Trophoblast Layer Research Articles

Temporal expression and location of colony-stimulating factor 1 (CSF-1) and its receptor in the female reproductive tract are consistent with CSF-1-regulated placental development.

During pregnancy the mouse uterine epithelial synthesis of the mononuclear phagocyte growth factor designated colony-stimulating factor 1 (CSF-1) is regulated by female sex steroids. To study the role of CSF-1 in the pregnant female reproductive tract, the temporal expression and cellular sites of synthesis of CSF-1 and CSF-1 receptor (CSF-1R) mRNA were determined. CSF-1 mRNA, predominantly the 2.3-kilobase (kb) form, was first detected by in situ hybridization in uterine epithelium prior to implantation on day 3 and subsequently increased, reaching a peak at days 14-15. Its expression was restricted to the uterine epithelium at all stages of gestation and was not localized to areas of implantation. CSF-1R mRNA was first detected in maternal decidua at day 6. It was expressed in the decidua basalis during placentation, after which its expression declined. At day 7.5, trophectodermal cells also expressed CSF-1R mRNA; during placentation, it was found also in the diploid trophoblasts. The high level of CSF-1R mRNA expression by trophoblast giant cells was independent of their location around the conceptus. There was a differential distribution of CSF-1R mRNA expression in the mature placenta, with expression in the giant trophoblastic layer greater than spongiotrophoblastic layer greater than labyrinthine layer until term. Yolk sac cells also expressed low levels of CSF-1R mRNA. The coincidence of uterine CSF-1 mRNA expression and CSF-1 synthesis with both placental growth and CSF-1R mRNA expression in decidual cells and trophoblasts strongly implicates CSF-1 in the regulation of placental growth and differentiation.

Placental toxicity in rats after administration of synthetic glucocorticoids

Administration of the synthetic glucocorticoids dexamethasone and triamcinolone to pregnant rats between gestational day (GD) 16 and 20 caused dose-dependent placental lesions on GD 21 and 22 which were detected by morphological, histochemical and immunohistochemical means. Maternal blood spaces, trophoblast layer and fetal blood vessels were altered primarily in the centre of the placental labyrinth. Less severe changes were found in the junctional zone, chorionic plate and intraplacental yolk sac. On GD 21, low doses increased the amount of glycogen, while high doses induced a loss of glycogen. gamma-glutamyl transpeptidase activity was increased in the spongiotrophoblast and the labyrinthic trophoblast and dipeptidyl peptidase IV activity in fetal capillary endothelium, whereas alpha-glutamyl aminopeptidase and microsomal alanyl amino-peptidase were not affected. Additionally, in the fetal capillary endothelium an increase of immunoreactivity for the von Willebrand factor occurred. These data suggest that synthetic glucocorticoids affect placental tissues at different and rather specific levels, which may in turn disturb placental function and contribute to fetal maldevelopment.

Fetal membranes and placenta of the African green monkey (Cercopithecus aethiops).

This study examined developmental changes in fetal membranes and placenta of Cercopithecus aethiops from a Carnegie developmental stage 12 embryo to near-term fetuses. Ultrastructurally, yolk sac cells (endoderm and mesothelium) were similar to comparable stages in other primates. Endodermal cells had few apical microvilli, abundant rough-endoplasmic reticulum, electron dense mitochondria and dense bodies. In contrast, mesothelial cells were squamous with numerous microvilli, small mitochondria and a few short strands of rough endoplasmic reticulum. Amnion cells early in gestation were squamous with few microvilli, large glycogen deposits and poorly developed cytoplasmic components. Tight junctions and desmosomes held adjacent cells together. The basal surface was smooth and the basal lamina was distinct. As development proceeded the amniotic cells became cuboidal and possessed numerous microvilli. Cytoplasmic organelles were better developed and glycogen deposits increased by mid-gestation. A thick layer of microfibrils and collagen fibers was prominent below the basal lamina. Near-term, the glycogen had virtually disappeared and the amount of lipid droplets increased. Basal infoldings and podocytic processes and the extracellular matrix had increased. The smooth chorion consisted of pseudostratified columnar cells. Cells had short microvilli, numerous granules and vesicles of variable size and electron density in early gestation. With increasing age, amounts of granules and vesicles decreased, as the endoplasmic reticulum became prominent. The chorionic trophoblast was a continuous layer in mid-pregnancy and its cells had well-developed organelles and inclusions. Late in gestation, the trophoblastic layer became discontinuous and wide intercellular spaces and channels were present. In the placenta, the trophoblastic elements showed features characteristic of primate placenta.

Thromboxane and Prostacyclin Production by Different Compartments of the Human Placental Villus*

We separated the trophoblast and villous core of human placental villi to compare thromboxane (Tx) and prostacyclin production in these two compartments with eicosanoid production by intact villi. TxB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolites of TxA2 and prostacyclin, respectively, were measured in serum-free media from 48-h incubations of intact villi, villous core tissue denuded of its trophoblast layer, and trophoblast cells. In villi, the medium TxB2 concentrations increased rapidly to a peak level of 20 +/- 9 (+/- SE) (n = 11) pg/microgram protein at 48 h; 6-keto-PGF1 alpha was first detected in medium at 20 h, and it increased to 19.6 +/- 4.0 pg/micrograms protein (n = 11) by 48 h. Compared to villi, villous core tissue denuded of its surface trophoblast layer had a 7-fold greater TxB2 level (136 +/- 17 pg/micrograms protein; n = 11) by 48 h, but a comparable level of 6-keto-PGF1 alpha (22.5 +/- 3.7 pg/micrograms protein). Trophoblast cultures produced predominantly TxB2 (109 +/- 18 pg/micrograms protein; n = 11) and had the lowest 6-keto-PGF1 alpha production among the three groups (11.4 +/- 2.6 pg/micrograms protein). At 48 h, the mean TxB2/6-keto-PGF1 alpha ratio was 1.0 in medium from intact villi, 6.2 in medium from villous core tissue, and 13.3 in medium from trophoblast cells. Indomethacin inhibited production of both eicosanoids in all cultures. Our studies indicate that intact placental villi produce equal amounts of Tx and prostacyclin, the trophoblast compartment produces predominantly Tx, and the villous core compartment produces an increased amount of Tx when denuded of its trophoblast layer. These data also suggest that the trophoblast produces an inhibitor or provides a catabolic function that limits villous core Tx production.

Hydatidiform mole: an ultrastructural analysis of syncytiotrophoblast surface organization.

The scanning ultrastructural examination of a series of 31 hydatidiform mole and 12 healthy placental specimens of similar gestational age has revealed a variety of surface architectures more common in molar tissue. Characteristic paddle-shaped sprouts, ridging of the syncytial maternal oriented surface and microgibbosities are described. These structures are explicable in terms of organellar hyperplasia of cortical cytoskeletal elements found in healthy tissue. Specific morphological evidence of involvement of these elements in a condition where aberrant growth control leads to the characteristic trophoblastic hyperplasia is a further indication that cytoskeletal elements may mediate transformation. An increase in resolution obtained over previous scanning electron microscope studies has allowed the description of detailed features such as 'caveolar collars' on the maternal oriented healthy and molar trophoblast surfaces. These observations are of relevance to understanding the mechanisms of several cell physiological processes, including transepithelial transport. New observations of a reticular organization in the surface layer of molar trophoblast indicate that a syncytioskeletal layer, with organization resembling that previously described in healthy chorionic villi, is also present in molar villi.

Placental characteristics in twin transfusion syndrome

The authors describe the histological features of the placenta in a typical case of twin-to-twin transfusion, with particular attention focused on the stereologic aspects. Villi from the anemic placental portion were slightly edematous, with small and inconspicuous vessels. The stereologic characteristics of this portion were nearer values of normal placentas. The plethoric region appears as a postmature organ, with a very thin trophoblast layer and numerous vasculo-syncytial membranes. The most dramatic alterations of this region were mainly related to the foetal capillary. According to the stereologic results, the consecutive circulatory alterations would facilitate the maternal-fetal exchanges in the plethoric placental territory, thus justifying the greater development of this twin.

ラット胎盤における栄養膜のHorseradish peroxidaseの透過性

ラット胎盤における栄養膜のHorseradish peroxidaseの透過性

The dynamic structure of rabbit blastocyst coverings. II. Ultrastructural evidence for a role of the trophoblast in neozona formation.

The neozona is the innermost layer of the complex blastocyst coverings of the rabbit and is located between the mucoprotein layer and the trophoblast. As shown previously the neozona begins to replace the zona pellucida from the 4th day post coitum (d p.c.) on (Denker and Gerdes 1979). In the present study, rabbit blastocyst coverings were checked for regional differences in their composition, comparing the embryonic and the abembryonic pole of the blastocyst, at 5 and 6 d p.c. These two stages were chosen because at 5 d p.c. a complete trophoblast layer is still present at both the embryonic disc (Rauber's layer) and the extraembryonic regions (mural and abembryonic pole trophoblast), whereas at 6 d p.c. Rauber's layer has largely degenerated. Correlation of regional differences in blastocyst coverings structure with presence or absence of an intact trophoblast is taken as suggestive evidence for a role of the trophoblast in the formation or the structural modification of blastocyst coverings components. Blastocysts of both stages were fixed in glutaraldehyde with and without ruthenium red and processed for TEM. The neozona was found to be almost equally well developed in all regions at 5 d p.c. On contrast, at 6 d p.c. (Rauber's layer defective) the neozona is consistently found to be much thinner at the embryonic disc than in the extraembryonic regions where the trophoblast is still intact. This is the first report on regional differences of the structural composition of blastocyst covering within the same blastocyst.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructure of first trimester chorionic villi with regard to the prenatal diagnosis of genodermatoses.

Hopes are held out for chorion villus sampling, a technique which is gaining more and more importance for the first trimester prenatal diagnosis of chromosomal aberrations and metabolic abnormalities. A variety of inherited skin diseases can be diagnosed postnatally and prenatally (in the second trimester) by ultrastructural diagnostic markers. For evaluation of prenatal diagnosis in the first trimester, we investigated chorionic villi derived from the trophoblast layer of the early pregnancy by light microscopy and conventional electron microscopy. The ultrastructure of the cellular layers covering the villi, i.e., the inner cytotrophoblast and the outer syncytiotrophoblast, as well as that of the connective tissue of the inner extraembryonic mesoderm, are thoroughly described in relation to the ultrastructural changes in certain genodermatoses including epidermolyses and keratinization disorders. We found that chorionic villi have only a few of the characteristics differentiated in skin, and none of the structures which are relevant to the diagnosis of genodermatoses. In our view, the ultrastructural approach is not suitable for first trimester prenatal diagnosis of genodermatoses in chorionic villi.

The killing of mouse trophoblast cells by granulated metrial gland cells in vitro.

Mouse placental cell preparations have been maintained in culture, and the types of cell that attached to the culture dish were classified according to morphological criteria. However, these morphological criteria were insufficient to determine from which trophoblast layer in the placenta all of the types of cell found in the cultures originated. Some placental cell preparations were co-cultured with granulated metrial gland (GMG) cells and these cultures were studied using time-lapse video. Various responses to contacts between GMG cells and trophoblast cells were observed. These responses included the killing of trophoblast cells by GMG cells.

Permeability of the near-term rat placenta to hydrophilic solutes.

The permeability of the rat placenta at 21 days' gestation (term is 23 days) has been measured with fetuses intact in situ and by perfusion of the fetal circulation. Intact measurements were made by removal of fetuses at known time intervals after injection of radioisotopes to the anaesthetized mother and measurement of their radioactivity content. Unidirectional clearance (Kmf) was calculated and found to be in proportion to the diffusion coefficient in water (Dw) for [14C]mannitol, [14C]sucrose, [51Cr]EDTA and [3H]inulin but was relatively high for 22Na and low for [125I]albumin. The high value for 22Na is partially explained by transfer across the yolk sac placenta; cautery of the vitelline vessels significantly reduced the Kmf for 22Na but not that for [51Cr]EDTA or [125I]albumin. The low [125I]albumin value is explained on the basis of restricted diffusion of this tracer. Perfused permeability measurements were made by injection of radioisotope into the anaesthetized mother and measurement of the radioactive content of fetal perfusate samples. Although the Kmf for Na+ was significantly (P less than 0.01) reduced by 25 per cent, there was no other significant difference between results with the perfused placentae compared with those from the intact placentae. Comparison of the intact data with similar measurements in guinea pig and human confirms the similar permeability properties of the haemochorial placentae as a whole; the extra trophoblast layers in the rat make no discernible difference.

Immunohistochemical detection of human placental cytochrome P-450-associated mono-oxygenase system inducible by maternal cigarette smoking

Several xenobiotic-metabolizing mono-oxygenase activities, in conjunction with the immunohistochemical localization of the respective cytochrome P-450 forms, were investigated in placentae from smoking and non-smoking women. The antibodies used in the immunohistochemical analyses were monoclonal antibodies (MAbs) 1-7-1 and 2-66-3, prepared against the 3-methylcholanthrene-induced and phenobarbital-induced rat liver P-450 respectively. The mono-oxygenase activities were higher in placental microsomes from smokers, although no difference was observed in microsomal P-450 content. A distinct positive staining with MAb 1-7-1 was detectable in the trophoblastic layer of all placentae from smokers. In placentae from non-smokers, minimal cytoplasmic staining was observed in large villi in a few trophoblastic cells. The staining reaction was negative when MAb 2-66-3 or non-specific antibody were used. These results demonstrate that maternal cigarette smoking induces in the trophoblastic layer of the placenta a cytochrome P-450 form which is detectable immunohistochemically with the monoclonal antibody to 3-methylcholanthrene-inducible P-450 in rat liver.

Light and electron microscopic investigation of the rat placenta after cadmium administration during pregnancy.

The morphology of the rat placenta was studied after exposure to cadmium chloride during pregnancy, using optimal fixation conditions. In contrast to previous observations, no differences were observed after cadmium administration in relative volume densities of trophoblastic tissue, maternal lacunae, fetal capillaries and connective tissue, nor in trophoblastic thickness or other morphometric features. At the ultrastructural level, the amount of glycogen in trophoblast layer II was elevated in cadmium exposed rats, but other electron microscopic features (amount and localization of lipid, degenerative vesicles, thickness and general appearance of the trophoblastic and endothelial layers and thickening or multiplication of the basal lamina) were not changed. Results obtained from the present experiments do not support the suggestion that cadmium is responsible for structural changes in the placentae of human smokers.

Trophoblast development of normal primate placenta: A morphometric study

Histological and ultrastructural changes in the morphological development of placentae at various gestational ages have been descriptive and qualitative. A few studies have applied morphometric techniques to quantify the developmental changes in the trophoblast layer and stromal constituents, including fetal vessels. The data from these studies are primarily based on light microscopic observations and were derived from midterm to older placentae. However, no distinction was made between vasculosyncytial membrane and other syncytial areas. The vasculosyncytial region of the developing placenta serves as a valuable indicator of some pathological conditions; therefore, a quantitative measure of the changes in these regions during development would be beneficial. Using placentae from early gestation to term and distinguishing between vasculosyncytial areas, the trophoblast layer was measured with morphometric techniques, and observed morphological changes were correlated with gestational age.

Localization of glycogen in the placenta of diabetic rats: a light and electron microscopic study.

The ultrastructure of the placentae on day 20 of gestation was studied in rats made diabetic by streptozotocin injection on day 13 of gestation. In the placentae of control rats most of the glycogen was found in the glycogen cells, while some of it was localized to the labyrinth trophoblastic layers. In the diabetic rats a marked increase in glycogen content, together with higher numbers of glycogen cells in the junctional zone, was seen. Glycogen was also stored in other cell types of this zone, as well as in all cell types of the placental labyrinth of the diabetic animals.

Fine structural abnormalities of the placenta in diabetic rats.

In the streptozocin-induced diabetic rat, the placenta is larger and the fetus is smaller than normal. To study cellular differences that might contribute to the size and functional disparity between diabetic and control placentas, a light- and electron-microscopic analysis was performed on 14-, 18-, and 22-day (term) control and diabetic placentas. Diabetic placentas, especially later in gestation, were marked by the presence of large numbers of glycogen-distended cells in the basal zone. Within the placental labyrinth, the trophoblastic layers of the interhemal membrane were significantly thicker in the diabetic placentas on days 18 and 22, and large accumulations of liid droplets were present, especially in the inner two trophoblastic layers. In normal placentas there is a marked thinning of the placental barrier in the labyrinth by day 22 of gestation, making the thickness of the labyrinthine layers in age-matched diabetic placentas even more impressive. Finally, the labyrinth of 22-day diabetic placentas contained more glycogen and rough endoplasmic reticulum in the inner trophoblastic layer, a feature that is found in less-mature (18-day) control placentas. Thus, the diabetic placentas have a number of features that are consistent with functional immaturity/dysmaturity. Cytologic evidence confirms the presence of increased glycogen and lipid reserves in both the junctional zone and the cellular area between maternal and fetal blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrophagocytosis by the trophoblast in a bovine placentome.

A minute extravasated blood spot appeared in a space between the base of chorionic stem villi and caruncular septa as early as the 76th day of gestation, increased in number and size with the progress of gestation, and developed to the hematoma after 150 days of gestation. Epithelial layer of the caruncular septal tissue facing the arcade zone contained a large quantity of lipid droplets and showed signs of degeneration. Degenerative products are assumed to be absorbed by the trophoblast as a histotrophe. In addition, the trophoblast layer of the chorion facing the hematoma showed a distinct erythrophagocytosis of extravasated blood cells with the progress of gestation. Trophoblast cells lining an arcade zone were high columnar and showed well developed organelles suitable for strong phagocytosis. The activity of acid phosphatase was detected only in the trophoblast of the arcade zone. Processes of the ingestion and digestion of erythrocytes were almost similar to those described by earlier authors in other types of placentae. Intercellular space being developed particularly in a basal zone of the trophoblast seemed to be the important channel to transport the digested material. Erythrophagocytizing trophoblast layers often invaginated into the mesenchyme. Trophoblast cells of these invaginated layers usually contained abundant hematogenous pigment in a basal zone. These facts suggest that the intracellular digestion of erythrocytes requires a long time.

The early development of the sheep trophoblast and the involvement of cell death.

During the period of rapid elongation prior to the initiation of placental attachment (days 12-16 of gestation), the ovine blastocyst consists of a single layer (primarily) of roughly cuboidal trophoblastic cells with an inner lining of flattened endodermal cells. Well-developed spot desmosomes link the adjacent cell borders in both the trophoblastic and endodermal layers. The trophoblastic cells contain acid phosphatase-positive, lysosomelike organelles, the mean diameter of which increases greatly between days 12 and 16 and whose contents vary during development. Also during the developmental period studied, trophoblast cells accumulate lipid; and periodic acid-Schiff-positive binucleate cells appear within the trophoblast layer. A consistent observation throughout the 5 days of rapid growth and differentiation of the blastocyst was the death and disintegration of some trophoblast cells. These disintegrating cells are usually singly dispersed within the trophoblast, although occasionally groups of four or five are observed. The cell death may indicate overall remodelling of the blastocyst, or the cells may represent genetically deficient cells which are unable to respond to the appropriate signal to differentiate.

Ultrastructural observations on the chorioallantoic placenta of the golden‐rumped elephant shrew, Rhynchocyon chrysopygus

SummaryThe chorioallantoic placenta of the elephant shrew (Rhynchocyon) was studied at the ultrastructural level. The placenta is haemonochorial with an appparent lack of microvilli on the syncytiotrophoblastic surface. There is, however, an unusual development of subsurface bays which are covered only by an ectoplasmic layer of trophoblast. The contents of the bays is PAS‐negative and is similar in both texture and appearance to the maternal blood plasma. The basal trophoblastic cells are exceptionally tall and are held together by numerous desmosomes. Their basal lamina, which is on the trophospongial side, it unusually thick. At the fetomaternal junction the basal trophoblastic cells are coated with a finely granular electron‐dense precipitate of unknown nature.Electron‐dense particles resembling iron deposits are demonstrable in the fetal mesenchyme of the labyrinthine zone.

263 HISTOLOGIC ABNORMALITIES IN THE DIABETIC RAT PLACENTA

In previous work with the diabetic (DM) pregnant rat we found placentas to be larger and fetuses smaller than normal. To study cellular differences that might contribute to the disparity in size and function of DM placentas, we analyzed by light and electron microscopy DM and control placentas on days 14, 18, and 22 (term). DM was induced using IV streptozotocin (45 mg/kg).DM placentas (days 18 and 22) were marked by the presence of large numbers of glycogen-distended cells in the junctional zone. The trophoblastic layers in the interhemal membrane were also significantly thicker in the DM group, and large accumulations of lipid droplets were prominent. Since there is normally a striking thinning of the labyrinthine placental barrier by day 22, the thickness of age-matched DM placentas is more impressive, and possibly increases the diffusion distance in the DM placentas. Moreover, 22-day DM placentas contained more glycogen and rough endoplasmic reticulum in the inner trophoblastic layer, a feature similar to 18-day control placentas.Thus, DM placentas have a number of features that are normally seen earlier in gestation. Histologic evidence confirms increased glycogen and lipid in both the junctional zone and in the cellular barrier between maternal and fetal blood. We speculate that the thickening and modifications of the cellular barrier in DM may affect fetal growth and nutrition by increasing the diffusion distance between the maternal and fetal circulations.