Cardiovascular System - Blood Vessel Development

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Introduction

Developing Blood Vessel

Blood develops initially within the core of "blood islands" in the mesoderm. During development, there follows a series of "relocations" of the stem cells to different organs within the embryo. In the adult, these stem cells are located in the bone marrow. At the time when blood first forms, there are no bones!

Note that blood vessel development is tightly coupled to development of other systems for example: osteogenesis (bone formation) that is dependent upon early capillary formation; endocrine development that requires blood vessels for hormone distribution.

Vasculogenesis Angiogenesis
formation of new blood vessels
(endothelium from mesoderm)
formation of blood vessels from pre-existing vessels
(occurs in development and adult)

Angioblasts initially form small cell clusters (blood islands) within the embryonic and extraembryonic mesoderm. These blood islands extend and fuse together making a primordial vascular network. Within these islands the peripheral cells form endothelial cells while the core cells form blood cells (haemocytoblasts).

Recent work has shown that the formation of the initial endothelial tube is by a process of coalescence of cellular vacuoles within the developing endothelial cells, which fuse together without cytoplasmic mixing to form the blood vessel lumen.


See also the related pages Arterial Development, Venous Development, Placental Villi Blood Vessels and Coronary Circulation Development.

Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer


Developmental Signals - Vascular Endothelial Growth Factor | Smooth Muscle Development

Some Recent Findings

Adult human cardiovascular system
  • Cell-matrix signals specify bone endothelial cells during developmental osteogenesis[1] “Blood vessels in the mammalian skeletal system control bone formation and support haematopoiesis by generating local niche environments. Here, we report that embryonic and early postnatal long bone contains a specialized endothelial cell subtype, termed type E, which strongly supports osteoblast lineage cells and later gives rise to other endothelial cell subpopulations. The differentiation and functional properties of bone endothelial cells require cell-matrix signalling interactions." Bone Development | INTEGRIN BETA-1
  • Endothelium in the pharyngeal arches 3, 4 and 6 is derived from the second heart field[2] "Oxygenated blood from the heart is directed into the systemic circulation through the aortic arch arteries (AAAs). The AAAs arise by remodeling of three symmetrical pairs of pharyngeal arch arteries (PAAs), which connect the heart with the paired dorsal aortae at mid-gestation. Aberrant PAA formation results in defects frequently observed in patients with lethal congenital heart disease. How the PAAs form in mammals is not understood. The work presented in this manuscript shows that the second heart field (SHF) is the major source of progenitors giving rise to the endothelium of the pharyngeal arches 3 - 6, while the endothelium in the pharyngeal arches 1 and 2 is derived from a different source. During the formation of the PAAs 3 - 6, endothelial progenitors in the SHF extend cellular processes toward the pharyngeal endoderm, migrate from the SHF and assemble into a uniform vascular plexus. This plexus then undergoes remodeling, whereby plexus endothelial cells coalesce into a large PAA in each pharyngeal arch."
  • Review - The Molecular Regulation of Arteriovenous Specification and Maintenance[3] "The formation of a hierarchical vascular network, composed of arteries, veins and capillaries, is essential for embryogenesis and is required for the production of new functional vasculature in the adult. Elucidating the molecular mechanisms that orchestrate the differentiation of vascular endothelial cells into arterial and venous cell fates is requisite for regenerative medicine, as the directed formation of perfused vessels is desirable in a myriad of pathological settings, such as in diabetes and following myocardial infarction. Additionally, this knowledge will enhance our understanding and treatment of vascular anomalies, such as arteriovenous malformations (AVMs). From studies in vertebrate model organisms, such as mouse, zebrafish and chick, a number of key signaling pathways have been elucidated that are required for the establishment and maintenance of arterial and venous fates. These include the Hedgehog, Vascular Endothelial Growth Factor (VEGF), Transforming Growth Factor-β (TGF-β), Wnt and Notch signaling pathways. In addition, a variety of transcription factor families acting downstream of-or in concert with-these signaling networks play vital roles in arteriovenous (AV) specification. These include Notch and Notch-regulated transcription factors (e.g. HEY and HES), SOX factors, Forkhead factors, β-Catenin, ETS factors and COUP-TFII. It is becoming apparent that AV specification is a highly coordinated process that involves the intersection and carefully orchestrated activity of multiple signaling cascades and transcriptional networks."
More recent papers  
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Search term: Blood Vessel Embryology

<pubmed limit=5>Blood Vessel Embryology</pubmed>

Older papers  
  • Specification of arterial, venous, and lymphatic endothelial cells during embryonic development [4] "The groundbreaking discovery about arterial and venous expression of ephrinB2 and EphB4, respectively, in early embryonic development has led to a new paradigm for vascular research, providing compelling evidence that arterial and venous endothelial cells are established by genetic mechanisms before circulation begins. For arterial specification, vascular endothelial growth factor (VEGF) induces expression of Notch signaling genes, including Notch1 and its ligand, Delta-like 4 (Dll4), and Foxc1 and Foxc2 transcription factors directly regulate Dll4 expression. Upon activation of Notch signaling, the Notch downstream genes, Hey1/2 in mice or gridlock in zebrafish, further promote arterial differentiation. On the other hand, the orphan nuclear receptor COUP-TFII is a determinant factor for venous specification by inhibiting expression of arterial specific genes, including Nrp1 and Notch. After arterial and venous endothelial cells differentiate, a subpopulation of venous endothelial cells is thought to become competent to acquire lymphatic endothelial cell fate by progressively expressing the transcription factors Sox18 and Prox1 to differentiate into lymphatic endothelial cells."
  • Developmental origin of smooth muscle cells in the descending aorta in mice[5] "Aortic smooth muscle cells (SMCs) have been proposed to derive from lateral plate mesoderm. ....(these results) suggested that all SMCs in the adult descending aorta derive from the somites, whereas no contribution was recorded from lateral plate mesoderm."
  • Notch ligand Jagged1 is required for vascular smooth muscle development[6] "The Notch ligand Jagged1 (Jag1) is essential for vascular remodeling. ...Jag1 null phenotype. These embryos show striking deficits in vascular smooth muscle, whereas endothelial Notch activation and arterial-venous differentiation appear normal."

Endothelial Progenitors

Recent work has shown that the formation of the initial endothelial tube is by a process of coalescence of cellular vacuoles within the developing endothelial cells, which fuse together without cytoplasmic mixing to form the blood vessel lumen. [7]

Endothelial Tube Formation

Blood vessel lumen formation cartoon

Blood vessel lumen formation

Vessel Specification

Embryonic Circulations

The following data is from a recent review.[4]

Arterial Specification

Factor Function
Shh Loss of Shh results in lack of arterial identity in zebrafish. Shh acts upstream of VEGF.
VEGF VEGF acts downstream of Shh signaling to activate Notch via the PLCγ/ERK pathway in zebrafish. Mutant mice expressing only VEGF188 lack arterial differentiation.
Nrp1 Null mice display impaired arterial differentiation. Nrp1 is involved in a positive feedback loop of VEGF signaling.
Notch Notch acts downstream of Shh and VEGF signaling in zebrafish. Notch1; Notch4 mutant mice have abnormal vascular development.
Dll4 Null mice lack arterial specification.
Dll1 Null mice fail to maintain arterial identity.
Hey1/2 (Grl) Null mice lack arterial specification. Lack of grl in zebrafish results in loss of arterial specification.
Foxc1/c2 Foxc1; Foxc2 mutant mice lack arterial specification. Foxc1 and Foxc2 directly regulate Dll4 and Hey2 expression. Foxc1 and Foxc2 are also involved in lymphatic vessel development.
Sox7/18 Lack of Sox7/18 results in loss of arterial identity in zebrafish.
Snrk-1 Snrk-1 acts downstream or parallel to Notch signaling in zebrafish.
Dep1 Dep1 acts upstream of PI3K in arterial specification in zebrafish.
Crlr Shh regulates VEGF activity by controlling crlr expression in zebrafish.
EphrinB2 Null mice lack boundaries between arteries and veins. EphrinB2 is involved in lymphatic vascular remodeling and maturation.

Venous Specification

Factor Function
COUP-TFII COUP-TFII suppresses arterial cell fate by inhibiting Nrp1 and Notch. COUP-TFII also interacts with Prox1 to regulate lymphatic gene expression.
EphB4 Null mice lack boundaries between arteries and veins.

Lymphatic Specification

Factor Function
Sox18 Null mice fail to specify lymphatic endothelial cells. Sox18 induces Prox1 expression.
Prox1 Prox1 induces lymphatic markers and maintains lymphatic cell identity.

Vascular Endothelial Growth Factor

Growing blood vessels follow a gradient generated by tagret tissues/regions of Vascular Endothelial Growth Factor (VEGF) to establish a vascular bed. Recent findings suggest that 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.

Notch and yolk sac blood vessels model.jpg Vascular formation cartoon1.jpg
Notch and yolk sac blood vessels model[8] Vasculogenesis and angiogenesis[9]


Links: OMIM - VEGFA | OMIM - Notch

Regulators of Growth

The following data is from a review article on ovary vascular development.[10]

Stimulators of Angiogenisis

  • Peptide growth factors
    • Vascular endothelial growth factor-Aa,b, -Bb, -Cb, -D
    • [-E], -F (VEGF-Aa,b, -Bb, -Cb, -Db, -E, -F)
    • Placenta growth factor (PlGF)
    • Angiopoietin-1 (Ang-1)
    • Angiopoietin-2 (Ang-2) [modulator in the presence of angiogenic activity]
    • Acidic fibroblast growth factor (FGF-1)
    • Basic fibroblast growth factor (FGF-2)
    • Platelet-derived growth factor (PDGF)
    • Transforming growth factor-a (TGF-a)
    • Transforming growth factor-b (TGF-b)
    • Hepatocyte growth factor (HGF)
    • Insulin-like growth factor-I (IGF-I)
  • Multifunctional cytokines/immune mediators
    • Tumour necrosis factor-a (low-dose)
    • Monocyte chemoattractant protein-1 (MCP-1)
  • CXC-chemokines
    • Interleukin-8 (IL-8)
  • Enzymes
    • Platelet-derived endothelial cell growth factor
    • (PD-ECGF; thymidine phosphorylase)
  • Angiogenin (ribonuclease A homologue)
  • Hormones
    • Oestrogens
    • Prostaglandin-E1, -E2
    • Follistatin
    • Proliferin
  • Oligosaccharides
    • Hyaluronan oligosaccharides
    • Gangliosides

Inhibitors of Angiogenisis

  • Peptide growth factors and proteolytic peptides
    • Angiopoietin-2 (Ang-2) [in the absence of angiogenic activity]
    • Angiostatin
    • Endostatin
    • 16 kDa prolactin fragment
    • Laminin peptides
    • Fibronectin peptides
  • Inhibitors of enzymatic activity
    • Tissue metalloproteinase inhibitors
    • (TIMP-1, -2, -3, -4)
    • Plasminogen activator inhibitors
    • (PAI-1, -2)
  • Multifunctional cytokines/immune mediators
    • Tumour necrosis factor-a (high-dose)
    • Interferons
    • Interleukin-12
  • CXC-chemokines
    • Platelet factor-4 (PF-4)
    • Interferon-gamma-inducible protein-10 (IP-10)
    • Gro-beta
  • Extracellular matrix molecules
    • Thrombospondin
  • Hormones/metabolites
    • 2-Methoxyestradiol (2-ME)
    • Proliferin-related protein
  • Oligosaccharides
    • Hyaluronan, high-molecular-weight species

Histology

Vein Light Microscopy

Vein histology 01.jpg

The entire developing and adult cardiovascular system (blood vessels and heart) is lined by a simple squamous epithelium. (Stain - Haematoxylin Eosin)


Capillaries

Type H

A developmental capillary endothelial cell subtype associated with osteogenesis, located at the metaphysis and endosteum of postnatal long bone, that couples angiogenesis with osteogenesis. This endothelial cell subtype expresses the markers CD31/PECAM1 and endomucin (CD31hi Emcnhi).


Type E

A newly identified endothelial cell subtype similar to type H in function, supporting osteoblast lineage cells and then gives rise to other endothelial cell subpopulations, but this subtype is found in embryonic and early postnatal long bone.[1]


Electron Micrographs

Blood capillary EM 04.jpg

Arteries

Cardiac Blood Vessels

Earliest vessels in the heart wall develop subepicardially (beneath the outside surface of the heart) near the apex at Carnegie stage 15, which then extends centripetally and at stage 17 coronary arterial stems communicate with the aortic lumen.[12]

Abnormalities

Due to the extensive embryonic, and ongoing, remodelling of the vascular system, there are many different vascular variations and anomalies.

Neural

Trigeminal artery 01.jpg

Persistent trigeminal and hypoglossal arteries[13]


Links: Cerebrum Development | Head Development

References

  1. 1.0 1.1 <pubmed>28218908</pubmed>
  2. <pubmed>27955943</pubmed>
  3. <pubmed>25641373</pubmed>
  4. 4.0 4.1 <pubmed>20238301</pubmed>| PMC2899674
  5. <pubmed>18417617</pubmed>
  6. <pubmed>18245384</pubmed>
  7. <pubmed>11827993</pubmed>
  8. <pubmed>21352545</pubmed>| BMC Dev Biol.
  9. <pubmed>21537463</pubmed>
  10. <pubmed>11141338</pubmed>
  11. <pubmed>21702933</pubmed>| PMC3141733 | BMC Cell Biol.
  12. <pubmed>8915616</pubmed>
  13. <pubmed>26060802</pubmed>| J Stroke.

Reviews

<pubmed></pubmed> <pubmed></pubmed> <pubmed>25641373</pubmed>


Articles

<pubmed></pubmed> <pubmed></pubmed> <pubmed>10948449</pubmed> <pubmed>12406884</pubmed>

Search Pubmed

Click on the listed keywords below (used to search the external database) the most current references on Medline will be displayed.

Search Pubmed: Blood Vessel Development | Blood Vessel embryology | Blood Vessel smooth muscle Development | Blood Vessel smooth muscle Development

Terms

  • cerebroplacental ratio - (CPR) measured by doppler ultrasound, the ratio between the middle cerebral artery pulsatility index (PI) MoM and the umbilical artery PI. A potential predictor of adverse pregnancy outcome.
  • pulsatility index - (PI) systolic peak velocity/diastolic peak velocity)/velocity time integral
  • resistance index - (RI) systolic peak velocity/diastolic peak velocity)/systolic peak velocity
  • S/D - systolic/diastolic ratio
Placenta Terms (expand to view) 
  • after-birth - term used to describe the delivery of placenta and placental membranes following birth of the child.
  • allantois - An extraembryonic membrane, endoderm in origin extension from the early hindgut, then cloaca into the connecting stalk of placental animals, connected to the superior end of developing bladder. In reptiles and birds, acts as a reservoir for wastes and mediates gas exchange. In mammals is associated/incorporated with connecting stalk/placental cord fetal-maternal interface.
  • amniocentesis - Clinical term for a prenatal diagnostic test where an ultrasound guided needle is used to extract a sample of the amniotic fluid. Amniocentesis
  • anastomosis - Term used to describe the connection between two tubes. Applied to describe the connection between peripheral blood vessels without an intervening capillary bed.
  • anchoring villi - (stem villi) describes the placental villi (embryonic) that attach to the decidua (maternal) tissue. The tip of the villi consists of a column of trophoblast cells attached to an epithelial plaque.
  • angioblasts form clusters or blood islands on surface of yolk sac.
  • angiogenesis - Term describing the development of new vessels from already existing vessels, this process is secondary to vasculogenesis which is the initial formation of first blood vessels by differentiation of pluripotent mesenchymal cells (extraembryonic mesoderm).
  • capsularis - portion of maternal decidua that covers the conceptus facing towards the uterine cavity.
  • cerebroplacental ratio - (CPR) a doppler ultrasound measurement calculated as the simple ratio between the middle cerebral artery pulsatility index (MCA‐PI) and the umbilical artery pulsatility index (UA‐PI). Fetuses with an abnormal ratio are thought to be a predictor of adverse pregnancy outcome.
  • chorioamnionitis - (CA) An intraamniotic puerperal infection described as having 3 forms: histologic, clinical (clinical chorioamnionitis, IAI), and subclinical. Intraamniotic infection is a common (2-4%) event in labor and the systemic inflammatory response can also lead to preterm birth and neonatal complications.
  • chorion - The extraembryonic membrane generated from trophoblast and extraembryonic mesoderm that forms placenta. chorion and amnion are made by the somatopleure. The chorion becomes incorporated into placental development. The avian and reptilian chorion lies beside the egg shell and allows gas exchange.
  • chorionic cavity - The fluid-filled extraembryonic coelom (cavity) formed initially from trophoblast and extraembryonic mesoderm that forms placenta. chorion and amnion are made by the somatopleure. The chorion becomes incorporated into placental development. The avian and reptilian chorion lies beside the egg shell and allows gas exchange. In humans, this cavity is lost during week 8 when the amniotic cavity expands and fuses with the chorion.
  • chorion frondosum - (frondosum = leafy) The chorion found on conceptus oriented towards maternal blood supply where the majority of villi form and proliferate, will contribute the fetal component of the future placenta.
  • chorion laeve - (laeve = smooth) The smooth chorion found on conceptus away from maternal blood supply (towards uterine epithelium and cavity) with very few villi present.
  • chorionic somatomammotropin - (CSH, human lactogen) A hormone synthesized within the placenta by syncytiotrophoblast cells. This protein hormone (190 amino acid) has a structure is similar to pituitary growth hormone.
  • chorionic villus sampling - (CVS) The taking a biopsy of the placenta, usually at the end of the second month of pregnancy, to test the fetus for genetic abnormalities.
  • coelocentesis - A sampling of extracoelomic fluid usually for an early prenatal diagnostic technique.
  • connecting stalk - the original extra-embryonic mesoderm structure attaching the embryonic disc to the chorion. The placental blood vessels form within this structure.
  • cord blood - (human umbilical cord blood, HUCB) A term used to describe blood collected from the placenta usually after birth. Has been identified as a source of stem cells with potential therapeutic uses and is stored in Cord Blood Banks throughout the world.
  • cord knotting Term describing umbilical or placental cord knotting. This occurs in about 1% prevents the passage of placental blood, pseudoknots also occur usually with no effect.
  • cord presentation - A term used to describe at birth the presence of the umbilical cord between the fetal presenting part and the cervix, with or without membrane rupture.
  • cord prolapse - A term used to describe at birth the descent of the umbilical cord through the cervix alongside (occult) or past (overt) the presenting part in the presence of ruptured membranes (incidence of 0.1% to 0.6%).
  • cotyledon - (Greek, kotyle = a deep cup) In the embryos of seed plants, the "seed leaves," in which nutrients are stored for use after germination. In placental animals, the term is also to describe the leaf-like structure of the placenta surface.
  • cytotrophoblast - The "cellular" trophoblast layer surrounding (forming a "shell") the early implanting conceptus. Beginning at uterine adplantation, proliferation and fusion of these cells is thought to form a second outer trophoblast layer, the syncytiotrophoblast. The cytotrophoblast layer contributes to formation of the placental villi, the functional component of the fetal placenta.
  • decidua basalis - The term given to the uterine endometrium at the site of implantation where signaling transforms the uterine stromal cells (fibroblast-like) into decidual cells. This forms the maternal component of the placenta, the decidualization process gradually spreads through the remainder of the uterus, forming the decidua parietalis.
  • decidua basalis reaction - Term describing the maternal endometrial changes that occur initially at the site of, and following, blastocyst implantation. Seen as a deposition of glycogen, fibrin and proliferation of blood vessels. See also decidualization.
  • decidua capsularis - The term given to the uterine endometrium which has been converted to decidua surrounding the conceptus on the smooth chorion side.
  • decidua parietalis - The term given to the remainder of the uterine endometrium, away from the site of implantation, that gradually becomes comverted to decidua.
  • decidual cell - The uterine stromal cells (fibroblast-like) that differentiate in response to both steroid hormones (progesterone) and embryonic signals. These cells then alter uterine environment to support further embryonic development as well as producing cytokines related to prolactin (PRL) and have an innate immune function.
  • decidual reaction - maternal endometrial reaction invoked in order to block the rapid extension of the implanting syncytium.
  • decidualization - (decidualisation, decidual reaction) The process by which uterine stromal cells differentiate in response to both steroid hormones and embryonic signals into large epitheliod decidual cells. This process is essential for the progress of implantation and establishing fetal-maternal communication.
  • DHEA - (dehydroepiandrosterone, androstenolone) precursor of sex steroid hormones and is converted to testosterone and estradiol. Postnatally, an abundant circulating steroid produced in the adrenal gland. The fetal adrenal cortex produces dehydroepiandrosterone sulfate (DHEA-S) used by the placenta to produce estrogens. DHEA, androstenedione, and testosterone can be metabolized to epiandrosterone, and etiocholanolone. PMID 15635500
  • fetal drug addiction - occurs when drugs used maternally cross the placental barrier and can establish neural/physiological addiction in the unborn fetus. drugs
  • fetal erythroblastosis - (Haemolytic Disease of the Newborn) A clinical term describing an immune response between fetal and maternal blood groups; from fetus Rh+ / maternal Rh-. The leakage of blood from fetus, particularly at birth, causes maternal anti-Rh antibodies, which is then dangerous for a 2nd or future pregnancies.
  • fetal intra-abdominal umbilical vein varix - (FIUV, umbilical vein varix) focal dilatation of the umbilical venous diameter at the level of cord insertion, the dilatation diameter increases linearly with gestational age. Represent about 4% of umbilical cord abnormalities

with an incidence of about 2.8 per 1,000 pregnancies, there is also a rarer form of extra-abdominal varices.PMID 24883288

  • fibrinoid layer - (Nitabuch's layer) A layer formed at maternal/fetal interface during placentation and is thought to act to prevent excessively deep conceptus implantation. Fibrin-type fibrinoid (maternal blood-clot product) and matrix-type fibrinoid (secreted by invasive extravillous trophoblast cells).
  • floating chorionic villi - Term used to describe the placental microanatomy structure of chorionic villi that are not attached to the maternal decidua and float in the maternal blood-filled space (lacunae). Structurally the same as anchoring chorionic villi conceptus side that are attached to the maternal decidua.These villi go through the same stages of development: primary villi - secondary villi - tertiary villi
  • hemotrophic nutrition - Term used to describe in late placenta development the transfer of blood-borne nutrition from maternal to embryo/fetuscompared to early histiotrophic nutrition.
  • heterotopic pregnancy - (Greek, heteros = other) Clinical term for a very rare pregnancy of two or more embryos, consisting of both a uterine cavity embryo implantation and an ectopic implantation.
  • histiotrophic nutrition - Term used to describe in early placenta development the intital transfer of nutrition from maternal to embryo (histiotrophic nutrition) compared to later blood-borne nutrition (hemotrophic nutrition). Histotroph is the nutritional material accumulated in spaces between the maternal and fetal tissues, derived from the maternal endometrium and the uterine glands. This nutritional material is absorbed by phagocytosis initially by blastocyst trophectoderm and then by trophoblast of the placenta. in later placental development nutrition is by the exchange of blood-borne materials between the maternal and fetal circulations, hemotrophic nutrition.
  • Hofbauer cells - Cells found within placental villi connective tissue. Have a role as macrophages of mesenchymal origin with potentially additional functions (remodeling, vasculogenesis, regulation of stromal water content).
  • Human chorionic corticotropin - (hCACTH) placental derived hormone equivilant to corticotropin (ACTH) from the pituitary.
  • Human chorionic gonadotrophin - (hCG) like leutenizing hormone, supports corpus luteum, originally secreted by trophoblast cells.
  • Human chorionic somatommotropin - (hCS, placental lactogen) hormone level increases in maternal blood through pregnancy, decreases maternal insulin sensitivity (raising maternal blood glucose levels and decreasing maternal glucose utilization) aiding fetal nutrition.
  • Template:Hydatiform mole - A uterine tumour with "grape-like" placenta appearance without enclosed embryo formation, arises mainly from a haploid sperm fertilizing an egg without a female pronucleus. It is one form of gestational trophoblastic disease(GTD), a number of abnormalities including hydatiform mole, invasive mole, choriocarcinoma and placental site trophoblastic tumor (PSTT).
  • hysterectomy – clinical term for the surgical removal of the uterus.
  • Langhans layer - cytotrophoblast cell layer.
  • maternal antibodies - antibodies from the mother's immune system that are capable of crossing placental barrier. They can provide immune protection to the embryo, but may also participate in immune disease (fetal erythroblastosis).
  • maternal sinusoids - placental spaces around chorionic villi that are filled with maternal blood. This is the closest maternal/fetal exchange site.
  • Nitabuch's layer - (fibrinoid layer) The layer formed at maternal/fetal interface during placentation and is thought to act to prevent excessively deep conceptus implantation. Fibrin-type fibrinoid (maternal blood-clot product) and matrix-type fibrinoid (secreted by invasive extravillous trophoblast cells).
  • Morbidly adherent placenta (MAP) A general clinical term used to describe the different forms of abnormal placental implantation (Accreta, Increta and Percreta).
  • oligohydramnios - Clinical term for the accumulation a deficiency of amniotic fluid during pregnancy. See also polyhydramnios, an excess of amniotic fluid.
  • persistent right umbilical vein - (PRUV) A placental cord abnormality associated with fetal abnormalities and poor neonatal prognosis. The estimated incidence of persistent right umbilical vein in a low-risk population is 1 : 526. PMID 12047534
  • polyhydramnios - Clinical term for the accumulation of excess amniotic fluid during pregnancy. See also oligohydramnios, a deficiency of amniotic fluid.
  • placenta - (Greek, plakuos = flat cake) The developmental organ formed from maternal and fetal contributions in animals with placental development. In human, the placenta at term is a discoid shape "flat cake" shape; 20 cm diameter, 3 cm thick and weighs 500-600 gm. Placenta are classified by the number of layers between maternal and fetal blood (Haemochorial, Endotheliochorial and Epitheliochorial) and shape (Discoid, Zonary, Cotyledenary and Diffuse). The placenta has many different functions including metabolism, transport and endocrine.
  • placenta accreta - The abnormal placental adherence, either in whole or in part of the placenta with absence of decidua basalis, leading to retention as an after-birth to the underlying uterine wall. The incidence of placenta accreta also significantly increases in women with previous cesarean section compared to those without a prior surgical delivery.
  • placental arteries - (umbilical arteries) In placental animals, the blood vessels which develop within the placental cord carrying relatively deoxygenated blood from the embryo/fetus to the placenta. In humans, there are two placental arteries continuous with the paired internal iliac arteries (hypogastric arteries) arising off the dorsal aortas. At birth this vessel regresses and form the remnant medial umbilical ligament.
  • placental cord - (umbilical cord) The placental cord is the structure connecting the embryo/fetus to the placenta. It is initially extra-embryonic mesoderm forming the connecting stalk within which the placental blood vessels (arteries and veins) form. In human placental cords the placental blood vessels are initially paired, later in development only a single placental vein remains with a pair of placental arteries. This structure also contains the allantois, an extension from the hindgut cloaca then urogenital sinus. Blood collected from the placental cord following delivery is a source of cord blood stem cells.)
  • placental diameter - is measured in the transverse section by calculating the maximum dimensions of the chorionic surface.
  • placental growth factor - (PlGF) A growth factor of the vascular endothelial growth factor (VEGF) family, released from the placental trophoblast cells and other sources that stimulates blood vessel growth.
  • placental malaria - The malarial infection of the placenta by sequestration of the infected red blood cells. This condition can be common in regions where malaria is endemic with women carrying their first pregnancy (primigravida).
  • placenta membranacea - rare placental abnormality characterized by the presence of chorionic villi directly attached to and covering the fetal membranes. Placenta Membranacea
  • placenta previa - placenta overlies internal os of uterus, abnormal bleeding, may require cesarian delivery.
  • placental thickness - is measured at its mid-portion from the chorionic plate to the basilar plate, on a longitudinal plane (less than 4 cm at term). Excludes any abnormalities (fibroids, myometrial contractions, or venous lakes). The placental thickness approximates in millimeters to the weeks of gestation.
  • placental vein - (umbilical vein) In placental animals, the blood vessels which develop within the placental cord carrying relatively oxygenated blood from the placenta to the embryo/fetus. In humans, there are initially two placental veins which fuse to form a single vein. The resence of paired veins in the placental cord can be indicative of developmental abnormalities.
  • placentophagia - Term used to descrbe the maternal ingestion of afterbirth materials (placental membranes and amniotic fluid) that can occur following mammalian parturition (birth).
  • primary villi - (primary chorionic villi) Term describing the earliest stage of embryonic placenta development. In humans, the conceptus during week 2 this first stage of chorionic villi development consists of only the trophoblastic shell cells (syncitiotrophoblasts and cytotrophoblasts) forming finger-like extensions into maternal decidua. Initially these finger-like projections cover the entire surface of chorionic sac and later become restricted to the placental surface. The villi stages are ongoing as the placenta continues to grow through both the embryonic and fetal development.
  • pre-eclampsia - During pregnancy a combination of high blood pressure, protein in urine and fluid retention resulting in maternal sudden excessive swelling of the face, hands and feet. Eclampsia is the subsequent development of convulsions, kidney failure, liver failure, clotting problems or mortality.
  • Rh alloimmunization - feto-maternal haemorrhage generally in late pregnancy results in an Rh-negative woman becoming sensitised to Rh-positive fetal cells that enter her circulation. Clinically treated with anti-D immune globulin prophylaxis, alloimmunization occurs in 9–10% of at-risk pregnancies. immune
  • secondary villi - (secondary chorionic villi) Term describing the second stage of embryonic placenta development. In humans, the conceptus during week 3 onward this stage of chorionic villi development consists of the trophoblastic shell cells (syncytiotrophoblast and cytotrophoblasts) filled with extraembryonic mesoderm forming finger-like extensions into maternal decidua. Initially these finger-like projections cover the entire surface of chorionic sac and later become restricted to the placental surface. The villi stages are ongoing as the placenta continues to grow through both the embryonic and fetal development. Placental villi stages: primary villi - secondary villi - tertiary villi
  • syncytiotrophoblast - A multinucleated cell currently thought to form by the fusion of another trophoblast cell the cytotrophoblasts, within the trophoblast layer (shell) of the implanting conceptus. In early development, these cells mediate implantation of the conceptus into the uterine wall and secrete the hormone (Template:Human Chorionic Gonadotrophin, hCG) responsible for feedback maintainance of the corpus luteum (in maternal ovary) and therefore maintaining early pregnancy.
  • trophoblast - (trophectoderm, Greek, trophe = "nutrition" and blast = a primordial cell) cells that firstly support adplantation, implantation and endocrine support of pregnancy. Contribute to the extraembryonic tissues, fetal placenta and membranes. Initially form 2 populations individual cytotrophoblast cells and their fused multinucleate syncytiotrophoblast cells.
  • Twin-twin transfusion syndrome - (TTTS) in monozygotic twins with monochorionic and diamniotic placenta, with intrauterine blood transfusion from one twin (donor) to another twin (recipient) where there is an imbalance of blood flow from the donor twin to the recipient twin. Clinically diagnosed by the alternate presence of polyhydramnios in one fetus and oligohydramnios in the co-twin, occurs in about 10% of monochorionic twins.
  • umbilical cord (placental cord) fetal attachment cord 1-2 cm diameter, 30-90cm long, covered with amniotic attached to chorionic plate, umbilical vessels (artery, vein) branch into chorionic vessels. Vessels anastomose within the placenta.
  • umbilical vein varix - (fetal intra-abdominal umbilical vein varix, FIUV) focal dilatation of the umbilical venous diameter at the level of cord insertion, the dilatation diameter increases linearly with gestational age. Represent about 4% of umbilical cord abnormalities

with an incidence of about 2.8 per 1,000 pregnancies, there is also a rarer form of extra-abdominal varices. PMID 24883288

  • vasculogenesis - formation of first blood vessels by differentiation of pluripotent mesenchymal cells (extraembryonic mesoderm) followed by angiogenesis which is the development of new vessels from already existing vessels.
  • vasculosyncytial membranes - localised areas of the placental villous membrane where the barrier thickness separating maternal and fetal circulations is reduced to as little as 1-2 microns. PMID 1287078
  • villi - Plural of villus, which is a thin projection from a surface. The term in development is used to describe the individual functional units together of the fetal placenta.
  • virus - small infectious agents that may cross the placental barrier. Can infect embryo and/or placenta and cause developmental abnormalities. (e.g. cytomegalovirus, rubella, measles).
  • Wharton's jelly - placental cord (umbilical cord) gelatinous connective tissue composed of myofibroblast-like stromal cells, collagen fibers, and proteoglycans. Increases in volume (myxomatous, connective tissue embedded in mucus) at parturition (birth) to assist closure of placental blood vessels. Matrix cells from Wharton's jelly have recently been identified as a potential source of mesenchymal stem cells (MSC), also called mesenchymal stromal cell. This placental cord substance is named after Thomas Wharton (1614-1673) an English physician and anatomist who first described this placental tissue.
Other Terms Lists  
Terms Lists: ART | Birth | Bone | Cardiovascular | Cell Division | Endocrine | Gastrointestinal | Genital | Genetic | Head | Hearing | Heart | Immune | Integumentary | Neonatal | Neural | Oocyte | Palate | Placenta | Radiation | Renal | Respiratory | Spermatozoa | Statistics | Tooth | Ultrasound | Vision | Historic | Drugs | Glossary
Cardiovascular Terms  
Cardiovascular System Development See also Heart terms, Immune terms and Blood terms.
  • angioblast - the stem cells in blood islands generating endothelial cells which will form the walls of both arteries and veins. (More? Blood Vessel)
  • angiogenesis - the formation of new blood vessels from pre-existing vessels following from vasculogenesis in the embryo. (More? Blood Vessel)
  • anlage (German, anlage = primordium) structure or cells which will form a future more developed or differentiated adult structure.
  • blood islands - earliest sites of blood vessel and blood cell formation, seen mainly on yolk sac chorion.
  • cardinal veins - paired main systemic veins of early embryo, anterior, common, posterior.
  • cardiogenic region - region above prechordal plate in mesoderm where heart tube initially forms.
  • 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 covering the yolk sac, lining the chorionic sac and forming the connecting stalk. Contributes to placental villi development.
  • haemocytoblasts - stem cells for embryonic blood cell formation.
  • anastomose - to connect or join by a connection (anastomosis) between tubular structures.
  • 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 the maternal endometrium.
  • 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)
  • intra-aortic hematopoietic cluster - (IAHC) blood stem cells associated with the endothelial layer of aorta and large arteries.
  • maternal decidua - region of uterine endometrium where blastocyst implants. undergoes modification following implantation, decidual reaction.
  • maternal sinusoids - placental spaces around chorionic villi that are filled with maternal blood. Closest maternal/fetal exchange site.
  • Megakaryocytopoiesis - the process of bone marrow progenitor cells developMENT into mature megakaryocytes.
  • 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.
  • 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).
  • pericytes - (Rouget cells) cells located at the abluminal surface of microvessels close to endothelial cells, mainly found associated with CNS vessels and involved in vessel formation, remodeling and stabilization.
  • pharyngeal arches (=branchial arches, Gk. gill) series of cranial folds that form most structures of the head and neck. Six arches form but only 4 form any structures. Each arch has a pouch, membrane and groove.
  • placenta - (Greek, plakuos = flat cake) refers to the discoid shape of the placenta, embryonic (villous chorion)/maternal organ (decidua basalis)
  • placental veins - paired initially then only left at end of embryonic period, carry oxygenated blood to the embryo (sinus venosus).
  • 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 barrier.
  • sinus venosus - cavity into which all major embryonic paired veins supply (vitelline, placental, cardinal).
  • splanchnic mesoderm - portion of lateral plate mesoderm closest to the endoderm when coelom forms.
  • 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).
  • truncus arteriosus - an embryological heart outflow structure, that forms in early cardiac development and will later divides into the pulmonary artery and aorta. Term is also used clinically to describe the malformation where only one artery arises from the heart and forms the aorta and pulmonary artery.
  • vascular endothelial growth factor - (VEGF) A secreted protein growth factor family, which stimulates the proliferation of vasular endotheial cells and therefore blood vessel growth. VEGF's have several roles in embryonic development. The VEGF family has 7 members (VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F, and PlGF) that have a common VEGF homology domain. PIGF is the placental growth factor. They act through 3 VEGF tyrosine kinase membrane receptors (VEGFR-1 to 3) with seven immunoglobulin-like domains in the extracellular domain, a single transmembrane region, and an intracellular tyrosine kinase sequence.
  • vasculogenesis - the formation of new blood vessels from mesoderm forming the endothelium. Compared to angiogenesis that is the process of blood vessel formation from pre-existing vessels.
  • vitelline blood vessels - blood vessels associated with the yolk sac.
  • waste products - products of cellular metabolism and cellular debris, e.g.- urea, uric acid, bilirubin.
Other Terms Lists  
Terms Lists: ART | Birth | Bone | Cardiovascular | Cell Division | Endocrine | Gastrointestinal | Genital | Genetic | Head | Hearing | Heart | Immune | Integumentary | Neonatal | Neural | Oocyte | Palate | Placenta | Radiation | Renal | Respiratory | Spermatozoa | Statistics | Tooth | Ultrasound | Vision | Historic | Drugs | Glossary

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Cite this page: Hill, M.A. (2024, March 28) Embryology Cardiovascular System - Blood Vessel Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Cardiovascular_System_-_Blood_Vessel_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G