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Trophoblast

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Embryology - 6 Dec 2021  Expand to Translate
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Introduction

(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).

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 sampling^[3]uses 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

Historic Embryology: 1904 Hubrecht | 1925 Trophoblast at Implantation | 1932 Trophoblast Morphology | 1944 Trophoblast at previllous stage

Placenta Links: placenta | Lecture - Placenta | Lecture Movie | Practical - Placenta | implantation | placental villi | trophoblast | maternal decidua | uterus | endocrine placenta | placental cord | placental membranes | placenta abnormalities | ectopic pregnancy | Stage 13 | Stage 22 | placenta histology | placenta vascular | blood vessel | cord stem cells | 2013 Meeting Presentation | Placenta Terms | Category:Placenta

Historic Embryology - Placenta 1883 Embryonic Membranes | 1907 Development Atlas | 1909 | 1910 Textbook | 1917 Textbook | 1921 Textbook | 1921 Foetal Membranes |1921 human | 1921 Pig implantation | 1922 Single placental artery | 1923 Placenta Review | 1939 umbilical cord | 1943 human and monkey | 1944 chorionic villus and decidua parietalis | 1946 placenta ageing | 1960 first trimester placenta | 1960 monkey | 1972 Placental circulation | Historic Disclaimer

Extravillous trophoblasts (week 5.5)^[4]

Some Recent Findings

• TEAD4 ensures postimplantation development by promoting trophoblast self-renewal: An implication in early human pregnancy loss ^[5] "Here, we provide evidence that transcription factor TEAD4 ensures survival of postimplantation mouse and human embryos by controlling self-renewal and stemness of trophoblast progenitors within the placenta primordium. In an early postimplantation mouse embryo, TEAD4 is selectively expressed in trophoblast stem cell-like progenitor cells (TSPCs), and loss of Tead4 in postimplantation mouse TSPCs impairs their self-renewal, leading to embryonic lethality before embryonic day E9.0, a developmental stage equivalent to the first trimester of human gestation. Both TEAD4 and its cofactor, yes-associated protein 1 (YAP1), are specifically expressed in cytotrophoblast (CTB) progenitors of a first-trimester human placenta. We also show that a subset of unexplained recurrent pregnancy losses (idiopathic RPLs) is associated with impaired TEAD4 expression in CTB progenitors. Furthermore, by establishing idiopathic RPL patient-specific human trophoblast stem cells (RPL-TSCs), we show that loss of TEAD4 is associated with defective self-renewal in RPL-TSCs and rescue of TEAD4 expression restores their self-renewal ability. Unbiased genomics studies revealed that TEAD4 directly regulates expression of key cell cycle genes in both mouse and human TSCs and establishes a conserved transcriptional program. Our findings show that TEAD4, an effector of the Hippo signaling pathway, is essential for the establishment of pregnancy in a postimplantation mammalian embryo and indicate that impairment of the Hippo signaling pathway could be a molecular cause for early human pregnancy loss." uniprot | OMIM

• Dynamics of trophoblast differentiation in peri-implantation-stage human embryos ^[6] "Single-cell RNA sequencing of cells from cultured human blastocysts has enabled us to define the transcriptomic landscape of placental trophoblast (TB) that surrounds the epiblast and associated embryonic tissues during the enigmatic day 8 (D8) to D12 peri-implantation period before the villous placenta forms. We analyzed the transcriptomes of 3 early placental cell types, cytoTB (CTB), syncytioTB (STB), and migratoryTB (MTB), picked manually from cultured embryos dissociated with trypsin and were able to follow sublineages that emerged from proliferating CTB at the periphery of the conceptus. A unique form of CTB with some features of STB was detectable at D8, while mature STB was at its zenith at D10. A form of MTB with a mixed MTB/CTB phenotype arose around D10. By D12, STB generation was in decline, CTB had entered a new phase of proliferation, and mature MTB cells had begun to move from the main body of the conceptus. Notably, the MTB transcriptome at D12 indicated enrichment of transcripts associated with IFN signaling, migration, and invasion and up-regulation of HLA-C, HLA-E, and HLA-G. The STB, which is distinct from the STB of later villous STB, had a phenotype consistent with intense protein export and placental hormone production, as well as migration and invasion. The studies show that TB associated with human embryos is in rapid developmental flux during peri-implantation period when it must invade, signal robustly to the mother to ensure that the pregnancy continues, and make first contact with the maternal immune system."

• Gene expression patterns associated with human placental trophoblast differentiation ^[7] "Cell fusion is a hallmark of placental trophoblast cell differentiation and the mature syncytiotrophoblasts play essential roles for fetal-maternal exchange and production of pregnancy-related hormones. Using a well-established in vitro trophoblast differentiation model, we performed a microarray analysis on mRNA expression in trophoblast and syncytiotrophoblast cell cultures. Dramatic changes in gene expression patterns were detected during trophoblast differentiation. Real-time PCR analysis confirmed the reliability of the microarray data. As many as 3524 novel and known genes have been found to be up- or down-regulated for >2-fold. A number of cell cycle regulator including CDC6, CDC20, Cyclins B2, L1 and E2, were down-regulated in the syncytiotrophoblast, providing a mechanism for the loss of mitotic activity during trophoblast differentiation."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Trophoblast | Cytotrophoblast | Syncytiotrophoblast | Extravillous Trophoblast | syncytins

Older papers

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. See also the Discussion Page for other references listed by year and References on this current page. A comparative study of five physiological key parameters between four different human trophoblast-derived cell lines[8] "Here, we present a comparative study on the functional aspects of the choriocarcinoma cell lines BeWo, JAR and Jeg-3, as well as the first trimester trophoblast cell line ACH-3P as placental in vitro barrier models for endocrine and transport studies. Functional assays including tight junction immunostaining, sodium fluorescein retardation, trans epithelial resistance, glucose transport, hormone secretion as well as size-dependent polystyrene nanoparticle transport were performed using the four cell types to evaluate key functional parameters of each cell line to act a relevant in vitro placental barrier model." Human extravillous trophoblasts penetrate decidual veins and lymphatics before remodeling spiral arteries during early pregnancy [4] "To study the invasion of maternal endometrium between (W) 5.5 - 12 weeks of gestation by EVTs, we combined fluorescence in situ hybridization, immunofluorescence and immunohistochemistry to determine the presence of (male) EVTs in the vasculature of the maternal decidua. We observed that interstitial mononuclear EVTs directly entered decidual veins and lymphatics from W5.5. This invasion of decidual veins and lymphatics occurred long before endovascular EVTs remodelled decidual spiral arteries." The trophoblast plug during early pregnancy: a deeper insight [9] "During the first trimester of pregnancy, foetal endovascular trophoblasts invade into maternal spiral arteries, accumulate and form plugs in the lumen of the vessels. These plugs only allow blood plasma to seep through. Hence, during the first trimester of pregnancy, a first flow of fluids through the placental intervillous space is established, resulting in a physiological oxygen gradient between mother and foetus. The trophoblast plugs block spiral arteries until the beginning of the second trimester (11-14 weeks)." MSX2 Induces Trophoblast Invasion in Human Placenta [10] "Normal implantation depends on appropriate trophoblast growth and invasion. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may be associated with pre-eclampsia." OVO-like 1 regulates progenitor cell fate in human trophoblast development [11] "Epithelial barrier integrity is dependent on progenitor cells that either divide to replenish themselves or differentiate into a specialized epithelium. This paradigm exists in human placenta, where cytotrophoblast cells either propagate or undergo a unique differentiation program: fusion into an overlying syncytiotrophoblast. Syncytiotrophoblast is the primary barrier regulating the exchange of nutrients and gases between maternal and fetal blood and is the principal site for synthesizing hormones vital for human pregnancy. How trophoblast cells regulate their differentiation into a syncytium is not well understood. In this study, we show that the transcription factor OVO-like 1 (OVOL1), a homolog of Drosophila ovo, regulates the transition from progenitor to differentiated trophoblast cells. OVOL1 is expressed in human placenta and was robustly induced following stimulation of trophoblast differentiation. Disruption of OVOL1 abrogated cytotrophoblast fusion and inhibited the expression of a broad set of genes required for trophoblast cell fusion and hormonogenesis. OVOL1 was required to suppress genes that maintain cytotrophoblast cells in a progenitor state, including MYC, ID1, TP63, and ASCL2, and bound specifically to regions upstream of each of these genes." OMIM - OVOL1 Establishment of Trophoblast Stem Cells under Defined Culture Conditions in Mice [12] "Here, we report that addition of FGF2, activin A, XAV939, and Y27632 are necessary and sufficient for derivation of TS cells from both of E3.5 blastocysts and E6.5 early postimplantation extraembryonic ectoderm. Moreover, the undifferentiated TS cell state can be stably maintained in chemically defined culture conditions. Cells derived in this manner expressed TS cell marker genes, including Eomes, Elf5, Cdx2, Klf5, Cdh1, Esrrb, Sox2, and Tcfap2c; differentiated into all trophoblast subtypes (trophoblast giant cells, spongiotrophoblast, and labyrinthine trophoblast) in vitro; and exclusively contributed to trophoblast lineages in chimeric animals. This delineation of minimal requirements for derivation and self-renewal provides a defined platform for precise description and dissection of the molecular state of TS cells." Cell fusion induced by ERVWE1 or measles virus causes cellular senescence. [13] "Cellular senescence limits proliferation of potentially detrimental cells, preventing tumorigenesis and restricting tissue damage. However, the function of senescence in nonpathological conditions is unknown. We found that the human placental syncytiotrophoblast exhibited the phenotype and expressed molecular markers of cellular senescence. During embryonic development, ERVWE1-mediated cell fusion results in formation of the syncytiotrophoblast, which serves as the maternal/fetal interface at the placenta." Early Expression of Pregnancy-Specific Glycoprotein 22 (PSG22) by Trophoblast Cells Modulates Angiogenesis in Mice [14] "Mouse and human pregnancy-specific glycoproteins (PSG) are known to exert immunomodulatory functions during pregnancy by inducing maternal leukocytes to secrete anti-inflammatory cytokines that promote a tolerogenic decidual microenvironment. Many such anti-inflammatory mediators also function as pro-angiogenic factors, which, along with the reported association of -murine PSG - with the uterine vasculature, suggest that PSG may contribute to the vascular adaptations necessary for successful implantation and placental development. ...Therefore, our findings indicate that despite the independent evolution and expansion of human and rodent PSG, members in both families have conserved functions, which include their ability to induce anti-inflammatory cytokines and pro-angiogenic factors as well as to induce the formation of capillary structures by endothelial cells. In summary, our results indicate that PSG22, the most abundant PSG expressed during mouse early pregnancy, is likely a major contributor to the establishment of a successful pregnancy." Involvement of transcription factor NR2F2 in human trophoblast differentiation [15] "During the in vitro differentiation of human villous cytotrophoblast (CTB) cells to a syncytiotrophoblast (STB) phenotype, mRNA levels for the nuclear hormone receptor NR2F2 (ARP-1, COUP-TFII) increase rapidly, reaching a peak at day 1 of differentiation that is 8.8-fold greater than that in undifferentiated CTB cells." Angiogenic growth factors [16] "Fourteen angiogenic growth factors were measured by multiplex growth factor analysis or ELISA in tissue culture supernatants from EVT and CTB from pregnancies at 8-10 and 12-14 weeks' gestation. Gestational age and cell type differences were observed. Extravillous trophoblast (EVT) and villous cytotrophoblast (CTB) are major producers of angiogenic growth factors that likely contribute to placental vascular development and spiral artery remodelling."

Trophoblast and Placental Villi

Early placental development cartoon showing trophoblast contribution to placental villi.^[17]

Legend

• SYN - syncytiotrophoblasts
• sCTB - subsyncytial cytotrophoblasts (this layer grows increasingly discontinuous in later trimesters)
• EVT - extravillous cytotrophoblasts (anchor the villous tree in the decidua)

Cytotrophoblast

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.

Hyperglycosylated human Chorionic Gonadotropin (hCG) promotes the growth of cytotrophoblast cells and the endometrial invasion by these cells during implantation.^[18]

Syncytiotrophoblast

File:Cytotrophoblast to syncytiotrophoblast cartoon

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.^[19]

Human - syncytin 1 and syncytin 2

• Syncytin 2 is an envelope gene from the human endogenous retrovirus FRD (HERV-FRD)^[20]
• 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^[21]

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.

Maternal Blood - Human Chorionic Gonadotrophin (hCG) Levels

Pregnancy
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
Non-pregnant	< 5.0
Post-menopausal	< 9.5
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^[22] During the first trimester, trophoblast cells also invade both the venous and lymphatic vessels, a process shown to be compromised in recurrent spontaneous abortions.^[23]

At term, depending on maternal decidual localization, there are several identifiable subtypes:^[4]

• 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

HLA-G

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).^[24] 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.^[25] 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.^[26]

Links: HLA-G | OMIM142871

Trophoblast Infiltration

Human trophoblast invasion[27] (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. (i) The latter colonise the lumen of uterine spiral arteries and together with iCTBs, macrophages and uNK cells convert these vessels into larger conduits to guarantee adequate blood flow to the growing fetus. (ii) Various decidual cell types such as macrophages, uNK cells and decidual stromal cells interact with the interstitial cytotrophoblasts in order to control iCTB invasion in an in a spatio-temporal manner. (iii) In addition, iCTBs invade and replace the epithelium of endometrial glands. AV, anchoring villus; CC, cell column; EVT, extravillous cytotrophoblast; eCTB, endovascular cytotrophoblast; iCTB, interstitial cytotrophoblast; SA, spiral artery; ST, syncytiotrophoblast; uNK, uterine natural killer cell.

Trophoblast plugs within Spiral Arteries Week 9, GA week 11.[9] Trophoblast plugs (A) are composed of endovascular trophoblast cells. Depending on the stage of invasion and on the localization of sectioning the lumen of the spiral artery can be either completely filled with trophoblasts (1, 2) or (B) partly infiltrated (3, 4). In a plugged artery, the approaching erythrocytes are stowed by the trophoblast plug (1). Uterine glands are invaded and opened towards the intervillous space (C) by endoglandular trophoblasts. Glandular epithelial cells are replaced by endoglandular trophoblasts (5)

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.^[28] Most appear to be examples of extravillous trophoblast cells, some examples of various human "trophoblast" cell lines are listed below.

• BeWo - human choriocarcinoma^[28], hypotetraploid (modal number = 86; range = 71 to 178) (ATCC CCL-98)
• JEG-3 - choriocarcinoma HTR8/SVneo a transformed extravillous trophoblast line
• SGHPL-4 - ^{[29] [30]} 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^[31]
• ACH-3P - fusion of primary human first trimester trophoblasts (GA week 12) with a human choriocarcinoma cell line (AC1-1).^[32]
• HChEpC1b - retroviral infection by E6/E7/hTERT^[33]

Search PubMed: BeWo | JEG-3 | SGHPL-4

History

Ambrosius Arnold Willem Hubrecht (1853 – 1915)

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

August Rauber (1841-1917)

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

Abnormalities

Hydatidiform Mole

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.

Trophoblast Infections

• Malaria (More? malaria)
• Chlamydia trachomatis^[34]
• Herpesvirus 8 (HHV-8)^[35]
• Group B streptococcus (GBS)^[36]

References

1. ↑ Zhang P, Zucchelli M, Bruce S, Hambiliki F, Stavreus-Evers A, Levkov L, Skottman H, Kerkelä E, Kere J & Hovatta O. (2009). Transcriptome profiling of human pre-implantation development. PLoS ONE , 4, e7844. PMID: 19924284 DOI.
2. ↑ Tanaka N, Takeuchi T, Neri QV, Sills ES & Palermo GD. (2006). Laser-assisted blastocyst dissection and subsequent cultivation of embryonic stem cells in a serum/cell free culture system: applications and preliminary results in a murine model. J Transl Med , 4, 20. PMID: 16681851 DOI.
3. ↑ Jain CV, Kadam L, van Dijk M, Kohan-Ghadr HR, Kilburn BA, Hartman C, Mazzorana V, Visser A, Hertz M, Bolnick AD, Fritz R, Armant DR & Drewlo S. (2016). Fetal genome profiling at 5 weeks of gestation after noninvasive isolation of trophoblast cells from the endocervical canal. Sci Transl Med , 8, 363re4. PMID: 27807286 DOI.
4. ↑ ^{4.0 4.1 4.2} He N, van Iperen L, de Jong D, Szuhai K, Helmerhorst FM, van der Westerlaken LA & Chuva de Sousa Lopes SM. (2017). Human Extravillous Trophoblasts Penetrate Decidual Veins and Lymphatics before Remodeling Spiral Arteries during Early Pregnancy. PLoS ONE , 12, e0169849. PMID: 28081266 DOI.
5. ↑ Saha B, Ganguly A, Home P, Bhattacharya B, Ray S, Ghosh A, Rumi MAK, Marsh C, French VA, Gunewardena S & Paul S. (2020). TEAD4 ensures postimplantation development by promoting trophoblast self-renewal: An implication in early human pregnancy loss. Proc. Natl. Acad. Sci. U.S.A. , , . PMID: 32669432 DOI.
6. ↑ West RC, Ming H, Logsdon DM, Sun J, Rajput SK, Kile RA, Schoolcraft WB, Roberts RM, Krisher RL, Jiang Z & Yuan Y. (2019). Dynamics of trophoblast differentiation in peri-implantation-stage human embryos. Proc. Natl. Acad. Sci. U.S.A. , 116, 22635-22644. PMID: 31636193 DOI.
7. ↑ Jiang SW, Zhou W, Wang J, Little LM, Leaphart L, Jay J, Igbinigie E, Chen H & Li J. (2018). Gene expression patterns associated with human placental trophoblast differentiation. Clin. Chim. Acta , , . PMID: 29329728 DOI.
8. ↑ Rothbauer M, Patel N, Gondola H, Siwetz M, Huppertz B & Ertl P. (2017). A comparative study of five physiological key parameters between four different human trophoblast-derived cell lines. Sci Rep , 7, 5892. PMID: 28724925 DOI.
9. ↑ ^{9.0 9.1} Weiss G, Sundl M, Glasner A, Huppertz B & Moser G. (2016). The trophoblast plug during early pregnancy: a deeper insight. Histochem. Cell Biol. , 146, 749-756. PMID: 27510415 DOI.
10. ↑ Liang H, Zhang Q, Lu J, Yang G, Tian N, Wang X, Tan Y & Tan D. (2016). MSX2 Induces Trophoblast Invasion in Human Placenta. PLoS ONE , 11, e0153656. PMID: 27088357 DOI.
11. ↑ Renaud, SJ. entail., OVO-like 1 regulates progenitor cell fate in human trophoblast development PNAS
12. ↑ Ohinata Y & Tsukiyama T. (2014). Establishment of trophoblast stem cells under defined culture conditions in mice. PLoS ONE , 9, e107308. PMID: 25203285 DOI.
13. ↑ Chuprin A, Gal H, Biron-Shental T, Biran A, Amiel A, Rozenblatt S & Krizhanovsky V. (2013). Cell fusion induced by ERVWE1 or measles virus causes cellular senescence. Genes Dev. , 27, 2356-66. PMID: 24186980 DOI.
14. ↑ Blois SM, Tirado-González I, Wu J, Barrientos G, Johnson B, Warren J, Freitag N, Klapp BF, Irmak S, Ergun S & Dveskler GS. (2012). Early expression of pregnancy-specific glycoprotein 22 (PSG22) by trophoblast cells modulates angiogenesis in mice. Biol. Reprod. , 86, 191. PMID: 22423048 DOI.
15. ↑ Hubert MA, Sherritt SL, Bachurski CJ & Handwerger S. (2010). Involvement of transcription factor NR2F2 in human trophoblast differentiation. PLoS ONE , 5, e9417. PMID: 20195529 DOI.
16. ↑ Lash GE, Naruse K, Innes BA, Robson SC, Searle RF & Bulmer JN. (2010). Secretion of angiogenic growth factors by villous cytotrophoblast and extravillous trophoblast in early human pregnancy. Placenta , 31, 545-8. PMID: 20338637 DOI.
17. ↑ Robbins JR, Skrzypczynska KM, Zeldovich VB, Kapidzic M & Bakardjiev AI. (2010). Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes. PLoS Pathog. , 6, e1000732. PMID: 20107601 DOI.
18. ↑ Cole LA. (2010). Biological functions of hCG and hCG-related molecules. Reprod. Biol. Endocrinol. , 8, 102. PMID: 20735820 DOI.
19. ↑ Ruebner M, Strissel PL, Langbein M, Fahlbusch F, Wachter DL, Faschingbauer F, Beckmann MW & Strick R. (2010). Impaired cell fusion and differentiation in placentae from patients with intrauterine growth restriction correlate with reduced levels of HERV envelope genes. J. Mol. Med. , 88, 1143-56. PMID: 20664994 DOI.
20. ↑ Esnault C, Priet S, Ribet D, Vernochet C, Bruls T, Lavialle C, Weissenbach J & Heidmann T. (2008). A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2. Proc. Natl. Acad. Sci. U.S.A. , 105, 17532-7. PMID: 18988732 DOI.
21. ↑ 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.
22. ↑ Whitley GS & Cartwright JE. (2010). Cellular and molecular regulation of spiral artery remodelling: lessons from the cardiovascular field. Placenta , 31, 465-74. PMID: 20359743 DOI.
23. ↑ Windsperger K, Dekan S, Pils S, Golletz C, Kunihs V, Fiala C, Kristiansen G, Knöfler M & Pollheimer J. (2017). Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions. Hum. Reprod. , 32, 1208-1217. PMID: 28369440 DOI.
24. ↑ Yao YQ, Barlow DH & Sargent IL. (2005). Differential expression of alternatively spliced transcripts of HLA-G in human preimplantation embryos and inner cell masses. J. Immunol. , 175, 8379-85. PMID: 16339579
25. ↑ Papamitsou T, Toskas A, Papadopoulou K, Sioga A, Lakis S, Chatzistamatiou M, Economou Z & Adriopoulou L. (2014). Immunohistochemical study of immunological markers: HLAG, CD16, CD25, CD56 and CD68 in placenta tissues in recurrent pregnancy loss. Histol. Histopathol. , 29, 1047-55. PMID: 24557735 DOI.
26. ↑ Rajagopalan S, Bryceson YT, Kuppusamy SP, Geraghty DE, van der Meer A, Joosten I & Long EO. (2006). Activation of NK cells by an endocytosed receptor for soluble HLA-G. PLoS Biol. , 4, e9. PMID: 16366734 DOI.
27. ↑ Velicky P, Knöfler M & Pollheimer J. (2016). Function and control of human invasive trophoblast subtypes: Intrinsic vs. maternal control. Cell Adh Migr , 10, 154-62. PMID: 26418186 DOI.
28. ↑ ^{28.0 28.1} Pattillo RA, Gey GO, Delfs E & Mattingly RF. (1968). Human hormone production in vitro. Science , 159, 1467-9. PMID: 5753554
29. ↑ Choy MY & Manyonda IT. (1998). The phagocytic activity of human first trimester extravillous trophoblast. Hum. Reprod. , 13, 2941-9. PMID: 9804259
30. ↑ LaMarca HL, Ott CM, Höner Zu Bentrup K, Leblanc CL, Pierson DL, Nelson AB, Scandurro AB, Whitley GS, Nickerson CA & Morris CA. (2005). Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion. Placenta , 26, 709-20. PMID: 16226120 DOI.
31. ↑ Feng HC, Choy MY, Deng W, Wong HL, Lau WM, Cheung AN, Ngan HY & Tsao SW. (2005). Establishment and characterization of a human first-trimester extravillous trophoblast cell line (TEV-1). J. Soc. Gynecol. Investig. , 12, e21-32. PMID: 15866109 DOI.
32. ↑ Hiden U, Wadsack C, Prutsch N, Gauster M, Weiss U, Frank HG, Schmitz U, Fast-Hirsch C, Hengstschläger M, Pötgens A, Rüben A, Knöfler M, Haslinger P, Huppertz B, Bilban M, Kaufmann P & Desoye G. (2007). The first trimester human trophoblast cell line ACH-3P: a novel tool to study autocrine/paracrine regulatory loops of human trophoblast subpopulations--TNF-alpha stimulates MMP15 expression. BMC Dev. Biol. , 7, 137. PMID: 18093301 DOI.
33. ↑ Omi H, Okamoto A, Nikaido T, Urashima M, Kawaguchi R, Umehara N, Sugiura K, Saito M, Kiyono T & Tanaka T. (2009). Establishment of an immortalized human extravillous trophoblast cell line by retroviral infection of E6/E7/hTERT and its transcriptional profile during hypoxia and reoxygenation. Int. J. Mol. Med. , 23, 229-36. PMID: 19148547
34. ↑ de la Torre E, Mulla MJ, Yu AG, Lee SJ, Kavathas PB & Abrahams VM. (2009). Chlamydia trachomatis infection modulates trophoblast cytokine/chemokine production. J. Immunol. , 182, 3735-45. PMID: 19265152 DOI.
35. ↑ Di Stefano M, Calabrò ML, Di Gangi IM, Cantatore S, Barbierato M, Bergamo E, Kfutwah AJ, Neri M, Chieco-Bianchi L, Greco P, Gesualdo L, Ayouba A, Menu E & Fiore JR. (2008). In vitro and in vivo human herpesvirus 8 infection of placenta. PLoS ONE , 3, e4073. PMID: 19115001 DOI.
36. ↑ Kaplan A, Chung K, Kocak H, Bertolotto C, Uh A, Hobel CJ, Simmons CF, Doran K, Liu GY & Equils O. (2008). Group B streptococcus induces trophoblast death. Microb. Pathog. , 45, 231-5. PMID: 18599257 DOI.

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Leiva NL, Nolly MB, Ávila Maniero M, Losinno AD & Damiani MT. (2020). Rab Proteins: Insights into Intracellular Trafficking in Endometrium. Reprod Sci , , . PMID: 32638281 DOI.

Aplin JD. (2010). Developmental cell biology of human villous trophoblast: current research problems. Int. J. Dev. Biol. , 54, 323-9. PMID: 19876840 DOI.

Articles

Ashary N, Laheri S & Modi D. (2020). Homeobox genes in endometrium: from development to decidualization. Int. J. Dev. Biol. , 64, 237-247. PMID: 32659011 DOI.

Ralston A, Cox BJ, Nishioka N, Sasaki H, Chea E, Rugg-Gunn P, Guo G, Robson P, Draper JS & Rossant J. (2010). Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2. Development , 137, 395-403. PMID: 20081188 DOI.

Hayashi Y, Furue MK, Tanaka S, Hirose M, Wakisaka N, Danno H, Ohnuma K, Oeda S, Aihara Y, Shiota K, Ogura A, Ishiura S & Asashima M. (2010). BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin. In Vitro Cell. Dev. Biol. Anim. , 46, 416-30. PMID: 20033790 DOI.

Stoye JP. (2009). Proviral protein provides placental function. Proc. Natl. Acad. Sci. U.S.A. , 106, 11827-8. PMID: 19617545 DOI.

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.

Viswanathan SR, Mermel CH, Lu J, Lu CW, Golub TR & Daley GQ. (2009). microRNA expression during trophectoderm specification. PLoS ONE , 4, e6143. PMID: 19582159 DOI.

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Cite this page: Hill, M.A. (2021, December 6) Embryology Trophoblast. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Trophoblast

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