Syncytial Degeneration Research Articles

Histopathological features in advanced abdominal pregnancies co-infected with SARS-CoV-2 and HIV-1 infections: A case evaluation.

ObjectivesThis study aims to provide a semi-qualitative histopathological report of the dual SARS-CoV-2 and HIV infected placentae in the third trimester of Advanced Abdominal Pregnancy (AAP).Study designFour AAP placentae in the third trimester of pregnancy (two positive for HIV-1 and two positives for SARS-CoV-2) were histologically examined.ResultsThe SARS-CoV-2+ HIV+ placentae were dysmorphic in shape compared to the flattened disc-like shape noted in the SARS-CoV-2+HIV-, SARS-CoV-2-HIV+and SARS-CoV-2-HIV- placentae. Diffused syncytial knots and syncytial degeneration were observed in all placentae. Intermittent cytotrophoblast increase, perivillous and intravillous fibrin deposition, mononuclear inflammatory cells with widespread degeneration/necrosis of the syncytiotrophoblast and microcalcification were pronounced in the SARS-CoV-2+HIV+ compared to the SARS-CoV-2+HIV- placentae. Vascular pathological changes included thrombi, ectasis, mural hypertrophy and atherotic vessels.ConclusionElevated syncytial trophoblast injury, villitis, microcalcifications and mineralisation of the syncytial basement membrane in the AAP placentae may be due to SARS-CoV-2 viral transgression instead of HIV infection alone. Vascular malperfusion is suggestive of a hypoxic insult arising from a compensatory response to meet the fetal oxygen and nutrient demands of an AAP. Placentae from HIV infected women on antiretroviral treatment were characterised by vascular malperfusion.

Quality of placental RNA: Effects of explant size and culture duration

We evaluated the impact of placental micro (≤50 mg) and macro (∼200 mg) explants, oxygen concentration and culture method on placental RNA quality after long-term culture. Our findings show that micro explants cultured at 8% oxygen have the best RNA quality and tissue structure. Macro explants were less viable after long-term culture. Macro explants and explants undergoing syncytial degeneration produced poor quality RNA and should be avoided.

A Stereological Method for Testing Whether or Not There is Random Deposition of Perivillous Fibrin-type Fibrinoid at the Villous Surface: Description and Pilot Applications to Term Placentae

We present a stereological method for testing whether or not there is random deposition of fibrin-type fibrinoid (FTF) at the villous surface of human placenta. The method requires random sampling of tissue with test lattice lines superimposed on microscopic fields at random positions and orientations. Test lines are used to generate chance intersections with specified sub-domains of the villous surface. At least three sub-domains are distinguishable: non-syncytial knots (nonSK), syncytial knots (SK) and areas of trophoblast de-epithelialization (DEP). Other sub-domains may be included to suit individual circumstances and project aims. The relative numbers of intersections with sub-domains provide the basis for an ‘expected’ distribution. Subsequently, this is compared with an ‘observed’ distribution which can be calculated from empirical estimates of the numbers of intersections with sub-domains associated with perivillous FTF (e.g. nonSK+FTF, SK+FTF and DEP+FTF). Expected and observed distributions can be compared by a chi-squared analysis. If the null hypothesis (no difference) is rejected, chi-squared values for individual sub-domains can be analysed in order to localize and interpret sites of preferential deposition. Comparisons may be drawn for individual placentae as well as a group of placentae, thereby permitting assessment of inter-placental variability. Finally, between-group comparisons may be drawn in order to test whether or not FTF deposition patterns differ in control and other pregnancies. Worked examples of the statistical procedures are provided. Preliminary results of applications to placentae from normal and complicated (hypobaric hypoxia) pregnancies are presented. They show that FTF deposition is non-random and preferentially located at sites of de-epithelialization. De-epithelialization may be a consequence of syncytial degeneration but also, at least in part, of continuous trophoblast turnover in which syncytial fragments rich in (pre-) apoptotic nuclei detach from the epithelium and are deported from the maternal intervillous space. The nascent detachment site is immediately covered by FTF prior to repair by re-epithelialization.

Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture.

We have recently shown using dansyl-L-lysine exclusion studies that the release of human chorionic gonadotrophin (HCG) in conjunction with L-lactate dehydrogenase (LDH) from first trimester villi during organ culture is symptomatic of syncytiotrophoblast degeneration. The purpose of this study was to examine chorionic villi at the ultrastructural level in order to determine events occurring during organ culture. The tissue was sampled after 0, 24, 48 and 120 h in culture and processed for electron microscopy. In addition to confirming the previously recorded syncytial degeneration, the electron micrographs showed clearly the generation of a new syncytiotrophoblast layer. The new layer, derived from differentiating cytotrophoblast cells, was largely formed by 48 h and was maintained for at least 120 h in culture. This study demonstrates a model which provides an opportunity to study the differentiation of cytotrophoblast cells whilst they retain their anatomical relationships within the villous structure.

Human chorionic gonadotrophin release and tissue viability in placental organ culture.

The use of human chorionic gonadotrophin (HCG) secretion as a measure of viability during the organ culture of human first trimester placental tissue has become a popular practice. It has been suggested that if cultured tissue is releasing large amounts of this protein hormone, there is a high level of viability. We have found, however, that the cytosolic enzyme L-lactate dehydrogenase is released into the culture supernatant in a similar daily pattern as HCG, suggesting that tissue disruption may be occurring, resulting in some of the observed hormone release. In addition, we have shown that the uptake of the fluorescent dye dansyl-L-lysine into the syncytium increases significantly from day 0 to day 4, suggesting a loss of syncytial membrane integrity. Electron micrographs show further evidence of the syncytial degeneration at the ultrastructural level, displaying extensive vacuolation and poor microvillous cover. In contrast to the degenerated state of the syncytiotrophoblast, a high level of bromodeoxyuridine incorporation is observed for cytotrophoblasts and, in particular, stromal cells up to 5 days in culture. Overall, the results suggest that the use of HCG release as a determinant of tissue viability in placental organ culture should be treated with a degree of caution.

Thinning of the placental villous membrane during maintenance in hypoxic organ culture: structural adaptation or syncytial degeneration?

This study was undertaken in order to reinvestigate claims that the human placenta is able to adapt structurally under hypoxic stress so as to facilitate materno-fetal oxygen exchange. The results confirmed that thinning of the villous membrane does occur after maintenance for 10 h in an atmosphere of 6% oxygen, and that this effect is partially reversed by maintenance for a further 10 h under normoxic conditions (21% O 2). However, throughout these experiments the values for both the arithmetic and the harmonic mean thicknesses of the villous membrane altered in an identical fashion. This indicates that the thinning observed was not the result of redistribution of the syncytiotrophoblast around the villous surface, with movement away from the sites of the fetal capillaries as previously postulated. Rather, it must have been caused by a reduction in the total mass of the syncytium, resulting from either involution and partial degeneration of its organelles, or some form of fluid-shift phenomenon. Whatever the cause, these effects were only partially reversed after further culture for 10 h in well-oxygenated conditions. Thus whilst there is an accumulating body of evidence to suggest that the placenta can adapt structurally to hypoxia in vivo, it is apparent that the in vitro organ culture system is not a suitable model with which to investigate the process.

A Correlative Review of Acetylcholine Synthesis in Relation to Histopathology of the Human Syncytiotrophoblast

Acetylcholine (ACh) is localized in the syncytiotrophoblast layer of the human placental villous tissue. An attempt was made to correlate the ACh synthesis in different pathological placentas with the histopathology of the syncytiotrophoblast available in the literature. The ACh synthesis was estimated by 'in vitro' incubation of the placental tissue. Full-term (36-38 weeks) vaginally delivered pathological placentas and hydatid moles (28 weeks) were compared with normal placentas of the same age. The results suggested that: ACh synthesis is normal in states with normal syncytiotrophoblast (e.g., healthy greater than 42 week placenta, placenta praevia, twins, and hydramnios); high ACh synthesis is correlated with hormonal and immunological changes (e.g., diabetes mellitus and Rh-incompatibility); low levels of ACh synthesis occur in states with moderate syncytial degeneration (e.g., nephrotic syndrome and essential hypertension); very poor ACh synthesis occurs when syncytial degeneration is advanced (e.g., preeclampsia, eclampsia, intra-uterine death of fetus, vesicles of hydatid mole and placental tissue infarcts); and ACh synthesis is nil in material that is completely devoid of syncytiotrophoblast (e.g., placental tissue-like material, which rarely appears in between the vesicles of hydatid moles). In essence, the degree of reduction in ACh synthesis seems to correlate with the state of the syncytiotrophoblast in various pathological conditions; and ACh synthesis is greatly reduced during syncytial degeneration. It is concluded that the capacity of the placenta to synthesize ACh reflects the state of the syncytiotrophoblast.

Variable infection of Vero cells and homologous interference after co-cultivation with HeLa cells with persistent defective infection by Edmonston measles virus

The HeLa subline K11A-HG-1 (line of HeLa cells persistently infected with Edomonston measles virus but containing little or no transmissible infectious virus) was co-cultivated with Vero cells. Focal syncytia were formed containing measles antigen and accumulations of nucleocapsid-like structures with no detectable production of transmissible infectious virus or positive hemadsorption. The infection aborted between 2 and 3 weeks after preparation of co-cultures. Upon subculture of co-cultures, occasionally complete infections (progressive syncytial degeneration, hemadsorption, and production of transmissible infectious virus) appeared. A linear dose response curve for nontransmissible infection was obtained along with evidence that measles antigen had to be present on the surface of K11A-HG-1 cells for their infectivity for Vero cells. The basis for initiation of Vero cell infection by living K11A-HG-1 cells, but not by nonviable intact K11A-HG-1 cells killed by a virus-preserving technique, nor by disrupted K11A-HG-1 cells, is, at present, a matter of speculation. However, several lines of evidence were obtained which suggested that subsequent development of delayed variable transmissible Vero cell infection occurred because of a type of viral interference, including the presence of an inhibitor in K11A-HG-1 cultures, the bulk of which was cell-associated.

Ultrastructure of the placental villi, chorion laeve, and decidua parietalis in normal and hypertensive pregnant women

The fine structure of the placental villi, chorion laeve, and decidua parietalis from normal and hypertensive pregnant women is described. Placental villi from hypertensive women revealed an increase in syncytial degeneration and fibrinoid deposition. Also noted were greater numbers of cytotrophoblast cells. On the other hand, there were no morphologic differences detected in the cellular and noncellular elements of the chorion laeve and decidua parietalis between normal and hypertensive subjects. Secretory granules were observed in both the placental villi and the chorion laeve.

Effect of hypoxia on trophoblast in organ culture: A morphologic and autoradiographic study

Villi from mature human placentas were maintained in organ culture in 26 per cent oxygen and showed little morphologic change over a period of 10 days; others, grown in 6 per cent oxygen, showed variable syncytial degeneration and a marked increase in the number of cytotrophoblastic cells. Under hypoxic conditions the incorporation of tritiated thymidine into cytotrophoblastic cells was much increased and labeling of syncytial nuclei with this compound was considerably greater than in fully oxygenated villi. It is suggested that the cytotrophoblast proliferates under conditions of hypoxia in an attempt to repair damaged syncytium and that the findings mimic those frequently seen in placentas from toxemic patients.

Perivillous fibrin deposition in the human placenta

The incidence of perivillous deposition of fibrin was studied in a series of 715 placentas. It was found that the lesion occurred more commonly in placentas from uncomplicated pregnancies than in those from cases of pre-eclamptic toxemia or hypertension. Perivillos fibrin deposition was without deleterious effect on the well-being of the fetus, and babies in whose placentas this lesion was present had an unduly low incidence of neonatal asphyxia. Perivillous fibrin deposition was unrelated to fetal arterial disease or villous syncytial degeneration. It is concluded that perivillous deposition of fibrin is the result of eddy currents in the maternal blood of the intervillous space, and that the greater the maternal flow through the placenta the more likely is it that plaques of perivillous fibrin will be formed.

Syncytial degeneration in normal and pathologic placentas

A study of the syncytium of mature placentas has been made in order to discover some constant change which might aid in the histologic diagnosis of the toxemias of pregnancy. A moderate amount of syncytial degeneration is present in all mature placentas. There is a definite increase in the severity and amount of this degeneration in the toxemias of pregnancy. The increase is slight in the mild toxemias but marked in the severe toxemias. In the cases of eclampsia it is practically universal. In nephritis syncytial degeneration is sometimes present but is secondary to the degeneration of the villi, while it is primary in cases of toxemia. The nephritic picture is often confusing and cannot be used as a differential diagnosis except in certain cases. In complete premature separation of the placenta the syncytial degeneration corresponds to the amount of toxemia present clinically and may be absent where no toxemia is present.