The trophoblastic cell mass differentiates into an inner layer of cytotrophoblast, characterized by uniform cells with clear cytoplasm, distinct cell membranes, and vesicular nuclei, and an outer layer of syncytiotrophoblast, multinucleated cells with dense nuclei suspended in abundant amphophilic cytoplasm. Between the cytotrophoblast and the syncytiotrophoblast are large mononuclear cells (sometimes they may have more than one nucleus) with abundant amphophilic cytoplasm and have been designated intermediate trophoblast (X-cells or interstitial trophoblast). They emanate from the cytotrophoblast. The intermediate trophoblastic cells display a gradient of increasing size proportional to their distance from the cytotrophoblastic stem cells and fuse, particularly at the advancing margin, to form the syncytiotrophoblast.
Between the 9th and 13th post-fertilization days, blood-filled lacunae form within the rapidly growing trophoblastic mass and separate it into trabecular columns. As the lacunae enlarge, extensions of trophoblast left between them are called primary or trophoblastic stem villi. By the 15th day the different germ layers are forming in the embryo, and mesoderm has grown out from the developing embryo to form a lining for the shell of the trophoblast that surrounds the blastocyst . When the trophoblast has gained a lining of mesoderm, it is called the chorion. The mesoderm then extends into the villi to provide them with a mesodermal core; when this happens, the villi are called secondary or definitive stem villi. These grow and branch. Fetal blood vessels develop in the mesoderm in their cores, and later these vessels become connected to the fetal circulation. The villus is now known as the tertiary stem villus. Following the formation of chorionic villi, the cytotrophoblast on the villous surface appears to fuse directly into syncytiotrophoblast to form villous trophoblast. In addition, along one margin of what are to become "anchoring villi", cytotrophoblast differentiates into solid columns of intermediate trophoblastic cells. From the columns, intermediate trophoblastic cells infiltrate the decidua and myometrium to continue the formation of extra-villous trophoblast. Unlike the abrupt transition between cytotrophoblast and syncytiotrophoblast on the villous surface, there is a continuous spectrum of differentiation from cytotrophoblast through intermediate trophoblast to syncytiotrophoblast in the columns.
Human chorionic gonadotropin (hCG), human placental lactogen (hPL), and pregnancy- specific beta 1-glycoprotein (SP1) are most widely distributed in the syncytiotrophoblast. The intermediate trophoblast contains a considerable amount of both hPL and SP1 throughout pregnancy as well as small amount of hCG early in gestation. After the first trimester, there is a marked diminution of hCG in both the syncytiotrophoblast and intermediate trophoblast. In contrast, both hPL and SP1 increase during the second and third trimesters. None of these hormones is localized in the cytotrophoblast.
The decidua is all but the deepest layer of endometrium which is destined to be shed when a baby is born. The decidua that lies between the chorionic sac and the basal layer of the endometrium is called the decidua basalis. The decidua basalis becomes the maternal part of the placenta. This is the only part of the placenta of maternal origin. The endometrium that lies between the chorionic sac and the myometrium is called the basal plate (decidua basalis plus the basal layer of the endometrium). The decidua parietalis lines the entire pregnant uterus except where the placenta is forming. The decidua capsularis is the portion of endometrium superficial to the developing embryo. As the embryo becomes larger, the decidua capsularis has to cover a larger and larger area and becomes very thin and atrophic. After 3-4 month the size of the chorionic sac that contains the embryo has become so large that the decidua capsularis comes in contact with the decidua parietalis at the opposite surface of the uterus; hence the uterine cavity is obliterated. The decidua capsularis thereupon blends with the decidua parietalis and disappears as a separate layer.
Until about 12 to 16 weeks, the entire surface of the chorionic sac is covered with chorionic villi. As the sac enlarges, those villi associated with the decidua capsularis degenerate and become atrophic, so that by 16 weeks the greater part of the surface of the sac is smooth. This large area is called the chorion laeve. The remainder of the surface of the sac, that is, the part adjacent to the decidua basalis continues to be covered with villi which keep growing and branching. This part which constitute the fetal part of the placenta is called chorion frondosum. By 16 weeks the placenta is discoid in shape, consisting of chorion frondosum and associated decidua basalis. At the time of birth it occupies almost one third of the internal surface of the expanded uterus.
Septa appear in the placenta at about 3 months. These are composed of irregular folds of the basal plate that are drawn into the intervillous space by the relatively slowly growing anchoring villi. The cell islands that occur in the septa are the intermediate trophoblastic cells.
The terminal villi are the functional units of the placenta. Their appearance changes drastically over the course of normal gestation. Immature first trimester villi are large (170 micra in diameter) and are covered by two distinct layers of trophoblast, an inner layer of cytotrophoblast and an outer layer of syncytiotrophoblast. The villous stroma is very loose and mucoid in appearance. Hofbauer cells, the fetal tissue macrophages of the placenta, are numerous. Vessels are small and centrally placed.
Second trimester villi average 70 micra in diameter. The syncytiotrophoblastic layer is thinner, and the nuclei are less evenly dispersed. The cytotrophoblast does not form a continuous layer and is difficult to find after 16 weeks. The villous stroma is more compact and contains some collagen. Hofbauer cells are less conspicuous. Villous capillaries are larger and more numerous.
Mature villi are smaller still (average 40 micra in diameter). The syncytiotrophoblastic nuclei are irregularly aggregated to form syncytial knots which are found in about 30% of mature terminal villi. The stroma of the terminal villi is reduced to thin strands compressed between the numerous dilated capillaries, which constitute almost the entire surface of such villi.
The intervillous space develops rapidly to become an enormous blood sinus bounded on one side by the chorion (chorionic plate) and on the other side by the decidua basalis. It is filled with maternal blood. Fibrin deposits are also present.
The parenchyma of the umbilical cord is composed of Wharton's jelly. This material is composed of, in large part, mucopolysaccharides. It is derived from the extra- embryonic mesoblast. It contains evenly distributed spindle-shaped fibroblasts with long extensions and numerous mast cells.
Two arteries and one vein are present in the normal umbilical cord embedded in the Wharton's jelly. The arteries spiral in parallel around the vein. The arteries possess no internal elastic lamina and have a double-layered muscular wall composed of interlacing smooth muscle bundles. The umbilical vein has an elastic subintimal layer. Compared to the arteries, the vein has a larger diameter and a thinner muscular coat consisting of a single layer of circular smooth muscle. There are no vasa vasorum or lymphatic channels present in the umbilical cord. Fetuses beyond 20 weeks of gestation, however, have vasa vasorum in the intra-abdominal portions of their umbilical arteries. The umbilical vessels divide within the chorionic plate and dive beneath this layer to establish the circulation of primary vascular ramification ending in the terminal villi. In the chorionic vasculature, no distinction can be made between branches of the umbilical vein and umbilical arteries using histologic criteria. However, the gross anatomic distribution is very distinctive. Arteries always cross over veins when observed on the fetal surface of the placenta.
Remnants of the yolk sac and urachus can be found in the umbilical cord close to its fetal insertion.
The amnion is the innermost aspect of the embryonic cavity. By 12 weeks the amniotic cavity completely occupies the chorionic sac. The cavity remains filled with amniotic fluid, which by the end of gestation amount to approximately one liter. It is lined by a single layer of flat to cuboidal epithelial cells that reside on a basement membrane. The basement membrane is attached to an underlying thin layer of connective tissue. The amnion, although adjacent to the chorion, is not truly fused to it. The amnion is avascular.
The chorion forms the base for peripherally radiating villi and serves to encapsulate the early embryo and developing amnion. It is composed of a connective tissue membrane that carries the fetal vasculature. Its inner aspect is bounded by the outer layer of amnion, and its outer aspect is directly associated with the trophoblastic villi that sprout from the surface.
The functional components of the mature breast comprise the milk-producing lobular units and a system of branching ducts which connect them with the nipple-areolar complex. Surrounding these functional units are variable amount of fat and connective tissue which make up most of the bulk of the breast. Dense connective tissue extends from the underlying pectoralis fascia to the skin of the breast (Cooper's ligaments). These 'ligaments' hold the breast upward and their lengthening is presumed responsible for drooping of the breast with advanced age.
The stratified squamous epithelium of the surface extends a short distance into the openings of the major ducts. The transition from this squamous epithelium to the columnar or cuboidal epithelium which characterize the entire duct system occurs abruptly. A continuous layer of luminal epithelial cells with oval nuclei perpendicular to the surface lines the lactiferous ducts. A discontinuous layer of myoepithelial cells exists between the basement membrane and the luminal epithelial cells. The long axis of the epithelial cell is perpendicular to that of the myoepithelial cell.
The ducts are surrounded by a loose fibrous tissue with a capillary network richer than that seen in the surrounding connective tissue and fat beyond this area.
A transient mammary hyperplasia is observed in some newborn infants as a result of transplacental transfer of the maternal hormones. The hyperplastic tissue involutes by the third to fourth postpartum week.
During childhood, some branching of the primary duct system occurs but significant changes do not become apparent until puberty. The changes taking place during puberty and adolescence result from a surge of hormonal activity by the pituitary gland and ovaries. The adult breast assumes its final protuberant appearance with pigmented nipple and areola about three to four years following the initial surge of hormonal activity.
Most epithelial growth in the breast occurs before the end of the 6th month of pregnancy; further growth occur but very slowly. However, the breasts continue to enlarge; this is due chiefly to the cells of the acini beginning to secrete a fluid that begins to expand them. This secretion is called colostrum. After parturition, colostrum is secreted more abundantly but only for 2 or 3 days, after which the breast begins to secrete milk. The colostrum contains a higher concentration of protein than milk, but very little fat.
During lactation, the lobules are packed with secretory acini, among which intralobular ducts may be seen. Some acini are distended with secretion, and some contain only a little. The interlobular septa are greatly thinned.
The returning of the 'resting' stage after lactation encompasses a period of at least three months, but the degree and rate at which it occurs varies. These changes occur after discontinuing breast feedings. The breasts regain gradually the microscopic structure they had before pregnancy. However, some of the acini persist.
The areola enlarges and becomes more pigmented during pregnancy; these changes are permanent.