|Embryology - 2 Dec 2023 Expand to Translate|
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(Greek, trophe = "nutrition" and -blast, a primordial cell) In early development the blastocyst outer trophectoderm (TE) layer will generate all the extra-embryonic trophoblast cell types: cytotrophoblast, syncytiotrophoblast, trophoblastic column and extra-villous trophoblast cells. These cells have an important contribution to extra-embryonic tissues (fetal placenta and membranes) and processes of early development (adplantation, implantation and endocrine support of pregnancy).
|Human Blastocyst (day 5), trophoblast cells form the peripheral flattened epithelial layer of cells directly under the zona pellucida.||Mouse blastocyst labelled with trophoblast marker.|
In humans, week 1 blastocyst formation the outer layer of cells (adjacent to the zona pellucida) form a flat squamous epithelial layer of cells, the trophectoderm layer. Week 2 following blastocyst hatching the trophoblast layer is involved with initial adhesion to the uterine wall and subsequent implantation within the wall. During this period the trophoblast layer proliferates and differentiates into two distinct layers (syncitiotrophoblast and cytotrophoblast).
Following implantation, trophoblast cells continue to contribute to the placenta. Prenatal diagnosis by invasive chorionic villus sampling and [[ non-invasive cervical cell samplinguses mainly DNA from these cells.
|Historical - Who named the trophoblast cell?|
|From an 1905 paper on tubal implantation - "Hubrecht in 1889 published a monograph on the placentation of the hedgehog, showing that the developing ovum in this animal, after sequestration in a crypt, becomes imbedded in the sub-epithelial portion of the mucoa of the uterus by the action of the non-foetal ectodermal cells of the blastocyst. These cells Hubrecht named trophoblast because of their nutritive function, for by their agency the blastocyst “burrows” into the maternal tissues, both destroying and absorbing them."|
- Links: blastocyst | implantation | Week 2 | Week 3 | placenta | Prenatal Diagnosis | Trophoblast - Protein Expression | Ectopic Implantation Research
|Blastocyst Links: blastocyst | morula | fertilization | Week 1 | trophoblast | implantation | Human Day 3-6 Movie | Mouse Model Movie | Category:Blastocyst|
|Molecular: Hippo | Notch|
Some Recent Findings
|More recent papers|
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
|These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.
Trophoblast and Placental Villi
Early placental development cartoon showing trophoblast contribution to placental villi.
- SYN - syncytiotrophoblasts
- sCTB - subsyncytial cytotrophoblasts (this layer grows increasingly discontinuous in later trimesters)
- EVT - extravillous cytotrophoblasts (anchor the villous tree in the decidua)
The cytotrophoblast cells are the initial unfused trophoblast cells that cover the implanting blastocyst surface. In the late pregnancy placenta this cellular layer becomes squamous and discontinuous, with syncytiotrophoblast cells forming the main cellular barrier.
The syncytiotrophoblast cells form by fusion of rapidly dividing cytotrophoblast cells. These form the main cellular interface/barrier between the maternal blood-filled space and the placental villi, particularly at term.
- secrete proteolytic enzymes, enzymes break down extracellular matrix around cells
- Allow passage of blastocyst into endometrial wall, totally surround the blastocyst
- generate spaces, lacunae, that fill with maternal blood
- secrete Human Chorionic Gonadotropin (hCG), hormone, maintains decidua and Corpus Luteum, basis of pregnancy diagnostic test, present in urine is diagnostic of pregnancy
- Later in development placenta will secrete hCG
Cell–cell Fusion Activity
Two pairs of envelope genes of retroviral origin, syncytins, have fusogenic properties. Human endogenous retroviruses (HERVs) make up about 8% of the human genome. Recent study has shown that placentae from intrauterine growth restriction have impaired cell fusion and differentiation that correlates with reduced levels of HERV envelope genes.
Human - syncytin 1 and syncytin 2
- Syncytin 2 is an envelope gene from the human endogenous retrovirus FRD (HERV-FRD)
- Syncytin 2 receptor is Major Facilitator Superfamily Domain Containing 2 (MFSD2) (at chromosomal position 1p34.2)
- belongs to family of presumptive carbohydrate transporters with 10-12 membrane-spanning domains
- Syncytin 1 (-FRD) receptor is ASCT-1/-2
Mouse - syncytin A and syncytin B
- syncytin A is essential for trophoblast cell differentiation and syncytiotrophoblast morphogenesis
- Links: OMIM Syncytin-2
Human Chorionic Gonadotropin
hCG sources - produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary.
|Time (GA) weeks||Levels (mIU/mL)|
|0 - 1 weeks||0 - 50|
|1 - 2 weeks||40 - 300|
|3 - 4 weeks||500 - 6,000|
|1 - 2 months||5,000 - 200,000|
|2 - 3 months||10,000-100,000|
|second trimester||3,000 - 50,000|
|third trimester||1,000 - 50,000|
| Pregnancy test - greater than 20 mIU/mL (milli-international units per milliliter) is a positive result.|
Levels peak at 8 to 10 weeks of pregnancy, then decline and are lower for rest of pregnancy.
The extravillous trophoblast cells invade and maintain open the maternal spiral arteries emptying into the maternal lacunae During the first trimester, trophoblast cells also invade both the venous and lymphatic vessels, a process shown to be compromised in recurrent spontaneous abortions.
At term, depending on maternal decidual localization, there are several identifiable subtypes:
- interstitial mononuclear (and multinuclear) - dispersed in decidual mesenchyme
- endovascular - in spiral arteries lumen (or replacing endothelial cells)
- intramural - in spiral arteries tunica media
- "epithelial" lines - maternal decidua basalis basal plate with maternal endothelial cells in a mosaic fashion
An acronym for histocompatibility antigen, class I, G (also called: Human Leukocyte Antigen G, (HLA-6.0; HLA60, T-CELL A LOCUS, TCA) and is expressed on placental cytotrophoblast cells and other adult tissues. This distinct tissue distribution differs from the other HLA antigens (HLA-A, HLA-B, HLA-C) leading to the description as a non-classical class I antigen. May have a role in protecting the fetus from the maternal immune response. For example, expression of the HLA-G class, instead of HLA-A and HLA-B, may be a mechanism for avoiding clearance by maternal natural killer cells.
Human gene is located at 6p22.1 and there exist several protein isoforms from alternative splicing of messenger RNAs, membrane-bound isoforms (HLA-G 1-4) and soluble soluble (HLA-G 5-6). The molecule is a heterodimer consisting of both a heavy chain and a light chain (beta-2 microglobulin). The membrane-bound isoform heavy chain is anchored in the membrane and increased expression of the soluble form is related to higher implantation rates. Changes in HLA-G expression have been associated with increased miscarriage rates. Killer cell immunoglobulin-like receptor (KIR) 2DL4 (KIR2DL4) has been shown to act as a receptor for the soluble HLA-G, leading to a stimulation of resting natural killer (NK) cells.
|Human trophoblast invasion
(A) The placenta connects the fetus to the uterine wall and establishes a vascular connection between mother and child. The placenta is structured as villous tree and is in direct contact with maternal blood and, thus referred to as hemochorial. The site where the placenta comes in direct contact with the maternal decidua is called the fetal-maternal interface.
(B) During early pregnancy, vCTBs fuse to form multinucleated STs, which surround the placental villus. STs transport nutrients and gases from the maternal to the fetal circulation and represent the major endocrine unit of the placenta by secreting hormones such as chorionic gonadotropin, placental growth hormone or placental lactogen. AV form cell columns that attach to the maternal decidua and give rise to the EVT lineage. Invasive EVTs can be divided into iCTBs, which invade the decidual stroma and become terminally differentiated multinucleated GCs, or eCTBs.
|Trophoblast plugs within Spiral Arteries Week 9, GA week 11.
Trophoblast Cell Lines
A useful component of current placentation and trophoblast research are a number of trophoblast cell lines that have been derived from a number of different sources including term placenta, choriocarcinomas and transformation of primary isolated cells. BeWo cell line is the earliest human choriocarcinoma, established in 1968. Most appear to be examples of extravillous trophoblast cells, some examples of various human "trophoblast" cell lines are listed below.
- BeWo - human choriocarcinoma, hypotetraploid (modal number = 86; range = 71 to 178) (ATCC CCL-98)
- JEG-3 - choriocarcinoma HTR8/SVneo a transformed extravillous trophoblast line
- SGHPL-4 -  SV40 (pSV3neo) transformed primary cell line express cytokeratin-7, HLA class I antigen, HLA-G, BC-1, CD9, human chorionic gonadotrophin, and human placental lactogen.
- TEV-1 - (HPV16) E6/E7 infection first-trimester extravillous trophoblast cell line
- ACH-3P - fusion of primary human first trimester trophoblasts (GA week 12) with a human choriocarcinoma cell line (AC1-1).
- HChEpC1b - retroviral infection by E6/E7/hTERT
The name "Trophoblast" was used for the first time by Ambrosius Arnold Willem Hubrecht (1853 – 1915) at the meeting of the Anatomical Congress at Wiirzburg in 1888, and its earliest definition is found in the report of that meeting in Nos. 17 and 18 of the Anatomischer Anzeiger, Bd. III. "We there read, concerning a very early stage of the hedgehog (p. 510) : Die aussere Wand der Keimblase ist verdickt (drei bis vierschichtig) und besitzt wabige Lacunen. Fur diese aussere (epiblastische) Schicht sei der. Name Trophoblast gewahlt."
- Links: The Trophoblast - A Rejoinder (1904) | Ambrosius Arnold Willem Hubrecht | Hubrecht Collection | Embryologists | Embryology History
Rauber's layer is a thinned-out trophoblast membrane lying over the embryonic disk in developing carnivores and ungulates. A recent study of cattle has shown that prevention of the loss of this polar trophoblast layer leads to ectopic domains of BRACHYURY, a gastrulation marker.
The layer is named after August A. Rauber (1841-1917) a German embryologist and anatomist.
- Links: PNAS 2020
A type of placental abnormality when only the conceptus trophoblast layers proliferates and not the embryoblast, no embryo develops, this is called a "hydatidiform mole", which is due to the continuing presence of the trophoblastic layer, this abnormal conceptus can also implant in the uterus. The trophoblast cells will secrete human chorionic gonadotropin (hCG), as in a normal pregnancy, and may appear maternally and by pregnancy test to be "normal". Prenatal diagnosis by ultrasound analysis demonstrates the absence of a embryo.
There are several forms of hydatidiform mole: partial mole, complete mole and persistent gestational trophoblastic tumor. Many of these tumours arise from a haploid sperm fertilizing an egg without a female pronucleus (the alternative form, an embryo without sperm contribution, is called parthenogenesis). The tumour has a "grape-like" placental appearance without enclosed embryo formation. Following a first molar pregnancy, there is approximately a 1% risk of a second molar pregnancy.
This topic is also covered in placenta abnormalities.
- Malaria (More? malaria)
- Chlamydia trachomatis
- Herpesvirus 8 (HHV-8)
- Group B streptococcus (GBS)
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Dupressoir A, Vernochet C, Bawa O, Harper F, Pierron G, Opolon P & Heidmann T. (2009). Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene. Proc. Natl. Acad. Sci. U.S.A. , 106, 12127-32. PMID: 19564597 DOI.
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Cite this page: Hill, M.A. (2023, December 2) Embryology Trophoblast. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Trophoblast
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