Cardiovascular System Development
© Dr Mark Hill (2011)
Development of the heart and vascular system begins very early in mesoderm both within (embryonic) and outside (extra embryonic) the embryo.
Vascular development therefore occurs in many places, the most obvious though is the
early forming heart, which grows rapidly creating an externally obvious cardiac "bulge" on the early embryo.
Stage 11 embryo heart bulge
The heart forms initially in the embryonic disc as a simple paired tube inside the forming pericardial cavity, which when the disc folds, gets carried into the correct anatomical position in the chest cavity.
Embryonic Heart (More? Dr ML Kirby | Heart Movies)
Throughout the mesoderm, small regions differentiate into "blood islands" which contribute both blood vessels (walls) and fetal red blood cells.
These "islands" connect together to form the first vessels whcih connect with the heart tube.
Fetal blood and vessel
A key aspect of heart development is the septation of the heart into separate chambers. As the embryonic/fetal circulation is different to the neonatal circulation (lung/pulmonary activation), several defects of heart septation may only become apparent on this
transition. One septal "defect" occurs in us all, the foramen ovale (between the 2 atria) which in general closes in the neonate over time.
Stage 13 heart cross-section
The peripheral vasculature can be thought of as 3 aortic/venous circulatory systems: placental (unbilical), embryonic and vitelline.
The placental system develops mainly in the extraembryonic mesoderm of the chorion, receives maternal nutrition, removes embryonic
waste and is lost with the placenta at birth
The vitelline system covers the surface of the yolk sac and contributes to the portal system (between gut and liver).
The embryonic system begins symmetrically (L/R) within the embryo, and is extensively remodelled, in particular in the pharyngeal arches, to
mature into our cardiovascular system.
Embryonic Heart Rate (EHR), early in development the heart starts to spontaneously beat
and a recent study by Wisser and Dirschedl in dated human embryos
showed an increase up to 63 postmenstrual days or 22 mm greatest length. Thereafter a steady decrease of EHR was noted.
Maximal EHR is reached when morphological development of the embryonic heart is completed. (see EHR Page).
Page Links: Introduction | Reading | Computer Activities |
Objectives | Learning activities | Development Overview |
Cartoon Heart Development | Heart Layers | Heart Volume |
Blood flow through the Embryo | Pig Overview | References | Glossary | Terms |
Related Pages: Abnormalities | Stage 13/14 | Stage 22 | Stage 22 Selected Highpower | Heart Rate | Blood | Blood Vessels | Molecular | Lymphatic
Some Recent Findings
Molina FS, Faro C, Sotiriadis A, Dagklis T, Nicolaides KH.
Heart stroke volume and cardiac output by four-dimensional ultrasound in normal fetuses.
Ultrasound Obstet Gynecol. 2008 Aug;32(2):181-7.
"In normal fetuses the stroke volume and cardiac output increase between 12 and 34 weeks' gestation. The extent to which, in pathological pregnancies, possible deviations in these measurements from normal prove to be useful in the prediction of outcome remains to be determined."
Watanabe Y, Kokubo H, Miyagawa-Tomita S, Endo M, Igarashi K, Aisaki KI, Kanno J, Saga Y.
Activation of Notch1 signaling in cardiogenic mesoderm induces abnormal heart morphogenesis in mouse. Development. 2006 May;133(9):1625-34.
"...Our present study thus indicates that the Notch1 signaling pathway plays a suppressive role both in AV myocardial differentiation and the maturation of the ventricular myocardium." (More? Notch Notes)
- Human Embryology (2nd ed.) Larson Ch7 p151-188 Heart, Ch8 p189-228 Vasculature
- The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch14: p304-349
- Before we Are Born (5th ed.) Moore and Persaud Ch12; p241-254
- Essentials of Human Embryology Larson Ch7 p97-122 Heart, Ch8 p123-146 Vasculature
- Human Embryology Fitzgerald and Fitzgerald Ch13-17: p77-111
Search PubMed- Medline
(More? Additional References)
- Describe the main features of heart development to the four-chambered system.
- Describe the development of the pericardium.
- Describe the development of primary and secondary atrial septa and the ventricular septum.
- Explain the changes occurring in the bulbis cordis and truncus arteriosus in its transformation from a single to a double tube.
- Describe the development of the aortic arches on the right and left sides from the fetus to the adult.
- Describe the development of arteries and veins.
- Describe the developmental aberrations responsible for the following malformations: patent ductus arteriosus (P.D.A.); atrial septal defects (A.S.D.) and ventricular septal defects (V.S.D.); tetralogy of Fallot.
- Review the developmental principles of the C.V.S.
- Examine the models and diagrams of the developing heart and list the main stages in heart development.
- Examine images of the 6mm pig and 8 week human embryos identifying the main features of the C.V.S.
- Relate developmental principles of the heart to the gross anatomy models.
- Introductory session on the development of blood, blood vessels and lymphatics.
- Discuss the selected malformations P.D.A., A.S.D. and V.S.D. and tetralogy of Fallot giving special reference to the developmental
aberrations causing the malformations and the consequences of the malformations on the individuals.
- Below is a summary of development. Alternatively read these listed recent reviews.
- forms in mesenchyme of precordal plate region
- cardiogenic region
- growth and folding of the embryo moves heart ventrallly and downward into anatomical position
- week 3 begins as paired heart tubes
- fuse to form single heart tube
- begins to beat in Humans- day 22-23
- heart tube connects to blood vessels forming in
- splanchnic mesoderm
- extraembryonic mesoderm
- Week 2 pair of thin-walled tubes
- Week 3 tubes fused, truncus arteriosus outflow, heart contracting
- Week 4 heart tube continues to elongate, curving to form S shape
- Week 5 Septation starts, atrial and ventricular
- Septation continues, atrial septa remains open, foramen ovale
- Week 40 At birth pressure difference closes foramen ovale leaving a fossa ovalis
- blood vessel formation
- also occurs in adult and disease
- begins week 3 in extraembryonic mesoderm
- yolk sac
- connecting stalk
- Growth Factors
- Vascular endothelial growth factor (VEGF), PIGF
- Angiogenesis 2
- angioblasts form clusters - blood islands
- blood islands extend and fuse together
- forms a network
- 2 populations of cells
- peripheral- form endothelial
- core- form blood cells
- all vessels (arteries and veins) appear initially the same
- Blood formation
- blood formation occurs later (week 5)
- occurs throughout embryoic mesenchyme
- then spleen, bone marrow, lymph nodes
- Vascular systems
- one vascular system with 3 components
- each component has own system of artery
- Vitelline Blood vessels
- cover entire surface of yolk sac
- connect to embryo through yolk stalk
- arises from dorsal aorta
- contribute to adult GIT arteries
- empties into sinus venosus
- contribute to the adult portal
- Embryo Blood vessels (systemic)
- will form the most of the cardiovascular
- some vessels have neural crest
- aortic sac -> aortic arches ->
dorsal aorta - umbilical artery
- dorsal aorta
- paired initially and fuses
- gives off segmental arteries
- 3 pairs of veins empty into the sinus
venosus of the heart
- vitelline, umbilical (only left
persists), common cardinal veins
- cardinal veins- anterior, common,
- systemic circulation
- Placental Blood vessels
- form initially in the connecting stalk
(then umbilical cord)
- anastomose in chorioni
- extend maternally toward chorionic
- extend embryonically to the sinus venosus
and dorsal aorta
- Placental Vessels
- carry deoxygenated blood (from dorsal
aorta) and waste products to the placental
- paired initially then only left at end
of embryonic period
- carry oxygenated blood to the embryo
Blood flow through
Maternal Blood | -> umbilical vein ->
liver -> anastomosis -> sinus venosus ->
atria ventricles-> truncus arteriosus ->
aortic sac -> aortic arches-> dorsal
aorta-> pair of umbilical arteries | Maternal
This is shown on the stage
13/14 pig G6 section.
Cartoon Heart Development
Transverse section- Heart is 2 tubes that fuse in the
midline anterior to pharynx.
The pericardial cavity can be imagined
as the top of the "horseshoe" of the
intraembryonic coelom. (where the arms
become the pleural cavity and the ends
fuse anteriorly to form a single
This view shows the initial positioning
of the ventricles above the atria. The
ventricles are rotated into their correct
anatomical position by the growth of the
heart tube, bending into an "S" shape.
Cardiac inflow- at the bottom (sinus venosus)
Cardiac outflow- at the top (truncus arteriosus)
pericardium - covers the heart. Formed by 3 layers consisting of a fibrous pericardium and a double layered serous pericardium (parietal layer and visceral epicardium layer).
myocardium - muscular wall of the heart. Thickest layer formed by spirally arranged cardiac muscle cells.
endocardium - lines the heart. Epithelial tissue lining the inner surface of heart chambers and valves.
|Heart Volume (ml)
||Lung Volume (ml)
*Table data is "embryonic age" while original reference used "gestational age" (from LMP)
(Data: Peralta CF, Cavoretto P, Csapo B, Falcon O, Nicolaides KH. Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation.
Ultrasound Obstet Gynecol. 2006 Feb;27(2):128-33.)
|Left Stroke Volume (ml)
||Right Stroke Volume (ml)
||Cardiac Output L/R (ml/min)
||2.39 / 1.8
||43.46 / 46.72
||284.71 / 365.99
*Table data is "embryonic age" while original reference used "gestational age" (from LMP). The stroke volume (SV) can be calculated from ultrasound measurement of end diastole volume (EDV) minus end systole volume (ESV); (SV = EDV - ESV).
(Data: Molina FS, Faro C, Sotiriadis A, Dagklis T, Nicolaides KH. Heart stroke volume and cardiac output by four-dimensional ultrasound in normal fetuses.
Ultrasound Obstet Gynecol. 2008 Aug;32(2):181-7.
Selected Lists of References from PubMed
March 1999 search results are available for
School of Anatomy computers without internet
access. Computers with internet access can
search from either Page
2 or PubMed
Search Pubmed Now
Click on the listed keywords below (used to search the external database) the most current references
on Medline will be displayed.
Cardiovascular Development Terms
For more cardiovascular term definitions and links to related topics use the glossary.
- angioblasts stem cells in blood islands
generating endothelial cells
- angiogenesis the formation of blood vessels
also called vasculogenesis in the embryo
- anlage (Ger. ) primordium,
structure or cells which will form a future
- atrial septal defects (A.S.D.)
- blood islands earliest sites of blood vessel
and blood cell formation, seen mainly on yolk sac
- branched villi or terminal villi, grow from
sides of stem villi, region of main exchange, surrounded
by maternal blood in intervillous spaces
- cardinal veins paired main systemic veins of
early embryo, anterior, common, posterior.
- cardiogenic region region above precordal
plate in mesoderm where ceart tube initially forms.
- cord knotting-
umbilical cord knotting occurs in 1%, prevents the
passage of placental blood. pseudoknots also occur
usually with no effect.
- cotyledons on maternal face of placenta, form
cobblestone appearance, originally placental septa formed
- cytotrophoblast extraembryonic cells of
trophoblastic shell surrounding embryo, contribute to
villi and placental membranes.
- decidua basalis-
- decidual reaction
- ectoderm the layer (of
the 3 germ cell layers) which form the nervous system
from the neural tube and neural crest and also generates
the epithelia covering the embryo.
- endoderm - the layer (of
the 3 germ cell layers) which form the epithelial lining
of the gastrointestinal tract (GIT) and accessory organs
of GIT in the embryo.
- endocardium - lines the heart. Epithelial tissue lining the inner surface of heart chambers and valves.
- endothelial cells single layer of cells
closest to lumen that line blood vessels
- extraembryonic mesoderm mesoderm lying
outside the trilaminar embryonic disc
- fetal erythroblastosis see Haemolytic
Disease of the Newborn
- haemocytoblasts stem cells for embryonic
blood cell formation
Disease of the Newborn fetal erythroblastosis, fetus
Rh+ /maternal Rh-, fetus causes anti Rh antibodies,
dangerous for 2nd child
- chorionic villi the finger-like extensions
which are the functional region of the placental barrier
and maternal/fetal exchange. Develop from week 2 onward
as: primary, secondary, tertiary villi.
- estrogens support maternal endometrium
- fetal drug addiction occurs when drugs used
maternally cross the placental barrier and can establish
addiction in the unborn fetus.
- growth factor
usually a protein or peptide that will bind a cell
membrane receptor and then activates an intracellular
signaling pathway. The function of the pathway will be to
alter the cell directly or indirectly by changing gene
expression. (eg VEGF, shh)
- hCG see Human chorionic
- Human chorionic gonadotrophin
(hCG) like leutenizing hormone, supports corpus
- Human chorionic
somatommotropin (hCS) or placental lactogen
stimulate mammary development
- Human chorionic thyrotropin (hCT) placental
derived hormone equivilant to thyroid
- Human chorionic corticotropin (hCACTH)
placental derived hormone equivilant to
- maternal antibodies immune molecules capable
of crossing placental barrier
- maternal decidua region of uterine
endometrium where blastocyst implants. undergoes
modification following implantation, decidual
- maternal sinusoids placental spaces around
chorionic villi that are filled with maternal blood.
Closest maternal/fetal exchange site.
- mesoderm the middle
layer of the 3 germ cell layers of the embryo. Mesoderm
outside the embryo and covering the amnion, yolk and
chorion sacs is extraembryonic mesoderm.
- myocardium - muscular wall of the heart. Thickest layer formed by spirally arranged cardiac muscle cells.
- neural crest cell
region at edge of neural plate, then atop the neural
folds, that remains outside and initially dorsal to the
neural tube when it forms. These paired dorsal lateral
streaks of cells migrate throughout the embryo and can
differentiate into many different cell
types(=pluripotential). Neural crest cells also
contribute to major cardiac outflow vessels.
- patent ductus arteriosus (P.D.A.)
- pericardium - covers the heart. Formed by 3 layers consisting of a fibrous pericardium and a double layered serous pericardium (parietal layer and visceral epicardium layer).
- pharyngeal arches (=branchial arches, Gk.
gill) form structures of the head. Six arches form but
only 4 form any structures. Each arch has a pouch,
membrane and groove.
- placenta (Gk. plakuos= flat cake) refers to
the discoid shape of the placenta, embryonic (villous
chorion)/maternal organ (decidua basalis)
- placenta accreta abnormal adherence of
placenta, with absence of decidua basalis
- placental arteries paired, carry deoxygenated
blood (from dorsal aorta) and waste products to the
- placental lactogen see Human
- placenta percreta villi of placenta penetrate
- placenta previa placenta overlies internal os
of uterus, abnormal bleeding, cesarian delivery
- placental veins paired initially then only
left at end of embryonic period, carry oxygenated blood
to the embryo (sinus venosus)
- primary villi week 2, first stage of
chorionic villi development, trophoblastic shell cells
(syncitiotrophoblasts and cytotrophoblasts) form
finger-like extensions into maternal decidua.
- protein hormone usually a protein distributed
in the blood that binds to membrane receptors on target
cells in different tissues. Do not easliy cross placental
- relaxin hormone
- secondary villi week 3, second stage of
chorionic villi development, extraembryonic mesoderm
grows into villi, covers entire surface of chorionic
- sinus venosus cavity into which all major
embryonic paired veins supply (vitelline, placental,
- splanchnic mesoderm portion of lateral plate
mesoderm closest to the endoderm when coelom forms.
- stem villi or anchoring villi,
cytotrophoblast cells attached to maternal tissue.
- steroid hormone lipid soluble hormone that
easily crosses membranes to bind receptors in cytoplasm
or nucleus of target cells. Hormone+Receptor then binds
DNA activating or suppressing gene transcription. Easliy
cross placental barrier.
- syncitiotrophoblast extraembryonic cells of
trophoblastic shell surrounding embryo, outside the
cytotrophoblast layer, involved with implantation of the
blastocyst by eroding extracellular matrix surrounding
maternal endometrial cells at site of implantation, also
contribute to villi. (dark staining, multinucleated)
- tetralogy of Fallot- Named after Etienne-Louis
Arthur Fallot (1888) who described it as "la maladie
blue". The syndrome consists of a number of a number
of cardiac defects possibly stemming from abnormal neural
- tertiary villi third stage of chorionic villi
development, mesenchyme differentiates into blood vessels
and cells, forms arteriocapillary network, fuse with
placental vessels, developing in connecting stalk
- umbilical cord
- umbilical cord knotting see cord
- vascular endothelial growth factor (VEGF)
protein growth factor family that stimulates blood vessel
growth, a similar factor can be found in the placenta
- ventricular septal defects (V.S.D.)
- virus small infectious agent able to cross
placental barrier. Can infect embryo and cause
developmental abnormalities. (e.g. cytomegalovirus,
- vitelline blood vessels blood vessels
associated with the yolk sac.
- waste products products of cellular
metabolism and cellular debris, e.g.- urea, uric acid,
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