Trophoblast

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Human Blastocyst (day 5), trophoblast cells form the peripheral flattened epithelial layer of cells directly under the zona pellucida.

Introduction

(Greek, trophe = "nutrition" and -blast, a primordial cell) During early development the trophoblast cells have an important contribution to extraembryonic 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 trophoblast 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 differentiates into two distinct layers (syncitiotrophoblast and cytotrophoblast).

Links: Blastocyst | Implantation | Week 2 | Week 3 | Placenta Development

Some Recent Findings

Early Expression of Pregnancy-Specific Glycoprotein 22 (PSG22) by Trophoblast Cells Modulates Angiogenesis in Mice "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 "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 "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 remodeling."

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 <pubmed limit=5>Trophoblast</pubmed>

Trophoblast and Placental Villi

Early placental development cartoon showing trophoblast contribution to placental villi.

Legend

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

Cytotrophoblasts

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

Extravillous Cytotrophoblasts

Maintain open maternal spiral arteries emptying into the maternal lacunae

Syncytiotrophoblasts

File:Cytotrophoblast to syncytiotrophoblast cartoon

• form by fusion of rapidly dividing cytotrophoblast cells
• 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.

• levels peak at 8 to 10 weeks of pregnancy, then decline and are lower for rest of pregnancy

0-1 week: 0-50 mIU/ml 


1-2 weeks: 40-300 mIU/ml

3-4 weeks: 500-6,000 mIU/ml

1-2 months: 5,000-200,000 mIU/ml

2-3 months: 10,000-100,000 mIU/ml

2nd trimester: 3,000-50,000 mIU/ml

3rd trimester: 1,000-50,000 mIU/ml

Non-pregnant females: <5.0 mIU/ml Postmenopausal females: <9.5 mIU/ml

Abnormalities

Hydatidiform Mole

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? Abnormal Development - Malaria)
• Chlamydia trachomatis
• Herpesvirus 8 (HHV-8)
• Group B streptococcus (GBS)

References

Reviews

<pubmed>19876840</pubmed>

Articles

<pubmed>20081188</pubmed> <pubmed>20033790</pubmed> <pubmed>19617545</pubmed> <pubmed>19564597</pubmed> <pubmed>19582159</pubmed>

Search PubMed

Search October 2010

• Syncytiotrophoblast - All (10230) Review (1104) Free Full Text (2508)
• Cytotrophoblast - All (9828) Review (1062) Free Full Text (2401)

Search Pubmed: Trophoblast | syncytiotrophoblast | cytotrophoblast |

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Cite this page: Hill, M.A. (2024, May 6) Embryology Trophoblast. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Trophoblast

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