Cytotrophoblast

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Cytotrophoblast
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Primary chorionic villi. Diagrammatic.
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Secondary chorionic villi. Diagrammatic.
Details
Carnegie stage 5a
Days8
Identifiers
Latin cytotrophoblastus
TE E6.0.1.1.4.0.5
FMA 83039
Anatomical terminology

"Cytotrophoblast" is the name given to both the inner layer of the trophoblast (also called layer of Langhans) or the cells that live there. It is interior to the syncytiotrophoblast and external to the wall of the blastocyst in a developing embryo.

Contents

The cytotrophoblast is considered to be the trophoblastic stem cell because the layer surrounding the blastocyst remains while daughter cells differentiate and proliferate to function in multiple roles. There are two lineages that cytotrophoblastic cells may differentiate through: fusion and invasive. The fusion lineage yields syncytiotrophoblast and the invasive lineage yields interstitial cytotrophoblast cells. [1]

Cytotrophoblastic cells play an important role in the implantation of an embryo in the uterus.

Fusion lineage

The formation of all syncytiotrophoblast is from the fusion of two or more cytotrophoblasts via this fusion pathway. This pathway is important because the syncytiotrophoblast plays an important role in fetal-maternal gas exchange, nutrient exchange, and immunological and metabolic functions.

An undifferentiated cytotrophoblastic stem cell will differentiate into a villous cytotrophoblast, which is what constitutes primary chorionic villi, and will eventually coalesce into villous syncytiotrophoblast. The formation of syncytiotrophoblast from cytotrophoblast is a terminal differentiation step of trophoblastic cells. [2]

Syncytialization of cytotrophoblastic cells can be induced in vitro through multiple signalling molecules including epidermal growth factor, glucocorticoids, and human chorionic gonadotropin. [3] [4] [5]

Invasive lineage

Histopathology of a chorionic villus, in a tubal pregnancy. Histopathology of tubal pregnancy.jpg
Histopathology of a chorionic villus, in a tubal pregnancy.

The invasive lineage creates cytotrophoblasts that are essential in the process of implantation and forming a fully functional placenta. An undifferentiated cytotrophoblastic stem cell will differentiate into an extravillous cytotrophoblast intermediate and then into an interstitial cytotrophoblast. An interstitial cytotrophoblast may then further differentiate into an endovascular cytotrophoblast or form a syncytium. [2]

Interstitial cytotrophoblast

The primary function of an interstitial cytotrophoblast is to anchor the growing fetus to the maternal uterine tissue. These cells may invade the whole endometrium and the proximal third of the myometrium.

Once these cells penetrate through the first few layers of cells of the decidua, they lose their ability to proliferate and become invasive. This departure from the cell cycle seems to be due to factors such as TGF-β and decorin. Although these invasive interstitial cytotrophoblasts can no longer divide, they retain their ability to form syncytia. Multinucleated giant cells (small syncytia) are found in the placental bed and myometrium as a result of the fusion of interstitial cytotrophoblasts. [2]

Interstitial cytotrophoblasts may also transform into endovascular cytotrophoblasts.

Endovascular cytotrophoblast

The primary function of the endovascular cytotrophoblast is to penetrate maternal spiral arteries and route the blood flow through the placenta for the growing embryo to use.

They arise from interstitial cytotrophoblasts from the process of phenocopying. This changes the phenotype of these cells from epithelial to endothelial. Endovascular cytotrophoblasts, like their interstitial predecessor, are non-proliferating and invasive.

Role in implantation

Proper cytotrophoblast function is essential in the implantation of a blastocyst. After hatching, the embryonic pole of the blastocyst faces the uterine endometrium. Once they make contact the trophoblast begins to rapidly proliferate. The cytotrophoblast secretes proteolytic enzymes to break down the extracellular matrix between the endometrial cells to allow finger-like projections of trophoblast to penetrate through. Projections of cytotrophoblast and syncytiotrophoblast pull the embryo into the endometrium until it is fully covered by endometrial epithelium, save for the coagulation plug. [6]

Associated disorders

The most common associated disorder is pre-eclampsia, affecting approximately 7% of all births. [7] It is characterized by a failure of the cytotrophoblast to invade the uterus and its vasculature, specifically the spiral arteries that the endovascular cytotrophoblast should invade. The result of this is decreased blood flow to the fetus which may cause intrauterine growth restriction. Clinical symptoms of pre-eclampsia in the mother are most commonly high blood pressure, proteinuria and edema.

Conversely, if there is too much invasion of uterine tissue by the trophoblast then a hydatidiform mole or choriocarcinoma may arise.

Additional images

Related Research Articles

<span class="mw-page-title-main">Placenta</span> Organ that connects the foetus to the uterine wall

The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate maternal and fetal circulations, and is an important endocrine organ, producing hormones that regulate both maternal and fetal physiology during pregnancy. The placenta connects to the fetus via the umbilical cord, and on the opposite aspect to the maternal uterus in a species-dependent manner. In humans, a thin layer of maternal decidual (endometrial) tissue comes away with the placenta when it is expelled from the uterus following birth. Placentas are a defining characteristic of placental mammals, but are also found in marsupials and some non-mammals with varying levels of development.

<span class="mw-page-title-main">Chorion</span> Outermost fetal membrane around the embryo in amniotes

The chorion is the outermost fetal membrane around the embryo in mammals, birds and reptiles (amniotes). It develops from an outer fold on the surface of the yolk sac, which lies outside the zona pellucida, known as the vitelline membrane in other animals. In insects it is developed by the follicle cells while the egg is in the ovary.

<span class="mw-page-title-main">Blastocyst</span> Structure formed around day 5 of mammalian embryonic development

The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the embryoblast which subsequently forms the embryo, and an outer layer of trophoblast cells called the trophectoderm. This layer surrounds the inner cell mass and a fluid-filled cavity known as the blastocoel. In the late blastocyst the trophectoderm is known as the trophoblast. The trophoblast gives rise to the chorion and amnion, the two fetal membranes that surround the embryo. The placenta derives from the embryonic chorion and the underlying uterine tissue of the mother. The name "blastocyst" arises from the Greek βλαστός blastos and κύστις kystis. In other animals this is a structure consisting of an undifferentiated ball of cells and is called a blastula.

A syncytium or symplasm is a multinucleate cell which can result from multiple cell fusions of uninuclear cells, in contrast to a coenocyte, which can result from multiple nuclear divisions without accompanying cytokinesis. The muscle cell that makes up animal skeletal muscle is a classic example of a syncytium cell. The term may also refer to cells interconnected by specialized membranes with gap junctions, as seen in the heart muscle cells and certain smooth muscle cells, which are synchronized electrically in an action potential.

<span class="mw-page-title-main">Trophoblast</span> Early embryonic structure that gives rise to the placenta

The trophoblast is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the placenta. They form during the first stage of pregnancy and are the first cells to differentiate from the fertilized egg to become extraembryonic structures that do not directly contribute to the embryo. After gastrulation, the trophoblast is contiguous with the ectoderm of the embryo and is referred to as the trophectoderm. After the first differentiation, the cells in the human embryo lose their totipotency and are no longer totipotent stem cells because they cannot form a trophoblast. They are now pluripotent stem cells.

Gestational choriocarcinoma is a form of gestational trophoblastic neoplasia, which is a type of gestational trophoblastic disease (GTD), that can occur during pregnancy. It is a rare disease where the trophoblast, a layer of cells surrounding the blastocyst, undergoes abnormal developments, leading to trophoblastic tumors. The choriocarcinoma can metastasize to other organs, including the lungs, kidney, and liver. The amount and degree of choriocarcinoma spread to other parts of the body can vary greatly from person to person.

Antepartum bleeding, also known as antepartum haemorrhage (APH) or prepartum hemorrhage, is genital bleeding during pregnancy after the 28th week of pregnancy up to delivery.

<span class="mw-page-title-main">Decidua</span> Part of uterus modified in pregnancy

The decidua is the modified mucosal lining of the uterus that forms every month, in preparation for pregnancy. It is shed off each month when there is no fertilised egg to support. The decidua is under the influence of progesterone. Endometrial cells become highly characteristic. The decidua forms the maternal part of the placenta and remains for the duration of the pregnancy. After birth the decidua is shed together with the placenta.

<span class="mw-page-title-main">Syncytiotrophoblast</span> Embryonic cell of the placental surface

Syncytiotrophoblast is the epithelial covering of the highly vascular embryonic placental villi, which invades the wall of the uterus to establish nutrient circulation between the embryo and the mother. It is a multi-nucleate, terminally differentiated syncytium, extending to 13 cm.

<span class="mw-page-title-main">Placentation</span> Formation and structure of the placenta

Placentation refers to the formation, type and structure, or arrangement of the placenta. The function of placentation is to transfer nutrients, respiratory gases, and water from maternal tissue to a growing embryo, and in some instances to remove waste from the embryo. Placentation is best known in live-bearing mammals (theria), but also occurs in some fish, reptiles, amphibians, a diversity of invertebrates, and flowering plants. In vertebrates, placentas have evolved more than 100 times independently, with the majority of these instances occurring in squamate reptiles.

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<span class="mw-page-title-main">Implantation (embryology)</span> First stage of pregnancy

Implantation (nidation) is the stage in the embryonic development of mammals in which the blastocyst hatches as the embryo, adheres, and invades into the wall of the female's uterus. Implantation is the first stage of gestation, and when successful the female is considered to be pregnant. In a woman, an implanted embryo is detected by the presence of increased levels of human chorionic gonadotropin (hCG) in a pregnancy test. The implanted embryo will receive oxygen and nutrients in order to grow.

<span class="mw-page-title-main">Intervillous space</span>

In the placenta, the intervillous space is the space between chorionic villi, and contains maternal blood.

<span class="mw-page-title-main">Human embryonic development</span> Development and formation of the human embryo

Human embryonic development, or human embryogenesis, is the development and formation of the human embryo. It is characterised by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of development. In biological terms, the development of the human body entails growth from a one-celled zygote to an adult human being. Fertilization occurs when the sperm cell successfully enters and fuses with an egg cell (ovum). The genetic material of the sperm and egg then combine to form the single cell zygote and the germinal stage of development commences. Embryonic development in the human, covers the first eight weeks of development; at the beginning of the ninth week the embryo is termed a fetus. Human embryology is the study of this development during the first eight weeks after fertilization. The normal period of gestation (pregnancy) is about nine months or 40 weeks.

<span class="mw-page-title-main">Syncytin-1</span>

Syncytin-1 also known as enverin is a protein found in humans and other primates that is encoded by the ERVW-1 gene. Syncytin-1 is a cell-cell fusion protein whose function is best characterized in placental development. The placenta in turn aids in embryo attachment to the uterus and establishment of a nutrient supply.

<span class="mw-page-title-main">Intermediate trophoblast</span>

Intermediate trophoblast is a distinct subtype of trophoblastic tissue that arises from the cytotrophoblast.

Hormonal regulation occurs at every stage of development. A milieu of hormones simultaneously affects development of the fetus during embryogenesis and the mother, including human chorionic gonadotropin (hCG) and progesterone (P4).

<span class="mw-page-title-main">Villitis of unknown etiology</span> Medical condition

Villitis of unknown etiology (VUE), also known as chronic villitis, is a placental injury. VUE is an inflammatory condition involving the chorionic villi. VUE is a recurrent condition and can be associated with intrauterine growth restriction (IUGR). IUGR involves the poor growth of the foetus, stillbirth, miscarriage, and premature delivery. VUE recurs in about 1/3 of subsequent pregnancies.

Embryotroph is the embryonic nourishment in placental mammals.

Extravillous trophoblasts(EVTs), are one form of differentiated trophoblast cells of the placenta. They are invasive mesenchymal cells which function to establish critical tissue connection in the developing placental-uterine interface. EVTs derive from progenitor cytotrophoblasts (CYTs), as does the other main trophoblast subtype, syncytiotrophoblast (SYN). They are sometimes called intermediate trophoblast.

References

  1. Handwerger, S (8 July 2010). "New insights into the regulation of human cytotrophoblast cell differentiation". Molecular and Cellular Endocrinology. 323 (1): 94–104. doi:10.1016/j.mce.2009.12.015. PMC   2874088 . PMID   20036312.
  2. 1 2 3 Bischof, P; Irminger-Finger, I (January 2005). "The human cytotrophoblastic cell, a mononuclear chameleon". The International Journal of Biochemistry & Cell Biology. 37 (1): 1–16. doi:10.1016/j.biocel.2004.05.014. PMID   15381142.
  3. Dakour, J., Li, H., Chen, H., & Morrish, D. W. (1999). "EGF promotes development of a differentiated trophoblast phenotype having c-myc and junB proto-oncogene activation." Placenta, 20, 119–126.
  4. Cronier, L., Alsat, E., Hervé, J. C., Delèze, J., & Malassiné, A. (1998). "Dexamethasone stimulates gap junctional communication, peptide hormone production and differentiation of human term trophoblast." Trophobl. Res., 11, 35–49.
  5. Yang, M., Lei, Z. M., & Rao, Ch. V. (2003). "The central role of human chorionic gonadotropin in the formation of human placental syncytium." Endocrinology, 144, 1108–1120.
  6. Schoenwolf, G.C. (2009). Larsen's Human Embryology (pp. 53, 4th Ed.). Philadelphia, PA: Churchill Livingstone.
  7. Genbacev, O., DiFederico, E., McMaster, M., & Fisher, S. (1999). "Invasive cytotrophoblast apoptosis in pre-eclampsia." Human Reproduction, 14, 59-66.