Three phases of intrauterine life  Restoration of diploid number of chromosomes

o 23 pairs of chromosome (22 autosomes, 1 pair sex )

 Pre-embryonic phase
 Determination of chromosomal sex ( XX, XY)
 Embryonic period
 Initiation of cleavage
 Fetal period
o Cleavage of cell ( 2cell to 16 cell stage morula) occurs
Three processes 3-4 days after fertilization (3-4 days Stage 2)

 Implantation Morula
 Embryogenesis
 leaves 3-4 days after fertilization ( Stage 2)
 Placental development
Blastocyst
Age of gestation
 Inner cell mass – (embryoblast) embryo
 Menstrual age (Last menstrual period
 Outer cell mass – (trophoblast) – placenta
 Ovulatory age (based on ovulation/ fertilization)
 Blastocyst implants about 6-7 days after fertilization
 Example:
(implantation, Stage 3)
o 7 weeks ovulatory age
o 9 weeks AOG (menstrual age) Pre-embryonic (2 weeks after fertilization)
 Pre-embryonic – (2 weeks AOG) Embryonic –(3-8
 Blastocyst- partially embedded in the uterine mucosa
weeks AOG)fetal period (9 weeks to birth)
( 8days after fertilization)
Pre-embryonic Period  Differentiates to 2 types of cells: Cytotrophoblast and
syncitiotrophoblast
 Ovum  Positive pregnancy test (HCG)
 Zygote  Implantation
 Blastocyst o 3 phases
Ovary  Apposition
 Adhesion
 Cyclic release of gametes  Invasion
o Intrauterine – 5-7 million primordial germ cells  Ultrasound: thickened endometrium
o At birth – 2 million germ cells  Pregnancy test is positive (50 IU/L)
o Puberty – 400,000 oocytes  28th day cyc;e, bleeding occurs at the site of implantation
o >35 y/o -- <34,000  Hartman’s Sign  uteroplacental circulation
 Of the 200-300 million spermatozoa, only 300-500 reach  Bilminar embryo
the site of fertilization (fallopian tube)  Stage 5
 Ectoderm bordering amniotic cavity and endoderm
Fertilization bordering primitive yolk cavity
 Union of spermatozoa with an oocyte (viable within 24 Embryonic Period (3-8 weeks AOG)
hours)
 12-24 hours after ovulation 3 weeks AOG (after fertilization)
 Zygote (0-2 days Stage I)
 Process of gastrulation
Sperm  3 germ layers
o Ectoderm – nervous system, skin, hair, teeth, sweat
 Capacitation glands
 Acrosomal reaction o Endoderm- GIT, respiratory, urinary bladder, Liver,
Results of fertilization pancreas
o Mesoderm- muscle, vascular system, cartilage, Bones
 Trilaminar germ disc  Eyelids begin to develop
 Stage 6&7  Genital tubercle
 Primitive streak
8 weeks
 Stage 6, 7, 8
o Trilaminar germ disc  Stage 21-23
o Primitive streak  CRL = 30mm
o Neural plate  Prominent eyes (eyelids), auricle
 Stage 9  Well formed toes and fingers
o Thyroid gland  Elbow- upper limbs
o Connective tissue  Genital/urethral tubercle/anus
 Sexual differentiation
4th week
 Ends embryonic period
 Stage 10
9-10 weeks AOG
o Fetal heart
 Stage 11  Fetal period
o Pharyngeal arches  CRL = 45-50 mm
 Stage 12  Face (profile)
o Limb bud  Placenta functional
o Otic pit  Umbilical herniation  9 weeks AOG
 Stage 13
o CRL = 4 mm 12 weeks AOG

5 weeks gestational age  Gender first distinguished

 Active motion
 CRL = 5 mm  Primary ossification centers present in long bones and
 Presence of heart activity fetal skull
 Stage 14  Resolution of “Midgut herniation”
o Eye o Persistence leads to abdominal wall defects as
o Upper limb/lower buds omphalocele
 Stage 15
16 weeks AOG
o Hand plate
o Umbilical cord ( CRL = 8mm)  CRL: 12 cm
 Weight: 110 gms
6 weeks
 Fetal gender can be identified
 Stage 16, 17
Early ultrasound
o CRL = 10-13 mm
o Ear/eye mouth  Gestational age (crown rump length)
o Upper lip/ nise  Number of embryo (detected)
o Digits  Detect abnormal pregnancy
o Foot plate  Viability (+) cardiac activity at 6 weeks AOG
o (+) heartbeat by UTZ
2nd and 3rd trimester (gestational Age)
7 weeks
 Biparietal diameter
 Stage 18-19  Femur length
 Head bigger than the body  Abdominal circumference (weight)
 CRL = 16-18 mm
20 weeks AOG  7-8 days after fertilization,
o trophoblast proliferation and invasion
 Weight: 300 gms
o cytotrophoblast differentiates to syncitium
 Fetus is active ( quickening)
 9-11 days
 Fetal skin (transparent)
o Lacunar period
 Lanugo covers the body
o Maternal blood within the lacunae
24 weeks AOG  13-18 days
o Primary and secondary villi form
 Weight: 630 gms  18-21 days
 Eyebrows/hair visible o Tertiary villi (feto-placental unit formed)
 Fat deposition begins  21-40 days
 Canalicular lung development o Chorionic frondosum formed (fetal portion of
 Best time: (congenital scan 22-24 weeks) placenta)
o Deciduas basalis (maternal portion)
28 weeks AOG
 40-50 days
 Length: 25 cm o Cotyledons are formed
 Weight: 1,100 g
Development of Chorion and Decidua
 Skin: thin, red, covered with vernix caseosa (90%
survival)  Chorionic villi- in contact with deciduas basalis (leafy
 Thickened nuchal fold chorion) (chorion frondosum)
o >6mm “Down syndrome”  Villi in contact with deciduas capsularis becomes
avascular (chorion laeve)
32 weeks
Placenta hormones
 CRL: 28 cm
 Weight:1,800 gms  Protein hormones (HCG/HPL/ACTH/Thyrotropin)
 Skin: red and wrinkled  Hypothalamic like releasing hormone of the placenta
 Fetal surveillance test o GnRH,
o TRH,
36 weeks
o CRH,
 CRL: 32cm o GHRH
 Weight: 2,500g  Inhibin, activin
 >subcutaneous fat  Estrogen
 Progesterone
40 weeks
Human Chorionic gonadotropin
 Fully developed
 CRL: 36 cm  Pregnancy hormone
 Weight 3,400g  Half plasma life: 36 hours
 Glycoprotein (alpha and beta subunits)
Fetus is said to be
 Alpha-encoded on chromosome 6 (HCG, LH, FSH, TSH)
 Term when it is (280 days or 40 weeks AOG) or (266  Site of synthesis: before 5 weeks (cytotrophoblast/
days or 38 weeks) syncitiotrophoblast)
 Preterm when it is less than 37 weeks or 259 days  Maximal secretion: 8-10 weeks
 Post term after 42 weeks or more than 295 days  Peak maternal plasma volume: 60-80 days after menses
 Detectable by 7-8 days after LH surge by the time of
implantation
 Doubles every 2 days
Placenta
 GS (TVS) = 800-1,000 mIU/L  3 shunts (ductus venosus, formane ovale, ductus
 HCG levels arteriosus) allow oxygenated blood to bypass the RV and
o High during gestational trophoblast disease pulmonary circulation therefore flow directly to the LV
o Low during down’s syndrome and aorta
 Shunts and fetal ventricles work in parallel rather than
Human Placental lactogen (hPL) sequence as in adult
 Fetal CO is 3x higher than adult at rest
 Chorionic somatomammotropin
 Lipolytic, anti-insulin and prolactin like activities Three shunts
 Very little in fetal serum and urine
 Detected in maternal serum as early as 3 weeks and rises a. Ductus venosus
until 36 weeks  Fetal blood vessel connecting the umbilical vein to
the IVC
Placental estrogen  Blood flow regulated via sphincter
 Carries mostly hi oxygenated blood
 Most important source is the fetal adrenal gland
b. Foramen ovale
(precursor) DHEA-S
 Shunts highly oxygenated blood from right atrium to
 Several enzymatic reactions occur
left atrium
Fetal adrenal steroid precursor c. Ductus arteriosus
 Protects lungs against circulatory overload
 Cholesterol  Allows the right ventricle to strengthen hi pulmonary
 Fetal adrenal glands are highly dependant on LDL vascular resistance, low pulmonary blood flow
 Fetal conditions can affect estrogen production (fetal  Carries mostly med oxygen saturated blood
demise, anencephaly, adrenal hypoplasia etc)
Changes after birth
Fetal Physiologic development
 Increasing uptake of oxygen by lungs (first and
 Oxygenated blood (from mother) via umbilical vein subsequent breaths) induces a vasoconstriction of ductus
 Deoxygenated blood (from fetus) via umbilical artery venosus and ductus arteriosus
 Occlusion of placental circulation causes lowering of
blood pressure (IVC and RA) with increase in LA 
closure of Roramen ovale
Development of the Conceptus – Fetal
Aeration of Lungs at birth
Circulation
 Marked decrease in pulm. vascular resistance due to
lung expansion
Fetal Circulation  Marked increase in pulm. blood flow  increase LA
 CVS starts to develop at 4 weeks pressure above that of IVC
 Fetal heart starts to beat at 5 weeks  Progressive thinning walls of pulm vessels
 Critical time of development: 20-50 days after First breath
fertilization
 Alveoli open up (blood from RA rush to pulm vessels)
Fetal Physiologic development  P in the R side of heart decreases
 Oxygenated blood from the mother via umbilical vein  P in the L side of heart Increases (fr pulm veins)
 Deoxygentated blood from fetus via umbilical artery  P is high in the aorta  SYSTEMATIC CIRCULATION

Fetal circulation Changes after birth

 Fetal lung expands ( cord clamping)  Inhibition of swallowing – esophageal atresia
 DA- constriction (DA,FO,DV) adult type of functionally (polyhydramnios)
closed by 10-96 hrs, anatomically closed by 2-3 weeks  Meconium – dark greenish substance (biliverdin)
 FO functionally closed within few minutes 9 fusion of secretions and dequamations from GIT (passage maybe
septae 1 year after birth) due to hypoxia)
 DV – becomes ligamentum venosum
Amniotic Fluid
 DA – becomes ligamentum arteriosum
 Umbilical arteries – umbilical ligaments  Functions
 Umbilical vein – ligamentum teres o Medium where fetus can move
o Cushions fetus against injury
Patent ductus arteriosus
o Maintains temperature
 Depends on the oxygen tension between pulmonary o Test of fetal maturity (amniocentesis)
artery and aorta o Enhance visualization (UTZ)
 Oxygentension is mediated by PG action in the ductus o Acts as a wedge in dilating cervix (labor)
 PG synthetase inhibitors result to premature closure of o Suggests intrauterine problem (oligo/polyH)
the DA  Formation of AF
 Postnatal: PG inhibitors to effect closure of patent ductus o Amniotic membrane 912 weeks) of 50 ml
arteriosus o Midpregnancy (400ml) fetal urination
o Peaks to 1,000ml by 36-38 weeks
Fetal blood
o AF (Oligohydramnios<300ml, polyhydramnios>2L)
 Hematopoiesis (YS-embryo/ Liver –fetal) o Quantification (UTZ): subjective, single vertical
 Blood volume and Hgb concentration increases pocket (2-8cm), AFI (5-20cm)
progressively
Respiratory System
 Fetal hgb
o Hemoglobin F (2 alpha/2 gamma)  Stages of Lung development
o Hemoglobin A (adult) 2 alpha/2beta a. Pseudoglandular (5-16w) – gland
o Hemoglobin A2 (2 alpha/2 delta b. Canalicular (16-25w)-bronchioles
c. Terminal sac (>25w)- primitive alveoli/ surfactant
Fetal coagulation factors
(type II pneumocytes)
 Low levels – II, VI, X, XI, XII, XIII and fibrinogen  Surfactant
 Vit K dependant o Complex lipoprotein, 90% lipids specifically
 Risk of hemorrhagic disease of the newborn glycerophospholipids and 10% apoproteins
o Maintains surface tension of alveoli
Urinary system o RDS (insufficient)

 Embryonic (pronephros and mesonephros)  Endocrine System

metanephros
 Kidneys/ ureter (mesoderm)  Ant. Pituitary
 Bladder/ urethra (urogenital sinus) o Secretes hormones by end of 17 weeks (prolactin,
 Fetal kidneys _ (starts to produce urine by 12 weeks) GH, ACTH, TSH, FSH and LH)
 Urine production (10ml/h at 30 weeks, 27 ml/hr at term) o Post. Pituitary – oxytocin, ADH 10-12w
(650 ml/day) o Thyroid glands synthesize hormones (1—12w)
o Adrenals – larger in relation to total body size
Digestive system compared to adult adrenals, involutes rapidly after
 10-12 weeks – swallow (intestinal peristalsis) birth; synthesize aldosterone
o Gonads – synthesizes testosterone and estrogen
 Term – fetus swallows 9200-760 cc/day)
Placenta and Fetal membranes; fetal-maternal Fetoplacental circulation
communication
 Deoxygenated fetal blood (umbilical arterie to
Placental arm Paracrine arm placenta)
 Villous and extra villous  Fetal membranes  At the junction of umbilical cord and placenta, the
trophoblast (amnion and chorion umbilical arteries branch radially toform chorionic
laeve)
arteries
 In the villi, (extensive arteriocapillary venuous
Placenta and fetal membranes system)
 Brings fetal blood extremely close to the maternal
 Implantation of Blastocyst – inner most part of the blood but no intermingling of fetal and maternal
trophoblast invades the endometrium coalesce to blood occurs
become the syncitium
 Syncitiotrophoblast- derived from inner cytotrohoblast Amnion
 Cytotrophoblast – innermost layer (embryonic side)
 Develops 7-8 days of Blastocyst stage
nearest intravillous space
 Single layer nonciliated cuboidal epithelial cells
 Maternal blood directly bathes the villous trophoblasts
 5 layers (epith/BM/compact/fibroblast/spongy)
 Fetal blood contained within fetal capillaries and
 No smooth muscle, nerves, lymphatics, blood vessels
traverse the villi in the intervillous space
 0.2-0.5 mm thickness
 Fetal membrane (Chorion laevae)
 Active in water and solute transport
o With the growth of fetus (lost of blood supply with
the villous nature of chorionic frondosum  Umbilical cord
becomes avascular fetal membrane (chorion laevae)
 Chorion laevae – area not covered by villi  Covered by amnion
 Chorion frondosum fetal component of the placenta  Diameter 0.8-2 cm
 Deciduas basalis – maternal component of the placenta  Average length (55cm)
 Contains Wharton jelly
Placenta at term  Coils (helical twist of blood vessels, with predominance
of left sided twist)
 1/6th of fetal weight
 Umbilical coiling index (number of vascular coils/ length
 500 gms
of the cord)
 20 cm in diameter
 2-3cm thick
 10-38 cotyledons
 Fetal surface is covered by transparent amnion, chorionic
vessels
 Maternal surface – divided into lobes by septa

Placental circulation

 Maternal blood enters the intervillous space through

endometrial arteries (spiral arteries), 80-100 in number
 At the point where the artery enters, the blood is under
high pressure
 This pressure forces the blood deep into intervillous
spaces and bathes the villi