The three main arteries that develop in early human embryos are: 1) The dorsal aortae, which are the first major blood vessels to form and connect the heart to the developing vascular system. 2) The aortic arch arteries, which develop from the aortic sac to supply the pharyngeal arches as the embryo grows. 3) The umbilical arteries, which develop from the dorsal aortae and connect to the placenta to allow nutrient exchange with the mother. As the embryo develops, these major arteries and the accompanying vascular networks are refined through vasculogenesis and angiogenesis guided by growth factors to establish the adult circulatory system.

1. Development of Arteries
Image Source: Scanning electron micrographs of the Carnegie stages of the early human embryos are reproduced with the permission of Prof Kathy Sulik, from embryos
collected by Dr. Vekemans and Tania Attié-Bitach. Hill, M.A. 2017 Embryology Heart Tube Fusion.jpg

2. Overview
 Outline of time course
 Vasculogenesis and Angiogenesis
 Growth factors involved
 Brief mention of early vascular systems- Vitelline, Systemic
and Placental.
 Aortic Arch and Pharyngeal arteries
 Umbilical Arteries
 Segmental Arteries
 Vitelline Arteries
 Anomalies of arterial tree.

3. Introduction
 Development of the heart and vascular system begins very early in
mesoderm both within (embryonic) and outside (extra embryonic,
yolk sac and placental) the embryo.
•forms initially in splanchnic mesoderm of prechordal plate
region - cardiogenic region
• growth and folding of the embryo moves heart
ventrally and downward into anatomical position
•heart tube connects to blood vessels forming in splanchnic
and extraembryonic mesoderm
•Week 2-3 pair of thin-walled tubes
•Week 3 paired heart tubes fuse, 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 until
after birth, foramen ovale.
•Week 37-38 at birth, pressure difference closes foramen
ovale leaving a fossa ovals
Time course

4. Angioblastic mesenchyme
 Extraembryonic
mesenchyme in the
 splanchnopleure of the
yolk sac
 in the body
stalk(containing the
allantois)
 the somatopleure of the
chorion
 The peripheral cells flatten
as a vascular endothelium,
whereas the central cells
transform into primitive
red blood corpuscles.
 Later, contiguous islands
merge, forming a
continuous network of fine
vessels.
 Figure 6.15 Extraembryonic blood vessel formation in the villi,
chorion, connecting stalk, and wall of the yolk sac in a
presomite embryo of approximately 19 days. Langman’s
Embryology, 12th ed.

5. Growth factors involved
 Vascular Endothelial Growth Factor (VEGF) and Placental
Growth Factor (PGF) and Platelet derived Growth Factor
(PGDF)
 Growing blood vessels follow a gradient generated by target
tissues/regions of Vascular Endothelial Growth Factor (VEGF) to
establish a vascular bed.
 Notch signaling acts as an inhibitor for this system, preventing
sprouting of blood vessels. Notch is a transmembrane receptor
protein involved in regulating cell differentiation in many
developing systems.

6.  Figure 6.14 Blood vessels form in two
ways: vasculogenesis (top), in
which vessels arise from blood
and angiogenesis (bottom), in which
new vessels sprout from existing
During vasculogenesis, fibroblast
growth factor 2 (FGF-2) binds to its
receptor on subpopulations of
mesoderm cells and induces them to
form hemangioblasts. Then, under
influence of vascular endothelial
growth factor (VEGF) acting through
two different receptors, these cells
become endothelial and coalesce to
form vessels.
 Angiogenesis is also regulated
by VEGF, which stimulates
proliferation of endothelial cells at
points where new vessels will sprout
from existing ones. Final modeling
stabilization of the vasculature are
accomplished by platelet-derived
growth factor (PDGF) and
transforming growth factor β (TGF-β).
Langman’s Embryology, 12th ed

7.  Specification into arteries, veins and lymphatic begins soon
after the angioblast induction.
 For arterial development
 SHH VEGF Notch pathway ephrinB2
 EPHB4- vein specific gene
 Prox-1- lymphatics

8.  Till second week:
Diffusion through
the extraembryonic
coelom and
umbilical vesicle.
 Beginning of 3rd
week: Blood vessel
formation begins in
the extraembryonic
mesoderm of the
umbilical vesicle,
connecting stalk,
and chorion.
EARLY DEVELOPMENT OF
CARDIOVASCULAR SYSTEM: Vasculogenesis
Makoto Kamei, W Brian Saunders, Kayla J Bayless, Louis Dye, George E Davis, Brant M Weinstein Endothelial tubes
assemble from intracellular vacuoles in vivo.Nature: 2006, 442(7101);453-6 PubMed 16799567
Hill, M.A. 2017 Embryology Embryonic
Circulations.jpg. Retrieved November 24,
2017,
from https://embryology.med.unsw.edu.a
u/embryology/index.php/File:Embryonic_
Circulations.jpg

9. Blood formation: End of the 3rd
Week and thereafter
 Blood cells develop from specialized endothelial cells (hemangiogenic
epithelium) of vessels as they grow on the umbilical vesicle (yolk sac) and allantois
at the end of the third week
 Later (week 5) throughout embryonic mesenchyme
 The definitive hematopoietic stem cells are derived from mesoderm surrounding
the aorta in a site near the developing mesonephric kidney called the aortagonad-
mesonephros region (AGM).
 These cells colonize the liver, which becomes the major hematopoietic organ of the
embryo for a period of 2nd to 7th month of development.
Figure 1. The first definitive multipotent hematopoietic stem
cells (HSCs) are generated within the embryonic aorta-gonad-
mesonephros (AGM) region. The AGM extends from the
umbilicus to the anterior limb bud of the human embryo and
contains the dorsal aorta. Within the dorsal aorta, a cluster of
CD34+ hematopoietic cells is associated with the ventral floor
of the aorta.
Printed in the R&D Systems 2003 Catalog

10. Angiogenesis
 None of the main vessels of the adult arises as a single trunk in the embryo.
 A capillary network is first laid down along the course of each vessel
 The larger arteries and veins are defined by selection and enlargement of definite paths in this network.)
 Angioblasts, arising in splanchnic and somitic tissues, add endothelial sprouts and branches to earlier vessels.
Fig: 51- Dorsal view of
chick embryo with ten
pairs of mesodermal
somites: Bailey FR. and
Miller AM. Text-Book of
Embryology (1921) New
York: William Wood and
Co.

11. Capillary
Hemangioma
 Abnormally dense collection of
capillary blood vessels.
 Often associated with craniofacial
structures.

12.  Dorsal aortae are the first intra-embryonic
blood vessels to arise in the trunk.
 Primary dorsal aortae comprise a pair of
longitudinal vessels in which the anterior ends
are connected to the nascent heart via
outflow tracts and the posterior parts are
linked to vitelline arteries at the umbilicus
level.
 The anterior ends of the dorsal aortae are
connected with outflow tracts of heart, and
the posterior ends gradually elongate toward
the tail by connecting with the vascular plexus
in the splanchnic mesoderm.
Embryonic Arteries:
Dorsal Aortae
Fig. 13.1 The early,
symmetrical blood vascular
system. A, Ventrolateral view
of the endothelial profile of
the heart, the first aortic arch
arteries and the
dorsal aorta shown in
relation to the major
epithelial populations
Gray’s Anatomy. 41st ed

13.  After head folding, the embryo has
bilateral primitive aortae, each
consisting of ventral and dorsal
parts that are continuous through
the first embryonic aortic arch.
 The ventral aortae are fused and
form a dilated aortic sac.
 After head folding, the embryo has
bilateral primitive aortae, each
consisting of ventral and dorsal
parts that are continuous through
the first embryonic aortic arches.
 The dorsal aortae run caudally, one
on each side of the notochord. In
the fourth week they fuse from
about the level of the fourth
thoracic to that of the fourth lumbar
segment to form a single definitive
descending aorta.
Langman’s Embryology, 12th ed

14.  Mature endothelial channels are seen in
the rostral regions (aortic arches)
 Caudally, a changing capillary plexus
constantly remodels until it becomes
confluent with the vascular channels of
the connecting stalk.
 The dorsal continuation of the primitive
dorsal aortae directs blood into an
anastomosing network around the
allantois which will form the umbilical
arteries.
 Blood is channelled back to the
developing heart from the allantois via
Umbilical veins, from anastomoses in
the primitive yolk sac via the Vitelline
veins, and from the body via pre- and
post-cardinal veins that join to form the
common cardinal veins
The developing human: Clinically oriented embryology
(10th edition) By Keith L. Moore and T.V.N. Persaud.
Philadelphia: W. B. Saunders, 2015.

15. EMBRYONIC ARTERIES
 Aortic Arch Arteries
 Somatic arteries (Intersegmental)
 Umbilical arteries
 Lateral splanchnic arteries
 Ventral splanchnic arteries (Vitelline)

16. Aortic Arches
 The aortic arches initially develop by
vasculogenesis, soon after neural crest cells
have invaded the early pharyngeal arches.
 Angiogenic mesenchyme forms the
endothelial lining of the vessels and neural
crest contributes to the outer layers of the
walls.
 The first aortic arch artery is part of the
original vascular circuit that links the truncus
arteriosus of the heart to the paired dorsal
aortae.
 As the heart descends relative to the
forebrain and other rostral structures, the
aortic sac (the most distal part of
the truncus arteriosus) gives rise to
paired aortic arches at successively more
caudal levels, each of which passes laterally
on each side of the pharynx to join the
dorsal aortae.
Langman’s Embryology, 12th ed

17. Aortic Sac
 The pharyngeal arches and their
vessels appear in a cranial-to-
caudal sequence.
 Five arches are numbered I, II, III,
IV, and VI
 Division of the truncus arteriosus
by the aorticopulmonary septum
divides the outflow channel of the
heart into the ventral aorta and
the pulmonary trunk.
 The aortic sac then forms right
and left horns, which
subsequently give rise to the
brachiocephalic artery and the
proximal segment of the aortic
arch, respectively.
Langman’s Embryology, 12th ed

18. Arch Arteries
1st and 2nd
 By day 27, most
of the first aortic
arch has
disappeared,
although a small
portion persists
to form the
maxillary artery.
 Second aortic
arch soon
disappears. The
remaining
portions of this
arch are- the
hyoid and
stapedial arteries.
Tanoue, Shuichi & Kiyosue, Hiro &
Mori, Hiromu & Hori, Yuzo &
Okahara, Mika & Sagara, Yoshiko.
(2013). Maxillary Artery: Functional
and Imaging Anatomy for Safe and
Effective Transcatheter Treatment.
Radiographics : a review publication
of the Radiological Society of North
America, Inc. 33. e209-24.
10.1148/rg.337125173.

19.  The stapedial artery passes through
the ring of the stapes and divides
into supraorbital, infraorbital, and
mandibular branches which follow
the three divisions of the trigeminal
nerve. The infraorbital and
mandibular branches arise from a
common stem, the terminal part of
which anastomoses with
the external carotid artery.
 On the obliteration of the stapedial
artery, this anastomosis enlarges
and forms the internal maxillary
artery
 The common stem of the
infraorbital and mandibular
branches passes between the two
roots of the auriculotemporal
nerve and becomes the middle
meningeal artery
 the original supraorbital branch of
the stapedial is represented by the
orbital twigs of the middle
meningeal.
The Persistent Stapedial Artery
Richard Silbergleit, Douglas J. Quint, Bharat A. Mehta, Suresh C. Patel, Joseph J. Metes and Samir E. Noujaim
American Journal of Neuroradiology March 2000, 21 (3) 572-577

20. Third & Fourth Arch Artery
 In the 29-day embryo, the first and second aortic arches have disappeared
 The third, fourth, and sixth arches are large.
 The conotruncal region has divided so that the sixth arches are now continuous
with the pulmonary trunk.
Langman’s Embryology, 12th ed

22.  The third aortic arch forms the common
carotid artery and
 The first part of the The external carotid
artery is a sprout of the third aortic arch.
 Fourth Arch Artery: On the left, it forms part
of the arch of the aorta, between the left
common carotid and the left subclavian
arteries.
 On the right, it forms the most proximal
segment of the right subclavian artery,

23. 6th Aortic Arch
 also known as the pulmonary arch
 On the right side, the proximal part becomes the proximal segment of the right pulmonary artery.
 On the left, the distal part persists during intrauterine life as the ductus arteriosus
Fig. 4.2 (a) Cardiac neural crest cells (CNCCs) in the outflow
cushions. Cross-section through the distal and middle outflow
tract shows position of the condensed CNCC-derived
mesenchyme within the cushions to form the future aorta (a)
and pulmonary trunk (p). (b) Stages of outflow septation in the
chick. (a) U-shaped septation complex straddles the aortic sac
between the 4th and 6th aortic arch arteries. (b) The septation
complex grows at the expense of the prongs. (c) Septation of
the conus (Adapted from Hutson and Kirby

25. Somatic arteries (Intersegmental)
 Each primitive dorsal aorta gives off somatic arteries
(intersegmental branches to the body wall)
 posterior intercostal, subcostal and lumbar arteries
Gray’s Anatomy. 41st ed

26. Early umbilical arteries
 Direct caudal continuation of the primitive dorsal
aortae.
 They are present in the body stalk before any
vitelline or visceral branches emerge.
 After the dorsal aortae fuse, the umbilical
arteries arise from their ventrolateral aspects
 Later, the proximal part of each umbilical artery
is joined by a new vessel, that leaves the aorta
at its termination.
 This, possibly the fifth lumbar intersegmental
artery, constitutes the dorsal root of the
umbilical artery (the original stem, the ventral
root).
 The dorsal root gives off the axial artery of the
lower limb, branches to the pelvic viscera and,
more proximally, the external iliac artery.
 The ventral root disappears entirely, and the
umbilical artery now arises from that part of its
dorsal root distal to the external iliac artery, i.e.
the internal iliac artery
Henry Gray (1918) Anatomy of the Human Body

27. Adult derivatives of umbilical
arteries
 medial umbilical ligament
 a branch of the anterior division of
the internal iliac artery.
 gives rise to the superior vesical
arteries.

28. Lateral splanchnic arteries
 the mesonephros, metanephros,
 testis or ovary
 the suprarenal gland.
Diagrams showing arterial mesonephric blood supply
and its relationship to eventual metanephros in a 4–6-
week embryo and 8–10-week embryo. SMA: Superior
mesenteric artery, IMA: inferior mesenteric artery, 1:
cranial group mesonephric arteries, 2: middle group
mesonephric arteries, RG: reproductive gland, MSN:
mesonephros, MTN: metanephros, RAU: rete arteriosum
urogenitale, SMA: superior mesenteric artery, IMA:
inferior mesenteric artery, GA: gonadal artery, AG:
adrenal gland, AA: adrenal artery, MTN: metanephros,
RA: renal artery, PAA: polar accessory artery. The
adrenal artery usually develops from the cranial group
of mesonephric arteries whereas the gonadal artery
forms from arteries of the caudal group (RAU). The
definite renal artery comes either from the last branch of
the middle group or the first of the caudal group.
Persisting mesonephric arteries form accessory vessels
(PAA) as shown in the example

29. Ventral splanchnic arteries
 Distributed to the capillary plexus in the
wall of the yolk sac.
 After fusion of the dorsal aortae, they
merge as unpaired trunks.
 dorsal and ventral splanchnic anastomoses
 reduced to three, the coeliac trunk and the
superior and inferior mesenteric arteries
 above the diaphragm, a variable number
of ventral splanchnic arteries persist,
usually four or five, supplying the thoracic
oesophagus.
 The dorsal splanchnic anastomosis persists
in the gastroepiploic, pancreaticoduodenal
and primary branches of the colic arteries
 the ventral splanchnic anastomosis forms
the right and left gastric and the hepatic
arteries
Gray’s Anatomy. 41st ed

30.  derived from two sources:
 (1) angioblasts formed
from sprouts off the sinus
venosus that are
distributed over the heart
surface by cell migration
 (2) the epicardium itself.
 Neural crest cells also
contribute smooth muscle
cells along the proximal
segments of these arteries.
 Connection of the coronary
arteries to the aorta occurs
by ingrowth of arterial
endothelial cells from the
arteries into the aorta.
Coronary Arteries
Fig. 5.2 Embryologic development of coronary vasculature (From Lluri
and Aboulhosn)

31. Arterial System Defects

33. Coarctation of Aorta
 Preductal
 Postductal

34. Abnormal Right Subclavian

35. Double aortic arch

36. Interrupted aortic arch

38. Common brachiocephalic trunk

39. Variant Origin of Vertebral
Arteries

42. Pulmonary Sequestration

43. Thank You!!!