Nivel nacional

Syncytiotrophoblast Cytotrophoblast Extra embryonic mesoblast Maternal endometrium; will become the Decidua Basalis Polar/Embryonic Cytotrophoblast and Syncytiotrophoblast Embryo 1 w / Maternal endometrial epithelium Maternal endometrium; will become the Decidua

Capsularis M ural/Abembryonic Cytotrophoblast and Syncytiotrophoblast Maternal endometrium; will become the Decidual Parietalis Uterine Cavity

1.4. The uterus

The lining of the uterus can be divided into three layers from interior to exterior: the perimetrium (peritoneal covering), the myometrium (muscular coat) and the

endometrium (mucosa). If pregnancy does not occur and there is no blastocyst

implantation, the endometrium is shed at the end of the menstrual cycle. If implantation does occur the endometrium remains intact and undergoes cellular changes known as decidualisation. This is caused by the release of progesterone from the corpus luteum during implantation, and the altered endothelium becomes known as decidua. The endometrial surface consists of a simple columnar ciliated epithelium that is continuous. Its stroma is a highly cellular connective tissue with an amorphous extracellular matrix containing relatively few connective tissue fibres. During decidualisation the endometrial stromal cells enlarge, accumulate glycogen and become epithelioid in appearance on cross section (Tabanelli et al., 1992). As blastomere development ensues, the decidua becomes arranged at three topographical sites; the decidua basalis, situated at the deepest pole of the conceptus; the decidua parietalis lines the uterine cavity except at the site of implantation; the decidua capsularis is reflected over the rest of the chorionic sac (Fig 1.3).

1.5. The Placenta

During pregnancy, maternally derived mesenchyme first appears from days 7-12 post-conception. The first indication of this is the production of extra-embryonic

mesoblast from a caudally situated area of proliferation. The combination of embryonic derived trophoblast and extra-embryonic mesoblast is know as the placenta. Although venerated by the early Egyptians, the placenta was first defined as the organ responsible for fetal nutrition by the Greek physician Diogenes of Apollonia (480 B.C.) (DeWitt., 1958). The term placenta derives from the Latin for flat 'cake' and was first used by Realdus Columbus (1516-1559). Aristotle (384-322 EC) first realised that the fetus is fully enclosed by membranes which he termed chorion. During early pregnancy

trophoblast is the most abundant tissue of fetal origin. Trophoblast development depends on imprinted genes that are expressed from only the paternally derived allele (Mochizuki et al., 1996; Franklin et al., 1996). The initial day 5 single layer of cytotrophoblast differentiate into syncytiotrophoblast, villous trophoblast or extravillous (intermediate) trophoblast.

1.5.1. Chorionic villi

From day 6 post-conception, groups of cytotrophoblast cells begin to aggregate just below the layer of syncytiotrophoblast. These clumps begin to project into the

syncytiotrophoblast and are termed primary villi. These villi begin to acquire cores of mesoblasts (mesoblastic crests) and are termed secondary villi. Approximately 2 weeks post-conception the mesenchymal core then becomes vascularised resulting in tertiary (or chorionic) villi, consisting of the vascularised mesenchymal core covered by

cytotrophoblast and syncytiotrophoblast. The first chorionic villi are not free processes but villous stems, and are covered by two layers of trophoblast; the inner layer of cytotrophoblast, the so called 'Langhans' cells', and an outer layer of syncytiotrophoblast. Although both layers persist to maturity, the inner layer becomes discontinuous with advancing gestation. New production of syncytium from the Langhans layer continues throughout pregnancy, although it slows down in later gestation. Villi branch extensively and are vascularised, but contain no blood vessels in their mesoblastic core before 19 days post-conception when the first fetal capillaries are observed (a complete

fetoplacental circulation is established around the beginning of the fifth week of gestation). They entirely surround the implanted blastomere, stemming from both the polar and mural regions, and begin to form villous trees.

The development of a villous tree starts by the formation of side branches on the trabeculae. The earliest of these are composed of syncytiotrophoblast alone and so are termed syncytial sprouts. The syncytium represents one large, continuous sheet of cytoplasm in which the nuclei freely float. Frequently the nuclei bunch up irregularly, producing 'knots' or 'buds'. In early gestation these are seen arising in an apparently random pattern from the surfaces of mesenchymal and immature intermediate villi, and at all stages of gestation a proportion of these sprouts break away (Castellucci et al., 1989). Mesenchymal invasion into the proximal end of the non-shed true sprout is soon followed by the formation of capillaries, so rendering conversion into a tertiary villus complete. Up until the fifth week post-conception, mesenchymal villi formed in this way progress to become primitive stem villi. However, after this point some mesenchymal villi

differentiate into immature intermediate villi (Castellucci et al., 1989) The latter continue to produce many new syncytial sprouts until they themselves are transformed into stem villi. Hence, growth of the more structural elements of the villous tree is very rapid in the first trimester. Full villous trees consist of stem villi, mature intermediate villi, terminal

villi, immature intermediate villi and mesenchymal villi (Fig 1.4), Up until the eighth week of gestation these trees cover the entire chorion (Fig 1.3).

Early in the embryonic period, some chorionic villi develop dense masses of trophoblastic cells at their tips. These 'cytotrophoblastic cell columns' make contact with the eroded endometrium and spread out as part of the lining of the intervillous space. In the basal region they form the cytotrophoblastic shell or early basal plate. Later the villous cores extend through the cell columns to become anchored to the decidua (anchoring villi). Anchoring villi are in direct contact with the decidua. Most villi, however, retain free tips in the intervillous space; floating villi.

1.5.2. Cell columns and cell islands

Cell columns are the trophoblast connections of larger anchoring villi to the basal plate. These are segments of the villous trees that persist in the primary villus stage, because mesenchymal invasion during formation of secondary villi does not reach the most basal segments of the anchoring villi. Because of continuous cytotrophoblast proliferation at the stromal-trophoblastic interface the cell columns serve as segments of longitudinal growth of the anchoring villi. From their distal ends, cytotrophoblasts may invade the basal plate, thus contributing to the gro^vth of the latter. Because of this, cell columns serve as one of the richest sources for the so-called extravillous cytotrophoblast. Fibrinoid deposition at the surface of the cell columns slowly buries them into the basal plate. As soon as they are completely incorporated into the plate, the cytotrophoblastic proliferation slows down. After partial degeneration of the cells and complete

disintegration of their structure, cell columns largely disappear in the course of the last trimester and can only rarely be observed in term placenta.

Cell islands are largely comparable structures. They too are formed from villous tips that have not been opened up by connective tissue during the transition from primary to tertiary villi. The only difference is that these villous tips are not connected to the basal plate, as are anchoring villi. Also, the cytotrophoblast of the cell islands proliferates and later becomes largely transformed into fibrinoid, which surround clusters and strings of surviving extravillous cytotrophoblast. Sometimes central degeneration and liquefaction causes the development of fluid-filled cysts inside the cell islands. Cell biology studies concerning the proliferative behaviour of villous cytotrophoblast, the expression of growth factor receptors and of oncogene protein products, and the interactions with extracellular matrix have not revealed any differences between cell islands and cell

Figure 1.3

Human embryo at 7 weeks o f gestation