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EMBRYOLOGY

Regina C. Talavera MD
Embryology

 study of the embryonic and fetal


development of humans (prenatal pd)
 Goal – to understand the principles of
embryogenesis in relation to the
diagnosis, care and prevention of birth
defects
Mitosis
 process whereby a somatic cell divides to
form 2 daughter cells identical to each other
& to the parent cell
 human somatic cells contain 23 pairs
(diploid) of chromosomes = 22 pairs of
autosomes + 1 pair of sex chromosome (XX
or XY)
 each chromosome replicates its DNA and
distributes equal genetic materials between
the daughter cells
Phases of Mitosis

1. Prophase
2. Prometaphase
3. Metaphase
4. Anaphase
5. Telophase
Mitosis - Prophase
 chromosomes begin
to coil, contract and
condense 
becoming shorter
and thicker
 each consists of 2
chromatids, which
are joined at the
centromere
Mitosis - Prometaphase

 chromatids become
distinguishable
Mitosis - Metaphase

 chromosomes line
up in the equatorial
plane
 each attached by
mitotic spindles or
microtubules
Mitosis - Anaphase

 centromeres of
each chromosome
divide
 migration of the
chromatids to
opposite poles of
the spindle
Mitosis - Telophase

 chromosomes
uncoil and lengthen
 nuclear envelope
reforms
 division of the
cytoplasm
Mitosis

 each daughter cells


received ½ of all
the double-
chromosome
material
Meiosis

 process of cell division undergone by


the haploid chromosomes of the male
and female germ cells
 replication of DNA also occurs
 2 phases – 1st and 2nd meiotic division
Meiosis - Purpose

1. To reduce the # of chromosomes


from diploid (46) to haploid (23)
2. To alter the shape of the germ cells in
preparation for fertilization
3. To provide genetic variability through
the process of crossover and random
distribution of homologous
chromosomes to the daughter cells
Meiosis – 1st Division
 Pairing or
synapsis of
homologous
chromosome
(bivalents)
 1st characteristic
feature of meiosis
 each consists of 4
chromatids
Meiosis – 1st Division
 Crossover
 interchange of
chromatid segments
between bivalents
 chiasm formation
 2nd characteristic
feature of meiosis
 blocks of genes are
exchanged
Meiosis – 1st Division

 Anaphase
 each daughter cell
contains 1 member
of the chromosome
pair
Meiosis – 2nd Division
• noDNA synthesis
occurs prior to this
stage
• the 23 double-
stranded chromosomes
divide at the
centromere and each
receives 23 chromatids
Meiosis – Result

 1 primary oocyte
gives rise to 4
daughter cells = 1
mature oocyte + 3
polar bodies
 22 + 1X
chromosome
Meiosis – Result
 primary spermatocyte
gives rise to 4
daughter cells which
develop into 4 mature
gametes
 2 = 22 + 1X
chromosome
 2 = 22 + 1Y
chromosome
Clinical Correlates

1. Meiotic Nondisjunction
 no separation occurs
 1 cell receives 24 chromosomes and the
other 22
 At fertilization, normal gamete of 23 fuses
with abnormal gamete producing either
monosomy 45 or
trisomy 47
Clinical Correlates

2. Mitotic Nondisjunction
 involves chromosome 21 (Down
Syndrome)
 Mosaicism – few or many
characteristics of Down Syndrome
depending on the # of cells involved
Clinical Correlates

3. Balanced Translocation
 breakage and reunion of chromosomes
between 2 chromosomes
 no critical genetic material is lost

 normal individual

4. Unbalanced Translocation
 part of 1 chromosome is lost

 produces an altered phenotype


Clinical Correlates

5. Partial Trisomy or Monosomy


 breaks occur but pieces do not attach to
other chromosomes
 eg Cri-du-chat = (5p) Syndrome

 Increasing maternal and paternal age 


gene mutation  aberrant phenotypes
 Many major chromosomal abnormalities
result in spontaneous abortion
Primordial Germ Cells
 direct descendants of mature male and
female germ cells or gametes
 seen in embryos in the wall of the yolk sac
at the end of the 3rd week of development
 migrate by ameboid movement toward the
developing gonads (primitive sex glands)
and arrive between the 4th and 5th week of
development
Spermatogenesis

 process wherein the male germ cell


develops into maturity
 process takes approximately 64 days
 differentiation of primordial germ cells
begins at puberty
Spermatogenesis
Male germ cells
( at birth, found in the sex cords of testes)

Spermatogonia
(shortly before puberty, sex cords acquire a lumen=
seminiferous tubules)

Type A Type B

-divide by mitosis mitosis


-provide a continuous
reserve of stem cell
Primary Spermatocyte
(prolonged prophase
of 22 days)
Spermatogenesis

Primary Spermatocyte

meiosis I

Secondary Spermatocyte

meiosis II

Spermatid (haploid)

spermiogenesis

Spermatozoa
Spermiogenesis
 series of changes
resulting in the
transformation of
spermatids into
spermatozoa
1. Formation of the
acrosome
2. Condensation of the
nucleus
3. Formation of neck, middle
piece and tail
4. Shedding of most of the
cytoplasm
Oogenesis
 process wherein the female germ cell
develops into maturity
 Each ovarian cycle produces a # of follicles
but only 1 develops into maturity, the others
degenerate and become atretic.
 2nd meiotic division completed only if
fertilization takes place, otherwise,
degeneration occurs approximately 24 hours
after ovulation
 Ovulation – secondary oocyte in metaphase
Oogenesis – Prenatal Maturation
Female Primordial Germ Cell

Oogonia

mitosis

Follicular Cells

mitosis

Primary Oocyte

meiosis

Primordial Follicle
Oogenesis – Postnatal Maturation
Primary Oocyte
-near time of birth = 700T-2M
-starts prophase of the 1st meiotic division

Diplotene or Resting Stage


-instead of metaphase; until before puberty = 400T
-due to oocyte maturation inhibitor, secreted by the follicular cells

5-15 primordial follicles begin to mature with each ovarian cycle

Primary Follicle
Oogenesis – Postnatal Maturation
Primary Follicle
(theca folliculi, zona pellucida)

Secondary Follicle
(antrum, cumulus oopherus)

Tertiary Follicle
= Vesicular or Graaffian Follicle

meiosis I

Secondary Oocyte
+ 1 Polar Body
Ovarian Cycle

= sexual cycle
 regular monthly cycles of females at
puberty
 controlled by the hypothalamus
(gonadotropin-releasing hormone) 
anterior pituitary gland (gonadotropins
= LH and FSH) stimulate and control
the cyclic changes in the ovary
Estrogen

 produced by follicular and thecal cells


 action –
1. causes the uterine endometrium to
enter the follicular or proliferative phase
2. stimulates the pituitary gland to secrete
LH (surge is needed for final stages of
follicular maturation and induce
ovulation)
Ovulation
 process where the
oocyte, together with
surrounding granulosa
cells, form the region of
the cumulus oophorus,
breaks free and floats
out of the ovary
 3o follicle or graafian
follicle increases in size
due to LH and FSH
 1o oocyte in the
diplotene or resting
stage resumes and
finishes its 1st meiotic
division
Ovulation

Stigma
- an avascular spot at the apex of the ovary
- point of rupture of the oocyte during
ovulation
- due to:

1. local weakening and degeneration of the


ovarian surface
2. increase intrafollicular pressure
3. muscular contraction of the ovarian wall
Ovulation

Corona radiata – formed by the


rearrangement of some of the cumulus
oophorus cells around the zona pellucida

Signs of Ovulation:
1. Middle pain or Mittlesmerz
2. Rise in basal body temperature
3. Thinning of the cervical mucus
Ovulation

Failure to Ovulate – due to decrease


concentration of gonadotropins

given drugs that stimulate gonadotropin


release (clomiphene citrate = Clomid)

may produce multiple ovulations, thus, 10x


higher risk for multiple pregnancies
Corpus Luteum
 granulosa cells
remaining in the wall of
the ruptured follicle,
together with cells from
the theca interna
 become vascularized by
surrounding vessels due
to LH
 develop yellow pigment
and become luteal cells
 secretes progesterone
Oocyte Transport
 oocyte surrounded by granulosa cells is
carried into the fallopian tube by:
– the sweeping movements of the
fimbrae
– motion of cilia in the epithelial lining
 rate of transport affected by endocrine
status during and after ovulation (approx.
3-4 days)
Corpus Albicans

 a mass of fibrotic scar tissues formed


by the degeneration of the corpus
luteum if fertilization fail to occur
 associated with decrease
progesterone, thus, precipitating the
menstrual cycle
Menstrual Cycle
 layers or linings of the uterus
– endometrium
– myometrium
– perimetrium
 from puberty (11-13 y/o) until menopause
(45-50 y/o), the endometrium undergoes
cyclic changes approx. every 28 days
 influenced by hormonal control of the ovary
(estrogen and progesterone
3 Phases of the Menstrual Cycle

1. Follicular or Proliferative Phase


- growth of ovarian follicle
- estrogen
2. Secretory or Progestational Phase
- 2-3 days after ovulation
- preparing for fertilization
- progesterone from corpus luteum
3. Menstrual Phase
- shedding of the endometrium (spongy and compact
layers)
- retaining the basal layer, which is the regenerating
layer responsible in rebuilding the glands and arteries
during the proliferative phase
(4. Gravid Phase – implantation of the embryo)
Corpus Luteum of Pregnancy
or Graviditatis
 maintained if fertilization occurs
 degeneration is prevented by human chorionic
gonadotropin hormone (hCG) – secreted by the
trophoblast of the embryo
 secretes progesterone until the 4th month of
development
 slowly regresses as progesterone secretion by
the trophoblastic component of the placenta
becomes adequate to maintain pregnancy
(<----> abortion)
Fertilization
 beginning of the development of a human being
 process wherein the male and female gametes
unite to give rise to a zygote
 site – ampullary region of the uterine tube
Fertilization

 sperm and oocyte remain viable for


approx. 24 hours
 ascent of the sperm from the vagina
to the uterus until the fallopian tube is
caused by the contraction of the
musculature of the uterus and tubes
Fertilization
Sperm undergoes 2 processes:

A. Capacitation (approx. 7 hours)


- period of conditioning in the female reproductive
tract
- glycoprotein coat and seminal plasma proteins are
removed from the plasma membrane that covers the
acrosomal region

B. Acrosome Reaction
- occurs after binding of the sperm to the zona
pellucida of the oocyte
- induced by the zona proteins
- culminates in the release of lysosomal enzymes
(including acrosin and trypsin-like subs.) needed in the
penetration of the zona pellucida (zona reaction)
Phases of Fertilization

Phase I
Penetration of the Corona Radiata

- 200M-300M sperms deposited into the


vagina
- only 300-500 reach the ampulla
- only 1 capacitated sperm is needed for
fertilization and the others aid in the
penetrating of the barriers
Phases of Fertilization

Phase II
Penetration of the Zona Pellucida

- a glycoprotein shell surrounding the egg


- facilitates and maintains sperm binding
- induces the acrosome reaction through the
lysosomal enzymes
Phases of Fertilization

Phase III
Fusion of the Oocyte and Sperm Cell
Membrane

- accomplished between the oocyte membrane


and the membrane that covers the posterior
region of the sperm head
- both head and tail of the sperm enters the
cytoplasm while the plasma membrane is left
behind on the oocyte surface
3 Responses of the Oocyte
After Fusion with the Sperm
1. Cortical and Zonal Reactions
- prevents polyspermy through the release of
cortical oocyte granules containing lysozymes
a.) oocyte becomes impenetrable to other sperms
b.) zona pellucida alters its structure and
composition to prevent other sperm binding and
penetration
2. Resumption of the 2nd Meiotic Division
– resulting in 2 daughter cells
3. Metabolic Activation of the Egg
- activating factor probably carried by the sperm
Main Results of
Fertilization
1. Restoration of the diploid # of
chromosomes

2. Determination of the sex of the new


individual (x-carrying sperm  xx 
female ; y-carrying sperm  xy  male)

3. Initiation of cleavage
Clinical Correlates

Methods of Contraception:
1. barrier techniques – condoms,
diaphragm
2. oral contraceptives or pills
3. Depo-provera – subdermal implant or
intramuscular injection
4. IUDs
5. Vasectomy or tubal ligation
Clinical Correlates

Male Infertility – due to insufficient # of


sperm and/or their motility
- volume per ejaculation = 3-4 ml
- sperm/ml = 100M
- 20M sperm/ml or 50M sperm/total
ejaculation => normal
Clinical Correlates
Female Infertility
- due to occluded oviduct (ffg. PID)
hostile cervical mucus
immunity to sperm
no ovulation
IVF = in vitro fertilization
GIFT = gamete intrafallopian transfer
ZIFT = zygote intrafallopian transfer
Cleavage
zygote

2-cell stage

mitosis

Blastomeres
(increase in cell number)

8-cell stage

16-cell stage
(morula)
Cleavage
Morula
(In the uterine cavity
3 days after fertilization)

blastocyst

Inner cell mass Outer cell mass

embryoblast trophoblast

6th day

implantation
Implantation

occurs in the endometrium along the


posterior or anterior wall of the body
of the uterus
- embedded between the opening of
the gland
Implantation
Cleavage
Morula
(In the uterine cavity
3 days after fertilization)

blastocyst

Inner cell mass Outer cell mass

embryoblast trophoblast

6th day

implantation
Trophoblast

Differentiates into 2 layers:

1. Cytotrophoblast – inner,
mononucleated
2. Syncytiotrophoblast – outer,
multinucleated
Embryoblast

Differentiates into 2 layers (bilaminar germ


layer):
1. Hypoblast – adjacent to the blastocyst
cavity
2. Epiblast – adjacent to the amniotic cavity

Amnioblast – epiblasts adjacent to the


cytotrophoblast, lines the amniotic cavity
9th Day AOG

- Exocoelomic or
Heuser’s membrane

- Exocoelomic Cavity
= Primitive Yolk Sac
Uteroplacental Circulation
 sinusoid (maternal capillaries) eroded by the deep
penetration of the syncytiotrophoblast into the
endometrial stroma
 establishes maternal blood flow to the embryo
13th Day AOG
 bleeding may occur at the implantation site
due to increase blood flow into the lacunar
spaces
 occurs near the 28th day of the menstrual
cycle thus confused with menses
 connecting stalk – only place where the
extraembryonic mesoderm traverses the
chorionic cavity  becomes the umbilical
cord as it develops blood vessels
Clinical Correlates
hCG = human chorionic gonadotropin
- produced by the syncytiotrophoblast
- detected by end of the 2nd week of gestation via
RIA (pregnancy test)

Reasons why the conceptus is not rejected since 50%


is of paternal origin:
1. Resistance of the syncytiotrophoblast to killer
cells
2. Absence of transplantation antigens in the
syncytiotrophoblast surface
Clinical Correlates

Ectopic Pregnancy
- extrauterine pregnancy

- ovarian, abdominal cavity, rectouterine


area (Douglas’ pouch)
Clinical Correlates

Hydatidiform mole
- trophoblast develops placental membrane
but little or no embryonic tissue
- benign or malignant (invasive mole,
choriocarcinoma)
- arise from fertilization of an oocyte lacking
in nucleus followed by duplication of the
male chromosome to restore the diploid #
- suggests that paternal genes regulate most
of the development of the trophoblast
Gastrulation
 process of establishing the 3 germ layers
in the embryo
 starts with the formation of the primitive
streak on the surface of the epiblast
(source of all the germ layers of the
embryo – ectoderm, mesoderm and
endoderm)
 highly sensitive stage for teratogenic
insults
Primitive Streak
 visible by Day 15-
16 of development
 primitive node
 primitive pit
Notochord

 underlies the neural tube


 serves as the basis for the axial skeleton
Embryonic Disc

 expands mainly in the cephalic region


due to the continuous migration of
cells from the primitive streak region
 differentiation of germ layers
commence:
– mid 3rd wk AOG = cephalic part
– end 4th wk AOG = caudal part
 embryo develops cephalocaudally
Clinical Correlates

Ethanol
 kills cells in the antero-midline of the
germ disc
 deficiency of midline craniofacial
structures
 eg. holoprocencephaly
Clinical Correlates
Serenomelia
= Caudal Dysgenesis
 due to insufficient
mesoderm formed in
the caudalmost region
of the embryo
 contributes to lower
limbs, urogenital
system & lumbosacral
vertebrae
 risk factor- maternal
diabetes mellitus
Clinical Correlates
Sacrococcygeal Teratoma
 remnants of the
primitive streak
persists in the
sacrococcygeal area
 contains tissues
derived from the 3
germ layers
 most common tumor in
the newborn
Development of the Trophoblast

Primary villi

Secondary villi

Tertiary villi
= definitive placental villus
-differentiation of core into
blood cells & small vessels
forming the villous capillary sys
-establish contact with the
intraembryonic circulatory sys
 connecting placenta & the embryo
Development of the Trophoblast

Stem or anchoring villi


 from chorionic plate to the decidual
basalis

Free or terminal villi


 branch from sides of the stem villi

 responsible for exchange of nutrients


Development of the Trophoblast

Umbilical Cord
 establishes attachment between the
embryo and the placenta as a narrow
connecting stalk at its trophoblastic
shell on Day 19-20 of development
Embryonic Period

 3rd – 8th weeks of gestation


 period of organogenesis
 establishment of the main organ
systems
Induction
 involves stimulation of a responding tissue or group
of cells by an inducing tissue
 signalling molecules:
– transforming growth factor β (TGF-β) family
 activin
 fibroblast growth factor (FGF)
– Morphogens – molecules that are present in
concentration gradients to which cells respond in a
dose-dependent manner
– triggers cascade of events where the initial process is
activation of the homeobox genes
 retinoic acid
 neurotransmitters
 products of the Wnt genes
Neurulation
 process where the ectoderm overlying the
notochord thickens and forms the neural
plate, which is made of neuroectoderm cells
 neural folds, neural groove, neural tube
– D25 = complete closure of the cranial neuropore
– D27 = complete closure of the caudal neuropore
Neurulation
 once completed, the CNS is represented by:
– spinal cord = caudal portion
– brain vesicles = cephalic portion, characterized by a
# of dilatations
 neural crest gives rise to:
– spinal or sensory and autonomic ganglia
– parts of the ganglia of the CN V, VII, IX,& X
– Schwann cells, meninges (pia & arachnoid)
– melanocytes
– medulla of the suprarenal or adrenal glands
– bones & connective tissues of the craniofacial
structures & cells of the conotruncal cushion of the
heart
Neuralation

Bilateral ectodermal thickenings at the


cephalic region of the closed neural
tube forms the:
1. Otic placodes – forms the otic
vesicles (structures for hearing and
maintenance of balance)
2. Lens placodes – forms the lens of the
eyes
Ectoderm gives rise to the ffg:

 central nervous system (CNS)


 peripheral nervous system (PNS)
 sensory epithelium of the eye, ear & nose
 epidermis, including hair & nails
 subcutaneous glands
 mammary glands
 pituitary gland
 enamel of the teeth
Derivatives of the Mesoderm

Paraaxial Mesoderm
Lateral Plate – divided into 2 layers:
1. somatic or parietal mesoderm – lateral &
ventral body wall
2. splanchnic or visceral mesoderm – wall of
the gut
Intermediate Mesoderm – forms the excretory
units of the urinary system & the gonads
1. nephrotomes – cervical & upper thoracic
regions
2. nephrogenic cord – caudal regions
Somitomeres
 segments formed by the organization of the
paraaxial mesoderm
– head region = neuromeres
– occipital region caudally = somites
 42 – 44 pairs by the 5th week of development
 develops in a cephalocaudal sequence
 4 occipital + 7 cervical + 12 thoracic + 5 lumbar + 5
sacral + 8-10 coccygeal
 1st occipital + last 5-7 coccygeal somites disappear &
the remaining somites forms the axial skeleton
Somitomeres forms the:

1. dermis & subcutaneous tissue of the skin


2. sclerotome (bone & cartilage)
3. myotome(segmental muscle component)
4. dermatome (segmental skin component)

-cells forming the:


1. ventral and medial walls of the somite
vertebral column
2. dorsal somites  dermatomyotome =
provides musculature
Blood and Blood Vessels

Angioblasts – cells from


visceral mesoderm
that differentiates
into blood cells &
vessels
Angiogenic Cell Clusters

1. primitive blood cells
2. endothelial cells
lining the blood
islands; form small
vessels
Mesoderm gives rise to the:

 supporting tissues such as cartilage, bone,


connective tissues
 striated & smooth musculature
 blood & lymph cells & the walls of the
heart, blood & lymph vessels
 kidney, gonads and their corresponding
ducts
 cortical portion of the suprarenal gland
 spleen
Derivatives of the
Endoderm
Gastrointestinal tract
- main organ system derived from the
endodermal layer
- formation is greatly dependent on :
- cephalocaudal folding (CNS)
- lateral & transverse folding (somites)
- passive event – inversion & incorporation of
part of the endoderm-lined yolk sac into the
body cavities
Endoderm gives rise to the:

1. epithelial lining of the respiratory tract


2. parenchyma of the thyroid,
parathyroid, liver & pancreas
3. reticular stroma of the tonsils &
thymus
4. epithelial lining of the urinary bladder
& urethra
5. epithelial lining of the tympanic cavity
& auditory tube
Main external features
of the embryo at 2nd
month AOG
- somites &
pharyngeal arches
Thus, age of the
embryo can be
expressed in
somites
Crown-Rump Length
(CRL)
 measures from
vertex of the skull
to the midpoint
between the apices
of the buttocks
 approximates age
of the embryo (due
to variation in the
degree of flexure of
each embryo)
Crown-Rump Length
(CRL)
Clinical Correlates

Embryonic Period = period of


organogenesis
- 3rd – 8th weeks age of gestation (AOG)
- when most major organs are formed
- critical period for normal development
- 3rd – 4th week AOG – most vulnerable
- period when most gross structural birth
defects are induced
Fetal Period

 3rd month of gestation until birth


 characterized by:
– maturation of tissues and organs
– rapid growth of the body
 length of the fetus is measured by:
– Crown-rump-length (CRL)
– Crown-heel-length (CHL)
Fetal Period

 growth in length is particularly striking


during the 3rd-5th month of gestation
 increase in weight during the last 2
months of gestation

– Length = approx. 5 cm / month


– Weight = approx. 700 gm / month
Fetal Period
 relative slow down
in growth of the
head compared to
the rest of the body
– 3rd month = size of
the head approx. ½
CRL
– 5th month = 1/3 CRL
– Birth = ¼ CRL
Fetal Period (3rd month)
 face becomes more
human looking
 (+) primary ossification
centers (long bones &
skull)
 (+) reflex activity 
muscular activity
 (+) external genitalia
 formation of the GIT
Fetal Period
(4 -6 month)
th th

 fetus lengthens rapidly


 weight approx.< 500 gms
 (+) lanugo, head hair and eyebrows
 (+) quickening by 5th month = fetal movement
recognized by the mother
 skin is reddish & wrinkled due to lack of
underlying connective tissues
 CNS & respiratory system is not yet
differentiated sufficiently & coordination not yet
well established
Fetal Period
(7 - 8 month)
th th

 (+) vernix caseosa


= secretory product
from sebaceous
gland
 able to survive if
born prematurely
but may encounter
some difficulty
Fetal Period (9th month)

 skull has the largest circumference of


all parts of the body
 Normal values at birth (average):
– Weight = 3000-3400gms
– CRL = 36 cm
– CHL = 50 cm
– HC = 35 cm
Fetal Period

 whole length of normal pregnancy


– 280 days = 40 weeks after onset of LMP
– 266 days = 38 weeks after fertilization
 Expected date of confinement (EDC)
= 40 weeks + 2 weeks (38-42 weeks)
 Preterm or premature = < 36 weeks
 Postterm or postmature = > 42 weeks
Ultrasound

 utilizes the following parameters to


estimate fetal age
– CRL = during the 7th – 14th weeks
– Biparietal diameter (BPD) = 16th – 30th
week
– Head circumference (HC)
– Abdominal circumference (AC)
– Femoral length (FL)
Clinical Correlates

Intrauterine growth retardation (IUGR) –


infants born at or below 10th percentile
for their expected wt at a given age
Small for gestational age (SGA) – fetally
malnourished
Large for gestational age (LGA) – infants
of diabetic mothers
Intrauterine Insults
1. Chromosomal abnormalities
2. Teratogens
3. Congenital infection (TORCHs)
4. Maternal health (HTN, renal & cardiac
dses.)
5. Maternal nutritional status & socioeconomic
level
6. Maternal use of cigarettes, alcohol & other
drugs
7. Placental insufficiency
8. Multiple births
Assessment of Growth &
Development in Utero
1. Ultrasound
• least traumatic, no radiation
• determines placental & fetal size &
position
• determines multiple births &
malformations (neural tube defect,
congenital cardiac abnormalities &
abdominal wall defects)
Assessment of Growth &
Development in Utero
2. Amniocentesis = 20-30ml of amniotic fluid
• done after the 14th week AOG in order to
have sufficient AF
• used to analyze for αFP (increase in spina
bifida, anencephaly & abdominal wall
defects)
• 0.5% risk of fetal loss (abortion)
• fetal cells can be grown in cultures to detect
chromosomal abnormalities
Assessment of Growth &
Development in Utero
3. Chorionic villus sampling (CVS)
• 8th weeks AOG
• used to analyze for chromosomal
abnormalities & biochemical defects
(eg inborn error of metabolism)
• 0.8% risk of fetal loss
High Risk Pregnancies

1. advance maternal age (>35 yrs old)


2. history of neural tube defect in the family
3. birth of previous child with chromosomal
abnormalities
4. chromosome abnormalities between either
parents
5. mother is a carrier of a x-linked recessive
disorder (eg. thalassemia)
Tape of Ultrasound
Structure of the Placenta

2 components Formed by: Bordered by:


(4th mon AOG)
Fetal portion chorion chorionic plate
fondosum
Maternal decidua decidual plate
portion basalis
Placenta

- enlarges throughout pregnancy


- occupies approx. 15-30% of the internal surface of the
uterus
- increases in thickness due to arborization of existing
vessels
- mature placenta contains approx. 150ml of blood & is
replenished about 3-4x/min
- placental exchange does not take place in all villi, only
those in which fetal vessels are in intimate contact with
the covering syncytial membrane
- torn from the uterine wall approx. 30 mins. after birth of
the baby
Placental Membrane
 separates maternal & fetal blood
 not a true barrier since many substances
pass through it freely (hemochorial type)
 composed of 4 layers:
1. endothelial lining of the fetal vessels
2. connective tissue of the villus core
3. cytotrophoblastic layer
4. syncytium
Placental Circulation
cotyledon receives blood thru 80-100 spiral arteries that pierce the
decidual plate & enter the intervillous spaces

increase pressure in the lumen of the narrow spiral arteries

forces the blood deep into the intervillous spaces with oxygenated blood

pressure decreases & blood flows back from the chorionic plate
toward the decidua where it enters the endometrial veins
Functions of the Placenta

1. exchange of gases
2. exchange of nutrients & electrolytes
3. transmission of maternal antibodies
4. hormone production
5. protective barrier against damaging
factors
6. detoxification of some drugs
Functions of the Placenta

Gas Exchange
- simple diffusion = O2, CO2 and CO
- at term, fetus extracts 20-30 ml
O2/min from the maternal circulation
- the amount of O2 reaching the fetus is
primarily dependent on placental
blood flow and not diffusion
Functions of the Placenta

Exchange of Nutrients &


Electrolytes
- amino acids, free fatty acids,
carbohydrates and vitamins
- exchange increases as pregnancy
advances due to increase demand
Functions of the Placenta

Transmission of Maternal Antibodies


- maternal Ab taken up by the pinocytes by
the syncytiotrophoblast then transported to
fetal capillaries
- mainly IgG class
- provides passive immunity against
diphtheria, smallpox and measles (fetus has
little capacity to produce its own Ab until
after birth
Functions of the Placenta
(Clinical Correlates)
Erythroblastosis fetalis or Hemolytic Disease of
the Newborn
- Fetus = Rh (+) Mother = Rh (-)
- fetal RBC invading the maternal bloodstream may elicit
an Ab response in the mother  intrauterine death of 2nd
child
- diagnosed by analysis of the amniotic fluid
- prevented by: intrauterine blood transfusion or exchange
transfusion after birth; injection of Rh immunoglobulin
(Rhogam) to the mother

ABO Incompatibility – less fatal, jaundice


- Mother = Type O Fetus = Type A or B or AB
- observe ; exchange transfusion in severe cases
Functions of the Placenta
Hormone Production
- all hormones are synthesized in the syncytial trophoblast
- progesterone = to maintain pregnancy
- estrogen (predominantly estradiol) = stimulates uterine
growth & development of the mammary gland of the
mother
- human chorionic gonadotrophins (hCG) = excreted in
mother’s urine, used for PT
- placental lactogen (somatomammotropin) = growth
hormone-like subs that gives the fetus priortiy on maternal
blood glucose & makes mother somewhat diabetogenic
Functions of the Placenta
(Clinical Correlates)
Diethylstilbesterol (DES)
- synthetic estrogen
- easily crosses the placenta

- causes carcinoma of the vagina and abnormal


testes
Danazol
- androgen analog

- causes musculinization of the female fetus 


pseudohermaphrodite
Functions of the Placenta

Protective Barrier
- viruses which traverse the placenta
without difficulty = rubella (measles),
rubeola (German measles), variola
(smallpox), varicella (chickenpox),
coxsackie, CMV, poliomyelitis
Detoxification of Some Drugs
- fetal drug addiction = heroin
Umbilical Cord
 2 arteries and 1 vein
 Physiologic umbilical hernia – the abdominal
cavity is temporarily too small for the rapidly
developing intestinal loops and some are pushed
into the extraembryonic coelomic space in the
umbilical cord
 Jelly of Wharton – proteoglycan-rich subs.
which surrounds the umbilical cord & serves as a
protective layer to the blood vessels
 approx. 2 cm diameter & 50-60 cm long, tortous
– extremely long  cord coil  fetal asphyxia
– short  difficult attachment of the placenta
Amniotic Bands
 due to tears in the amion
 scar-like tissue
constricting part of the
fetus (limbs or digits)
 origin of the bands is
probably infections or
toxic insults that involve
either the fetus, fetal
membrane or both
 may result in :
amputations, ring
constrictions, craniofacial
deformities
Placental Changes at the End of
Pregnancy (indicates reduce
exchange)
1. increase fibrin tissue in the core of the
villus
2. increase thickness of the basement
membrane in the fetal capillaries
3. obliterative changes in small capillaries
of the villi
4. deposition of fibrinoid on the surface of
the villi in the junctional zone & in the
chorionic plate
Amniotic Fluid
 clear, watery fluid produced by amniotic
cells
 derived primarily from maternal blood
 amount increases as pregnancy
advances
– 30 ml = 10 wks AOG
– 350 ml = 20 wks AOG
– 800-1000 ml = 37 wks AOG
Amniotic Fluid
 volume is replaces every 3 hours
 by 5th month AOG – fetus swallows
approx. 400 ml/day
 fetal urine – mostly water – added daily to
the amniotic fluid (since placenta functions
as an exchange of metabolic wastes)
 during labor, amniochorionic membrane
forms a hydrostatic wedge that helps
dilate the cervical os
Functions of the Amniotic
Fluid
1. absorbs jolt
2. prevents adherence of the embryo to
the amnion
3. allows for fetal movement
Clinical Correlates
Premature Rupture of Membranes (PROM)
- may cause infection- both mother & baby

Oligohydramnios = < 400 ml


- due to renal agenesis

Polyhydramnios or Hydramnios
- 1500ml - 2000ml

- due to : idiopathic cause, maternal diabetes,


congenital malformation (CNS – anencephaly, GI
defects - atresias)
Fetal Membranes in Twins
(Dizygotic Twins)
= fraternal twins
- more common (2/3 of twin pregnancies)

- incidence increases with maternal age

- simultaneous shedding of 2 oocytes &


fertilization by 2 different sperms
- totally different genetic constitution

- separate implantation = own placenta, own


amnion, own chorionic sac
- erythrocyte mosaicism = different blood types
Dizygotic Twins
Fetal Membranes in Twins
(Monozygotic Twins)
= identical twins
- develops from a single fertilized ovum
- results from splitting of the zygote at various stages of
development
- earliest separation is during the 2-cell stage  develops
2 separate zygote
- mostly splits at the early blastocyst stage  common
placenta & chorionic cavity but separate amniotic cavity
- Rarely splits at the bilaminar germ disc stage
- strong resemblance in blood group, fingerprints, sex &
external appearance
Monozygotic Twins
Clinical Correlates

Twins
- higher incidence of perinatal morbidity
and mortality
- high tendency toward preterm labor
and low birth weight
Clinical Correlates

Vanishing Twin
- refers to death of 1
fetus
- occurs in the 1st
trimester or early 2nd
trimester
- due to resorption or
formation of fetus
papyraceus
Clinical Correlates
Twin Transfusion Syndrome
- occurs in 5-15% of
monochorionic, monozygotic
twins
- placental vascular
anastomoses are formed
such that 1 twin receives
most of the blood flow while
the other is compromised
- results in larger 1 twin
- poor outcome (death of both
twins in 60-100% of cases)
Clinical Correlates

Conjoined Twins
= Siamese Twins
- incomplete splitting of the axial area of the germ disc

- classified accdg. to nature & degree of union


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