• are blocks of mesoderm located on each side of the developing neural tube.
• About 38 pairs of somites form during the somite period of human development (20 to 30d).
• 42 to 44 pairs are present at end of the fifth week.
• form distinct surface elevations used as one of several criteria for determining an
embryo's age
• give rise to most of the axial skeleton and associated musculature.
• Cranial somites are the oldest and caudal somites are the youngest.
• the first pair arises in the occipital region of the embryo at approximately the 20th
day
106
107. • new somites appear in
craniocaudal sequence at a rate
of approximately 3pairs/day until
42 to 44 pairs are present
• There are:
– 4 occipital,
– 8 cervical,
– 12 thoracic,
– 5 lumbar,
– 5 sacral,
– and 8 to 10 coccygeal pairs.
• The first occipital and the last 5-
7coccygeal somites later
disappear
• the remaining somites form the
axial skeleton 107
109. Somite differentiation
• cells of somite undergo a process of epithelization and
arrange themselves in a donut shape around a small lumen.
• Cells at the dorsomedial and ventrolateral edges of the
somite form precursors for muscle cells.
• cells between these two groups (dorsolateral) form the
dermatome.
• Cells from both muscle precursor groups become
mesenchymal again and migrate beneath the dermatome
to create dermomyotome.
• cells from the ventrolateral edge migrate into the parietal
layer of lateral plate mesoderm to form most of the
musculature for the body wall.
– (external and internal oblique and transversus
abdominis muscles) and most of the limb muscles 109
110. • dermomyotome
• It’s cells ultimately form dermis for the skin of the back and muscles
for the back, body wall (intercostal muscles), and some limb muscles.
• From each somite:
• sclerotome (the tendon cartilage and bone component),
– formed by cells in the ventromedial walls of the somite
those lose their epithelial characteristics, become
mesenchymal (fibroblast-like).
– It will differentiate into the vertebrae and ribs.
• Myotome (providing the segmental muscle
component),
• dermatome, which forms the dermis of the back.
110
112. Intermediate Mesoderm
• Temporarily connects paraxial mesoderm with the lateral
plate
• differentiates into: urogenital structures:
Lateral Plate Mesoderm:- splits into:
• parietal (somatic) : line the intraembryonic cavity
– located beneath the ectodermal epithelium and continuous with
the extraembryonic mesoderm covering the amnion
– together with overlying ectoderm, forms the lateral body wall
folds (somatopleure).
– These folds, together with the head (cephalic) and tail (caudal)
folds, close the ventral body wall.
– forms the dermis of the skin in the body wall and limbs,
the bones and connective tissue of the limbs, and the
sternum. 112
113. – Mesoderm cells of the parietal layer surrounding the
intraembryonic cavity form thin membranes,
• the mesothelial ( serous) membranes line the peritoneal, pleural,
and pericardial cavities.
• visceral (splanchnic) layers: surround the organs,
– located adjacent to the endoderm and continuous with the
extraembryonic mesoderm covering the umbilical vesicle
– Together with embryonic endoderm, forms the wall of the
gut tube (splanchnopleure).
– form a thin serous membrane around each organ
113
114. DEVELOPMENT OF THE INTRAEMBRYONIC COELOM
• embryonic body cavity appears as isolated coelomic
spaces in the lateral mesoderm and cardiogenic (heart-
forming) mesoderm.
• which divides the lateral mesoderm into two layers
• During the second month, the intraembryonic coelom
is divided into three body cavities:
– Pericardial cavity
– Pleural cavities
– Peritoneal cavity
114
115. Blood and Blood Vessels
• arise from mesoderm.
Blood vessels:
• begins in the extraembryonic mesoderm of the umbilical
vesicle, connecting stalk, and chorion.
• Embryonic blood vessels begin to develop approximately 2
days later.
• form in two ways:
– Vasculogenesis:
• arise from blood islands
• formation of new vascular channels
• from assembly of individual cell precursors called angioblasts.
– Angiogenesis:
• new vessels by budding and branching from preexisting vessels.
• blood islands:
– first appear in mesoderm surrounding the wall of the yolk sac at 3
weeks of development and slightly later in lateral plate mesoderm
and other regions.
115
116. – arise from mesoderm cells that are induced to form
hemangioblasts (a common precursor for vessel and blood cell
formation).
– Small cavities appear within the blood islands.
– Angioblasts flatten to form endothelial cells that arrange
themselves around the cavities in the blood island to form
the endothelium.
– These endothelium-lined cavities soon fuse to form
networks of endothelial channels (vasculogenesis).
– Vessels sprout into adjacent areas by endothelial budding
and fuse with other vessels.
• The definitive hematopoietic stem cells are derived from
mesoderm surrounding the aorta
• These cells colonize the liver.
• Angioblasts:
– Are mesoderm derived vessel-forming cells
– aggregate to form cell clusters called blood islands
116
118. Blood cells: (hematogenesis)
• develop from the endothelial cells
• develop on the umbilical vesicle and allantois at the
end of the third week.
• later in specialized sites along the dorsal aorta.
• does not begin in the embryo until the fifth week.
• occurs in various parts of the embryonic
mesenchyme, mainly:
– the liver (the major hematopoietic organ of the embryo
and fetus from 2nd-7th months.), and later in the spleen,
bone marrow, and lymph nodes.
118
119. • heart and great vessels:
– form from mesenchymal cells in the cardiogenic area.
• endocardial heart tubes-
– develop during the third week
– fuse to form a primordial heart tube.
– tubular heart joins with blood vessels in the:
• embryo, connecting stalk, chorion,
• and umbilical vesicle to form a primordial cardiovascular
system.
– heart begins to beat on the 21st or 22nd day.
– cardiovascular system is the first organ system to reach a
functional state.
– embryonic heartbeat can be detected during the fifth
week. 119
122. DEVELOPMENT OF CHORIONIC VILLI
• Primary chorionic villi: appear at the end of the
second week, they begin to branch.
– Consists core cytotrophoblast covered by a syncytial
layer.
• Secondary chorionic villi:
– Early in the third week,
– when mesenchyme grows in primary villi.
– cover the entire surface of the chorionic sac.
– Some mesenchymal cells in the villi soon differentiate
into capillaries and blood cells
• Tertiary chorionic villi: when blood vessels are
visible in secondary villi.
– The capillaries fuse to form arteriocapillary networks,
122
123. • cytotrophoblastic shell: is when cytotrophoblastic
cells of the chorionic villi proliferate and extend
through the syncytiotrophoblast
– which gradually surrounds the chorionic sac and attaches
it to the endometrium.
• stem chorionic villi (anchoring villi): Villi that
attach to the maternal tissues through the
cytotrophoblastic shell.
• Branch chorionic villi (terminal villi): villi that
grow from the sides of the stem villi.
123
126. Organogenetic Period:
• 4th to 8th Weeks
• All major external and internal structures are
established.
• By the end of this period, the main organ systems have
begun to develop; however, the function of most of
them is minimal except for the cardiovascular system.
• embryo has a distinctly human appearance at eighth
week.
• exposure of embryos to teratogens during this period
may cause major congenital anomalies.
• Teratogens:
– are agents such as drugs and viruses
– produce or increase the incidence of congenital anomalies
126
127. FOLDING OF THE EMBRYO
• occurs in both the median and horizontal planes and results from
rapid growth of the embryo.
• Folding at the cranial and caudal ends and sides of the embryo
occurs simultaneously.
Folding in the Median Plane
Head Fold
• the neural folds in the cranial region have thickened to form the
primordium of the brain.
• Later, the developing forebrain grows cranially beyond the
oropharyngeal membrane and overhangs the developing heart.
• Concomitantly, the septum transversum (transverse septum),
primordial heart, pericardial coelom, and oropharyngeal
membrane move onto the ventral surface of the embryo.
• After folding, the septum transversum lies caudal to the heart
where it subsequently develops into the central tendon of the
diaphragm.
127
128. Tail Fold
• results primarily from growth of the distal part of the neural
tube-the primordium of the spinal cord.
• During folding, part of the endodermal germ layer is
incorporated into the embryo as the hindgut (primordium of
descending colon).
• Before folding, the primitive streak lies cranial to the cloacal
membrane; after folding, it lies caudal to it.
lateral folds
• produced by the rapidly growing spinal cord and somites.
• The primordia of the ventrolateral wall fold toward the
median plane.
• As the abdominal walls form, part of the endoderm germ layer
is incorporated into the embryo as the midgut.
• Initially, there is a wide connection between the midgut and
umbilical vesicle however; after lateral folding, the connection
is reduced to an omphaloenteric duct.
128
131. HIGHLIGHTS OF 4th-8th WEEKS
Fourth Week
• Major changes in body form occur during the fourth week.
• at the beginning, the embryo is almost straight
• has 4-12 somites.
24 days:
• the first two pharyngeal arches are visible.
• first (mandibular arch) and the second (hyoid arch) are distinct.
• major part of the first arch gives rise to the mandible (lower jaw), and a
rostral extension of the arch, the maxillary prominence, contributes to the
maxilla (upper jaw).
• embryo become slightly curved because of the head and tail folds.
• heart produces a large ventral prominence and pumps blood.
26 days
• 3 pairs of pharyngeal arches are visible by rostral neuropore is closed.
• Forebrain: produces a prominent elevation of the head
• embryo is C-shaped curvature because of folding.
131
132. • Upper limb buds:
• are recognizable by day 26 or 27
• small swellings on the ventrolateral body walls. 132
135. • otic pits: primordia of the internal ears.
• lens placodes:
– ectodermal thickenings
– indicates the future lenses of the eyes on the sides of the head.
By the end of 4th week (28th day)
• fourth pair of pharyngeal arches and the lower limb buds are
visible.
• a long tail-like caudal eminence is a characteristic feature
• Caudal neuropore is closed
5th week:
• Changes in body form are minor compared with those that
occurred during the 4th week,
• growth of the head exceeds that of other regions because of the
rapid development of the brain and facial prominences.
• Mesonephric ridges indicate the site of the mesonephric kidneys,
which are interim (temporary) excretory organs in humans.
135
136. sixth Week
• Embryos:
– show reflex response to touch.
– show spontaneous movements, such as twitching of the trunk and limbs.
• upper limbs:
– begin to show regional differentiation as the elbows and large
handplates develop .
– digital rays (primordia of the digits): begin to develop in the handplates.
• lower limbs develop 4 to 5 days later than that of the upper limbs.
• Auricular hillocks: develop around the pharyngeal groove or cleft
between the first two pharyngeal arches.
– This groove becomes the external acoustic meatus (external auditory
canal).
– auricular hillocks contribute to the formation of the auricle.
• Retinal pigment has formed, the eye is now obvious.
• Trunk and Neck have begun to straighten.
136
137. • Intestines: enter the proximal part of the umbilical cord.
– Is normal umbilical herniation in the embryo.
– because the abdominal cavity is too small at this age to
accommodate the rapidly growing intestine.
seventh week
• limbs undergo considerable change.
• Notches appear between the digital rays in the
handplates.
• omphaloenteric duct: narrowed communication
between the primordial gut and umbilical vesicle.
• ossification of the bones of the upper limbs has
begun. 137
139. 8th week
At the beginning:
• digits of the hand are separated but noticeably webbed.
• Notches are clearly visible between the digital rays of the feet.
At the end:
– all regions of the limbs are apparent, the digits have
lengthened and are completely separate.
– Purposeful limb movements first occur.
– Ossification begins in the femur.
– All evidence of the caudal eminence has disappeared.
– the embryo has distinct human characteristics
– head is still disproportionately large, constituting almost half
of the embryo.
– The auricles of the external ears begin to assume their final
shape. 139
141. ESTIMATION OF EMBRYONIC AGE
greatest length: embryos of the third and early
fourth weeks are straight.
Crown-rump length: is most frequently used for
older embryos.
Standing height, or crown-heel length: is sometimes
measured for 8-week embryos.
• The length of an embryo is only one criterion for
establishing age.
141
143. The Fetal Period: 9th Week to Birth
• rapid body growth and differentiation of tissues, organs, and
systems.
• relative slowdown in the growth of the head compared with
the rest of the body.
Viability of Fetuses
• is defined as the ability of fetuses to survive in the
extrauterine environment (i.e., after a premature birth).
– < 500 g at birth usually do not survive.
– between 1500 and 2500 g may survive, but complications may
occur;
• There is no sharp limit of development, age, or weight at
which a fetus automatically becomes viable.
ESTIMATION OF FETAL AGE
• Ultrasound measurements of the crown-rump length (CRL).
• Fetal head measurements and femur length
• intrauterine period may be divided into days, weeks, or
months 143
144. • Trimestersof Pregnancy
• gestational period is divided into:
• first trimester: at the end all major systems are
developed
• second trimester: the fetus grows sufficiently in
size.
• third trimester: the fetus may survive if born
prematurely.
– fetus weighs ~2500 g
• each lasting 3 months
REFERENCE POINT DAYS WEEKS
Fertilization* 266 38
LNMP 280 40
144
145. AGE
(WEEKS
)
CR LENGTH
(MM)*
FOOT
LENGTH
(MM)* FETAL WEIGHT (G)MAIN EXTERNAL CHARACTERISTICS
9 50 7 8 - Eyelids closing or closed. Head large and more
rounded.
- External genitalia still not distinguishable as
male or female. Intestines in proximal part of
umbilical cord. Ears are low-set.
10 61 9 14 - Intestines in abdomen. Early fingernail
development.
12 87 14 45 - Sex distinguishable externally.
Well-defined neck.
14 120 20 110 - Head erect. Eyes face anteriorly. Ears are
close to their definitive position. Lower limbs
well developed. Early toenail development.
Criteria for Estimating Fertilization Age during the Fetal Period
145
146. 16 140 27 200 External ears stand out from head.
18 160 33 320- Vernix caseosa covers skin. Quickening (1st
movements) felt by mother.
20 190 39 460 Head and body hair (lanugo) visible. testes have
begun to descend, but they are still located on
the posterior abdominal wall
Viable Fetuses
22 210 45 630 -Skin wrinkled, translucent, and pink to red.
24 230 50 820 -Fingernails present. Lean body.
26 250 55 1000 -Eyelids partially open. Eyelashes present.
28 270 59 1300 -Eyes wide open. Good head of hair often
present. Skin slightly wrinkled.
146
147. 30 280 63 1700 Toenails present. Body filling out. Testes
descending.
32 300 68 2100 Fingernails reach fingertips. Skin
smooth.
36 340 79 2900 -Body usually plump. Lanugo (hairs)
almost absent.
-Toenails reach toe-tips. Flexed limbs;
firm grasp.
38 360 83 3400 -Prominent chest; breasts protrude.
Testes in scrotum or palpable in inguinal
canals. Fingernails extend beyond
fingertips.
• Vernix caseosa: consists of a mixture of dead epidermal cells and a
fatty substance (secretion) from the fetal sebaceous glands.
• protects the delicate fetal skin from abrasions, chapping, and
hardening that result from exposure to the amniotic fluid. 147
148. • EXPECTED DATE OF DELIVERY
• is 266 days or 38 weeks after fertilization or 280 days or 40
weeks after LNMP.
• Approximately 12% of babies are born 1 to 2 weeks after the
expected time of birth.
• Nägele's rule EDD = count back 3 months from the first day
of the LNMP and add a year and 7 days.
• Post maturity Syndrome
- Prolongation of pregnancy for 3 or more weeks beyond the
EDD
- occurs in 5% to 6% of women.
- fetuses have:
- dry skin,
- are often overweight,
- and have no lanugo, decreased or absent vernix caseosa,
- long nails, and increased alertness
148
149. FACTORS INFLUENCING FETAL GROWTH
• Many factors may affect prenatal growth: maternal,
fetal, and environmental.
– Cigarette Smoking
– Multiple Pregnancy
– Alcohol and Illicit Drugs
– Impaired Uteroplacental and Fetoplacental Blood Flow
– Genetic Factors and Growth Retardation
– Severe malnutrition
PROCEDURES FOR ASSESSING FETAL STATUS
• Ultrasonography
– is the primary imaging modality because of its wide
availability, low cost, and lack of known adverse effects.
– Placental and fetal size, multiple births, abnormalities of
placental shape, and abnormal presentations can be
determined.
149
150. Diagnostic Amniocentesis
• performed between 15 and 18 weeks gestation.
• through the mother's anterior abdominal and uterine walls into
the amniotic cavity by piercing the chorion and amnion.
• amniotic fluid is withdrawn.
• 15 to 20 mL can be safely withdrawn.
• is a common technique for detecting genetic disorders (e.g.,
Down syndrome).
• common indications are:
– Advanced maternal age (38 years or older)
– Previous birth of a trisomic child (e.g., Down syndrome)
• Chromosome abnormality in either parent
• Women who are carriers of X-linked recessive disorders (e.g.,
hemophilia)
• History of neural tube defects in the family (e.g., spina bifida
cystica;) 150
152. Alpha-fetoprotein Assay (fetal form of serum albumin.)
• is a glycoprotein
• synthesized in the fetal liver, umbilical vesicle, and gut.
• is found in high concentration in fetal serum.
• Small amounts of AFP normally enter the amniotic
fluid.
Increased AFP in the amniotic fluid with severe anomalies of the
central nervous system and ventral abdominal wall is high.
– Maternal serum AFP concentration
higher than normal when fetus has an open neural tube
defect.
low when the fetus has Down syndrome (trisomy 21),
trisomy 18, or other chromosome defects.
152
153. 20th week
Lanugo and head hair appear,
Skin is coated with vernix caseosa.
Eyelids are closed during most of the fetal period but begin
to reopen at approximately 26 wks.
At this time, the fetus is usually capable of extrauterine
existence, mainly because of the maturity of its respiratory
system.
• Until ~ 30 wks, the fetus appears reddish because of the
thinness of its skin and the relative absence of subcutaneous
fat.
• Fat usually develops rapidly during the last 6 to 8 weeks,
giving the fetus a smooth, plump appearance.
153
154. Chorionic Villus Sampling (CVS)
• Biopsies of trophoblastic tissue (5-20 mg)
• obtained by inserting a needle, guided by ultrasonography, through the
mother's abdominal and uterine walls (transabdominal) into the
uterine cavity.
• is also performed transcervically by passing a polyethylene catheter
through the cervix and guided by real-time ultrasonography.
• The risk of miscarriage with CVS is approximately 1%, more than
with amniocentesis.
• sample are used for detecting chromosomal abnormalities, inborn
errors of metabolism, and X-linked disorders.
• can be performed between 10 and 12 weeks of gestation.
• major advantage of CVS over amniocentesis is that it allows the
results of chromosomal analysis to be performed several weeks earlier
than when performed by amniocentesis.
154
155. Sex Chromatin Patterns
• Fetal sex can be determined
by noting the presence or
absence of sex chromatin in
the nuclei of cells
recovered from amniotic
fluid.
• Females with three X
chromosomes (46, XXX)
have two masses of sex
chromatin.
155
156. Fetoscopy
• Using fiberoptic (fetoscope) lighting instruments, parts of the fetal body may
be directly observed.
• It is possible to scan the entire fetus looking for congenital anomalies such
as cleft lip and limb defects.
• Fetoscope is usually introduced in similar way in which the needle is
inserted during amniocentesis.
• is usually carried out at 17 to 20 weeks of gestation
• Because of the risk to the fetus now has few indications for routine prenatal
diagnosis or treatment of the fetus.
Percutaneous Umbilical Cord Blood Sampling (PUBS) (cordocentesis)
• Performed:
– To obtain fetal blood samples directly from the umbilical vein for the diagnosis
of many fetal conditions, including aneuploidy, fetal growth restriction, fetal
infection, and fetal anemia.
– is usually after 18 weeks of gestation under continuous direct ultrasound
guidance.
• the procedure may be used in treating the fetus directly, including the
transfusion.
156
157. PLACENTA
is the primary site of nutrient and gas exchange between the
mother and fetus.
Is a fetomaternal organ that has two components:
– Fetal part: develops from the chorionic sac
– Maternal part: derived from the endometrium
• functions and activities:
– protection, nutrition, respiration,
– excretion, and hormone production.
157
158. Decidua
Is gravid endometrium.
three regions of the decidua are named according to their
relation to the implantation site :
a. Decidua basalis: is deep to the conceptus that forms the
maternal part of the placenta.
b. Decidua capsularis: is the superficial part overlying the
conceptus.
• As the conceptus enlarges, the decidua capsularis bulges into
the uterine cavity then contacts and fuses with the decidua
parietalis, thereby slowly obliterating the uterine cavity.
• By 22 to 24 weeks, it degenerate due to reduced blood supply
c. Decidua parietalis: is all the remaining parts of the
decidua.
158
159. • decidual reaction: is
cellular and vascular
changes occurring in the
endometrium as the
blastocyst implants
159
160. –Decidual cells: form as cells of the decidua enlarge
• Cells enlarge as glycogen and lipid accumulate in their
cytoplasm in response to increasing progesterone levels
• Many of them degenerate near the chorionic sac in the region of
the syncytiotrophoblast.
May protect the maternal tissue against uncontrolled invasion
by the syncytiotrophoblast and
that they may be involved in hormone production.
Development of the Placenta
– It’s growth in the size and thickness continues rapidly until
the fetus is approximately 18 weeks old (20 weeks'
gestation).
– fully developed placenta covers 15% to 30% of the decidua
and weighs approximately one sixth that of the fetus
160
161. Has two parts:
• Fetal part:
– is formed by the villous chorion.
– project into the intervillous space containing maternal blood.
– villous chorion: develop from Chorionic villi associated with the
decidua basalis.
– villi associated with the decidua capsularis are compressed,
reducing the blood supply to them soon degenerate
producing a relatively avascular bare area, the smooth chorion.
– Smooth chorion fuses with the decidua parietalis, because decidua
capsularis degenerate.
• Maternal part:
– is formed by the decidua basalis.
– By the end of the fourth month, the decidua basalis is almost
entirely replaced by the fetal part of the placenta.
• shape of the placenta is determined by the persistent area of
chorionic villi. 161
164. • Intervillous space of the placenta:
– contains maternal blood, contains approximately 150 mL
of blood
– derived from coalescence of the lacunae that developed
in the syncytiotrophoblast.
– is divided into compartments by the placental septa;
– But there is free communication between the
compartments because the septa do not reach the
chorionic plate.
– Blood in space:
• carries oxygen and nutritional materials
• also contains fetal waste products such as carbon dioxide, salts,
and products of protein metabolism.
• from the spiral endometrial arteries in the decidua basalis
• drained by endometrial veins
164
166. Placental septa:
– wedge-shaped areas of decidua
– project toward the chorionic plate (the part of the
chorionic wall related to the placenta).
– divide the fetal part of the placenta into irregular convex
areas-cotyledons
– Each cotyledon consists of two or more stem villi and
their many branch villi
Placental Circulation
• Is main exchange of material between the mother and fetus.
• Consist circulations of the fetus and the mother.
• Separated by the placental membrane consisting of
extrafetal tissues.
166
167. Fetal Placental Circulation
Poorly oxygenated blood:
– leaves the fetus and passes through the umbilical arteries to
the placenta.
– form an extensive arteriocapillary-venous system within the
chorionic villi
• arteriocapillary-venous system:
– brings the fetal blood extremely close to the maternal blood.
– provides a very large surface area for the exchange of
metabolic and gaseous products between the maternal and
fetal bloodstreams.
– normally no intermingling of fetal and maternal blood;
however, very small amounts of fetal blood may enter the
maternal circulation when minute defects develop in the
placental membrane. 167
168. Well-oxygenated blood:
– fetal capillaries = thin-walled veins that follow the chorionic arteries
=converge to form the umbilical vein.
Maternal Placental Circulation
• maternal blood:
– in the intervillous space is temporarily outside the maternal circulatory
system.
– through 80 to 100 spiral endometrial arteries in the decidua basalis.
– The blood eventually returns through the endometrial veins to the
maternal circulation.
– is replenished three or four times per minute.
Placental Membrane
• is a composite structure that consists of the extrafetal tissues
• separate the maternal and fetal blood.
• Consists four layers until approximately 20 weeks:
– syncytiotrophoblast, cytotrophoblast,
– connective tissue of villus, and endothelium of fetal capillaries.
168
169. • After the 20th week: consists of three layers
– Because of cytotrophoblastic cells disappear over large areas of the villi
– acts as a barrier only when the molecule is of a certain size,
configuration, and charge such as heparin and bacteria.
Functions of the Placenta
• Has three main functions:
i. Metabolism (e.g., synthesis of glycogen): synthesizes glycogen,
cholesterol, and fatty acids.
ii. Transport of gases and nutrients: between the fetal and maternal
blood
iii. Endocrine secretion (e.g. human chorionic gonadotropin (hCG)
• protein hormones synthesized by the placenta are:
– hCG : similar to luteinizing hormone
– Human chorionic somatomammotropin or human placental
lactogen
– Human chorionic thyrotropin
– Human chorionic corticotropin
169
171. Placental Transfer
Transfer of Gases
Nutritional Substances
Hormones
Electrolytes
Maternal Antibodies: IgG gamma globulins are readily
transported to the fetus by transcytosis
Waste Products
Drugs and Drug Metabolites
Infectious Agents: Cytomegalovirus, rubella, and
coxsackie viruses, and viruses associated with variola,
varicella, measles, and poliomyelitis may pass through
the placental membrane and cause fetal infection.
171
172. PARTURITION (childbirth)
Process during which the fetus, placenta, and fetal
membranes are expelled from the mother's reproductive
tract.
Labor: is the sequence of involuntary uterine contractions.
– factors that trigger labor are not completely understood
– but several hormones are related to the initiation of
contractions.
• fetal hypothalamus corticotropin-releasing
hormone=anterior hypophysis (pituitary)
adrenocorticotropin=corticol from the suprarenal
(adrenal) cortex= involved in the synthesis of
estrogensstimulate uterine contraction.
• Oxytocin: elicit peristaltic contractions of uterine
smooth muscle 172
173. • Clinically divided into three stages:
1. Dilation: begins with progressive dilation of the cervix
– ends when the cervix is completely dilated.
– regular painful contractions of the uterus occur less than 10
minutes apart.
– average duration: ~12 hours for primigravidas and ~7 hrs for
multigravidas.
2. Expulsion: from cervix is fully dilated to delivery of the
baby.
– fetus descends through the cervix and vagina.
– average duration: is 50 minutes for primigravidas and 20
minutes for multigravidas.
3. Placental stage: soon after baby is born to expulsion
of the placenta and membranes.
– duration is 15 minutes in ~90% of pregnancies
173
176. • Placental Abnormalities
• Placenta accreta: abnormal adherence of chorionic villi to
the myometrium.
• placenta percreta: When chorionic villi penetrate the full
thickness of the myometrium to or through the perimetrium
(peritoneal covering).
• placenta previa: when the blastocyst implants close to or
overlying the internal os of the uterus. 176
178. Umbilical Cord
• attached to the placenta usually near the center of the fetal
surface of this organ, but it may attach at any point.
• is usually 1 to 2 cm in diameter and 30 to 90 cm in length
(average, 55 cm).
• Excessively long or short cords are uncommon.
• has two arteries and one vein that are surrounded by mucoid
connective tissue (Wharton jelly).
• Because the umbilical vessels are longer than the cord, twisting
and bending of the vessels are common.
Amnion and Amniotic Fluid
• Amnion:
– thin but tough forms a fluid-filled, membranous amniotic sac
that surrounds the embryo and fetus.
– As it enlarges, it gradually obliterates the chorionic cavity and
forms the epithelial covering of the umbilical cord. 178
180. Amniotic Fluid
• Plays a major role in fetal growth and development.
• Initially:
– some amniotic fluid is secreted by amniotic cells;
– most is derived from maternal tissue and interstitial fluid by
diffusion.
– Before keratinization of the skin occurs, a major pathway for
passage of water and solutes in tissue fluid from the fetus to
the amniotic cavity.
– Fluid is also secreted by the fetal respiratory and
gastrointestinal tracts.
– respiratory tract 300 to 400 mL/day.
– ~11th week, : excreting urine into the amniotic cavity.
– volume of amniotic fluid normally increases slowly,
– ~30 mL at 10 weeks, 350 mL at 20 weeks, and 700 to 1000
mL by 37 weeks. 180
181. Circulation of Amniotic Fluid
• water content changes every 3 hours.
• Large amounts of water pass through the
amniochorionic membrane into the maternal tissue fluid
and enter the uterine capillaries.
• Amniotic fluid:
– is swallowed by the fetus absorbed by the fetus's
respiratory and digestive tracts.
– fetus swallows up to 400 mL of amniotic fluid/day=passes
into the fetal bloodstream and the waste products in it cross
the placental membrane and enter the maternal blood in the
intervillous space.
– Excess water in the fetal blood is excreted by the fetal
kidneys and returned to the amniotic sac through the fetal
urinary tract.
181
182. Disorders of Amniotic Fluid Volume
Oligohydramnios: Low volumes of amniotic fluid for
any particular gestational age
– Causes: diminished placental blood flow.
• Preterm rupture of the amniochorionic membrane.
• renal agenesis (failure of kidney formation).
• obstructive uropathy (urinary tract obstruction).
Complications:
• pulmonary hypoplasia, facial defects, and limb defects because of
fetal compression by the uterine wall.
Polyhydramnios: High volumes of amniotic fluid
– result when the fetus does not swallow the usual amount.
– Cause:
• Most cases (60%) are idiopathic (unknown cause),
• 20% are caused by maternal factors,
• 20% are fetal in origin e.g esophageal atresia (blockage). 182
183. A fetus with the
amniotic band
syndrome showing
amniotic bands
constricting the left arm.
B, Drawing indicating
the structures shown in
A.
183
184. Significance of Amniotic Fluid
1. The buoyant amniotic fluid Permits symmetric external
growth of the embryo and fetus
2. Acts as a barrier to infection
3. Permits normal fetal lung development
4. Prevents adherence of the amnion to the embryo and fetus
5. Cushions the embryo and fetus against injuries by
distributing impacts the mother receives
6. Helps control the embryo's body temperature by
maintaining a relatively constant temperature
7. Enables the fetus to move freely, thereby aiding muscular
development in the limbs, for example Assists in
maintaining homeostasis of fluid and electrolytes
184
185. Premature Rupture of Fetal Membranes
• Rupture of the amniochorionic membrane:
– is the most common event
– leads to premature labor and delivery
– resulting in oligohydramnios.
– Loss of amniotic fluid removes the major protection that the fetus
has against infection.
THE UMBILICAL VESICLE (YOLK SAC)
• By 10 weeks, the umbilical vesicle has shrunk to a pear-
shaped remnant approximately 5 mm in diameter
• is connected to the midgut by a narrow omphaloenteric duct
(yolk stalk).
• By 20 weeks, the umbilical vesicle is very small; thereafter, it
is usually not visible.
• is recognizable in ultrasound examinations until the end of the
first trimester.
185
186. Significance of the Umbilical Vesicle
is nonfunctional as far as yolk storage is concerned (hence
the name change
It has a role in the transfer of nutrients to the embryo during
the 2nd
and 3rd
weeks when the uteroplacental circulation is
being established.
Blood development first occurs in it’s wall (in the 3rd
week)
and continues until it begins in the liver (6th
week).
In the 4th
week, it’s endoderm (derived from epiblast) is
incorporated into the embryo as the primordial gut, gives
rise to the epithelium of the trachea, bronchi, lungs, and
digestive tract.
Primordial germ cells appear in the endodermal lining of it’s
wall (3rd
week). 186
188. MULTIPLE PREGNANCIES
Twins and Fetal Membranes
• Twins can be:
– dizygotic (DZ) (fraternal) twins: that originate from two
zygotes,
• two thirds of twins
• It’s frequency shows marked racial differences
– being approximately 1 in 500 in Asians, 1 in 125 in whites, and
as high as 1 in 20 in some African populations.
• increases with maternal age.
• may be of the same sex or different sexes.
• are no more alike genetically than brothers or sisters born at
different times.
• The only thing they have in common is that they were in
their mother's uterus at the same time.
• always have two amnions and two chorions, but the
chorions and placentas may be fused.
188
190. Monozygotic (MZ) (identical) twins: that originate
from one zygote.
• the type of placenta and membranes formed depends
on when the twinning process occurs
• approximately the same in all populations.
• are of the same sex, genetically identical, and very
similar in physical appearance.
• Physical differences maybe environmentally induced,
e.g., because of anastomosis of placental vessels.
Anastomosis of Placental Blood Vessels
• between blood vessels of fused placentas of DZ twins may
result in erythrocyte mosaicism.
• The members of these DZ twins have red blood cells of two
different types 190
192. Twin Transfusion Syndrome
• occurs in as many as 30% of monochorionic-diamniotic MZ
twins.
• is shunting of arterial blood from one twin through
arteriovenous anastomoses into the venous circulation of the
other twin.
• The donor twin is small, pale, and anemic, whereas the
recipient twin is large and polycythemic, an increase above
the normal in the number of red blood cells.
• In lethal cases, death results from anemia in the donor twin
and congestive heart failure in the recipient twin.
192
193. Frequency of Types of Placentas and Fetal
Membranes in Monozygotic (MZ) and Dizygotic
(DZ) Twins
ZYGOSITY
SINGLE
CHORION
SINGLE
AMNION
TWO
AMNIONS
TWO CHORIONS
FUSED
PLACENTAS*
TWO
PLACENTAS
MZ Very rare 65% 25% 10%
DZ - - 40% 60%
193
194. Conjoined Monozygotic Twins
• When embryonic disc does not divide completely, or
adjacent embryonic discs fuse.
• is 1 in 50,000 to 100,000 births.
• are connected to each other by skin only or by
cutaneous and other tissues
• (Gr., pagos: fixed) twins are named according to the
regions that are attached,
– e.g., thoracopagus: anterior union of the thoracic regions.
Superfecundation
• is the fertilization of two or more oocytes at different
times.
• Rare in humans
• DZ human twins with different fathers have been
confirmed by genetic markers.
194
196. Conjoined twins before separation
Conjoined twins after
separation
(4yrs)
• Triplets may be derived from:
• One zygote and be identical
• Two zygotes and consist of identical twins and a
singleton
• Three zygotes and be of the same sex or of different
sexes
196
197. Body Cavities, Mesenteries, and Diaphragm
Intraembryonic coelom: appears early in the 4th week.
– Its curve or bend at the cranial end of the embryo
represents the future pericardial cavity,
– and its limbs (lateral extensions) indicate the future
pleural and peritoneal cavities.
• is continuous with the extraembryonic coelom at the lateral
edges of the embryonic disc.
• The communication is important because is the way through
umbilical herniation of gut occurs.
• are brought together on the ventral aspect of the embryo during
embryonic folding in the horizontal plane soon ventral
mesentery degenerates resulting in a large embryonic
peritoneal cavity extending from the heart to the pelvic region.
197
198. Sketch of a lateral view of an
embryo (approximately 33 days).
The rectangle indicates the area
enlarged in B. The primordial body
cavities are viewed from the left
side after removal of the lateral
body wall. C, Transverse section
through the embryo at the level
shown in B.
198
199. THE EMBRYONIC BODY CAVITY
• Develop from intraembryonic coelom
• is divided into three well-defined cavities during the fourth
week:
– A pericardial cavity
– Two pericardioperitoneal canals
– A peritoneal cavity
• peritoneal cavity
– the major part of intraembryonic coelom
– is connected with the extraembryonic coelom at the umbilicus
– loses its connection with the extraembryonic coelom during the 10th
week as the intestines return to the abdomen from the umbilical cord.
– have a:
• parietal wall: lined by mesothelium (future parietal layer of
peritoneum)
– derived from somatic mesoderm
• visceral wall: covered by mesothelium (future visceral layer
of peritoneum)
– derived from splanchnic mesoderm.
199
200. Drawing of a dorsal view of a 22-day embryo showing the outline of the horseshoe-shaped
intraembryonic coelom. The amnion has been removed, and the coelom is shown as if the embryo
were translucent. The continuity of the intraembryonic coelom, as well as the communication of
its right and left limbs with the extraembryonic coelom, is indicated by arrows. B, Transverse
section through the embryo at the level shown in A.
200
201. • During formation of the head fold:
– the heart and pericardial cavity are relocated
ventrocaudally, anterior to the foregut.
– As a result, the pericardial cavity opens into
pericardioperitoneal canals, which pass dorsal to the
foregut.
• Mesenteries
– is a double layer of peritoneum that begins as an
extension of the visceral peritoneum covering an organ.
– the dorsal and ventral mesenteries divide the peritoneal
cavity into right and left halves.
– ventral mesentery soon disappears, except where it is
attached to the caudal part of the foregut (primordium of
stomach and proximal part of duodenum). 201
202. A, Lateral view of an embryo (approximately 26 days). B, Schematic sagittal section. C, Transverse
section at the level shown in A.
D, Lateral view of an embryo (. F, Transverse section as indicated in D,.
202
203. Division of the Embryonic Body Cavity
• Septum transversum:- a thick plate of mesodermal
tissue that occupies the space between the thoracic
cavity and omphaloenteric duct.
– is the primordium of the central tendon of the diaphragm.
• Pericardioperitoneal canal: each lies lateral to the
proximal part of the foregut (future esophagus) and
dorsal to the septum transversum.
– Partitions form in each that separate the pericardial cavity
from the pleural cavities and the pleural cavities from the
peritoneal cavity.
– Because of the growth of the bronchial buds into it, a pair of
membranous ridges is produced in the lateral wall of each
canal:
• pleuropericardial folds: are located superior to the developing lungs.
• pleuroperitoneal folds: are located inferior to the lungs.
203
204. Illustrations of the
mesenteries and
body cavities at the
beginning of the
fifth week. A,
Schematic sagittal
section.
B to E, Transverse
sections through the
embryo at the
levels indicated in
A. 204
205. drawings of an embryo
(approximately 24
days). A, The lateral
wall of the pericardial
cavity has been
removed to show the
primordial heart. B,
Transverse section of
the embryo illustrates
the relationship of the
pericardioperitoneal
canals to the septum
transversum . C, Lateral
view of the embryo with
the heart removed. D,
Sketch showing the
pericardioperitoneal
canals arising from the
dorsal wall of the
pericardial cavity and
passing on each side of
the foregut to join the
peritoneal cavity.
205
206. Pleuropericardial Membranes
• Form from as the pleuropericardial folds enlarge and fuse with
mesenchyme anterior to esophagus.
• contain the common cardinal veins.
• Initially the bronchial buds are small relative to the heart and
pericardial cavity soon grow laterally into the
pericardioperitoneal canals (future pleural canals).
• As the primordial pleural cavities expand ventrally around the
heart, they extend into the body wall, splitting the
mesenchyme into:
– An outer layer that becomes the thoracic wall
– An inner layer (pleuropericardial membrane) that becomes the
fibrous pericardium.
• The pleuropericardial membranes project into the cranial ends
of the pericardioperitoneal canals By the 7th week fuse with
the mesenchyme ventral to the esophagus, separating the
pericardial cavity from the pleural cavities. 206
208. Pleuroperitoneal Membranes
• As the pleuroperitoneal folds enlarge, they project into
the pericardioperitoneal canals gradually the folds
become membranous, forming the pleuroperitoneal
membranes.
• separate the pleural cavities from the peritoneal cavity.
• are produced as the developing lungs and pleural
cavities expand and invade the body wall are
attached dorsolaterally to the abdominal wall and
initially their crescentic free edges project into the
caudal ends of the pericardioperitoneal canals.
• By 6th week, it extend ventromedially until their free
edges fuse with the dorsal mesentery of the esophagus
and septum transversum. 208
209. DEVELOPMENT OF THE DIAPHRAGM
• develops from four embryonic components:
– Septum transversum
– Pleuroperitoneal membranes
– Dorsal mesentery of esophagus
– Muscular ingrowth from lateral body walls
Septum Transversum
• composed of mesodermal tissue, is the primordium of the
central tendon of the diaphragm.
• grows dorsally from the ventrolateral body wall and forms a
semicircular shelf, which separates the heart from the liver.
• first identifiable at the end of the 3rd week as a mass of
mesodermal tissue cranial to the pericardial cavity.
• After the head folds ventrally during the 4th week, forms a
thick incomplete partition between the pericardial and
abdominal cavities 209
210. Pleuroperitoneal Membranes
• Although it forms large portions of the early fetal
diaphragm, they represent relatively small portions of
the newborn's diaphragm.
Dorsal Mesentery of the Esophagus
• constitutes the median portion of the diaphragm.
• The crura of the diaphragm develop from myoblasts
that grow into the dorsal mesentery of the esophagus.
Positional Changes and Innervation of the Diaphragm
• By 4th week before relocation of the heart, the septum
transversum lies opposite the 3rd-5th cervical somites.
• By 5th week, myoblasts from these somites migrate into
the developing diaphragm, also bringing their nerve
fibers with them. 210
211. A, Sketch of a lateral view of an embryo at the
end of the fifth week (actual size) indicating
the level of sections in B to D. B to E
Transverse section. B, unfused
pleuroperitoneal membranes. C, fused
pleuroperitoneal membranes. D, ingrowth of
the fourth diaphragmatic component from the
body wall.
211
212. A, Approximately 24 days. The septum transversum is at the level of the 3rd-5th cervical
segments. B, Approximately 41 days. C, Approximately 52 days.
• By 6th week, the developing diaphragm is at the level of the
thoracic somites.
• By the beginning of the 8th week, the dorsal part of the
diaphragm lies at the level of the first lumbar vertebra.
• The phrenic nerves in the embryo enter the diaphragm by
passing through the pleuropericardial membranes that mean
subsequently lie on the fibrous pericardium.
212
213. Posterolateral Defects of Diaphragm: once in 2200 newborn
• is the only relatively common congenital anomaly of the
diaphragm
• is associated with congenital diaphragmatic hernia-(CDH,
herniation of abdominal contents into the thoracic cavity).
• CDH may cause inhibition of development (most common cause of
pulmonary hypoplasia) and inflation of lungs .
• Moreover, fetal lung maturation may be delayed.
• CDH, usually unilateral,
– results from defective formation and/or fusion of the pleuroperitoneal
membrane with the other three parts of the diaphragm.
– This results in a large opening in the posterolateral region of the
diaphragm so the peritoneal and pleural cavities are continuous
– Prenatal diagnosis depends on ultrasound examination and magnetic
resonance imaging of abdominal organs in the thorax.
– occurs on the left side in 85% to 90% of cases.
– Because the abdominal organs are most often in the left side of the
thorax, the heart and mediastinum are usually displaced to the right.
– With this condition the lungs are often hypoplastic and greatly reduced in
size. 213
215. Diaphragmatic hernia on left side showing
herniation of liver (A), stomach, and bowel (B),
underneath the liver into left chest cavity. C.
Chest radiograph of a newborn infant showing
herniation of intestinal loops (I) into the left
side of the chest. Note that the heart (H) is
displaced to the right and that the stomach (S)
is on the left side of the upper abdominal
cavity.
215