Pathological Placentas Research Articles

Lectin Histochemistry in the Human Placenta of Pregnancies Complicated by Intrauterine Growth Retardation Based on Absent or Reversed Diastolic Flow

The oligosaccharide distribution of the glycoconjugates was investigated in placental tissue of pregnancies complicated by intrauterine growth retardation (IUGR) with absent or reversed flow in the umbilical artery (ARED), between the 29 and the 37 weeks of pregnancy. Placentae of a gestational age-matched group of normally grown pregnancies was also selected as control group. For this purpose a battery of seven HRP-conjugated lectins was used (DBA, SBA, PNA, ConA, WGA, LTA and UEA I). Our data showed that α-D-mannose (ConA), N-acetyl-D-glucosamine (WGA), β-N-acetyl-D-galactosamine (SBA), α-L-fucose (LTA and UEA I) were present in less amount or were not present in the trophoblast and/or in the endothelial cells of the pathological group compared to the control one. The trophoblast basement membrane and/or basal plasma membrane of the pathological placentae were characterized by the presence of α-D-mannose (ConA), N-acetyl-D-glucosamine (WGA), sialic acid and D-galactose-(β1→3)-N-acetyl-D-galactosamine (neuraminidase-PNA), only in some tracts, in all the weeks of gestation. In the control placentae these sugar residues were present in the whole basement membrane and/or basal plasma membrane from 31 or 35 weeks. The Hofbauer cells of the pathological placental tissue showed a less amount or lack of α-D-mannose (ConA), β-N-acetyl-D-galactosamine (SBA) and α-L-fucose (UEA I) compared to the control ones.These results suggest that a less amount or lack of some sugar residues may contribute to restricted placenta growth and development and thus reduced efficiency in maternal-fetal exchanges of gases and metabolites.

Localization of heparanase in normal and pathological human placenta.

Degradation of extracellular matrix (ECM) components is critical for invasion. Heparan sulphate proteoglycans are abundant in the ECM of the placenta and the decidua, hence their degradation may disassemble the matrix and facilitate placentation and trophoblast invasion. This study investigates the expression of heparanase in normal and pathological placentation using RT-PCR, in-situ hybridization and immunohistochemistry analysis to detect heparanase in specific cells of the placenta and at the fetal-maternal interface throughout pregnancy. Heparanase was observed in villous cytotrophoblasts (CT), syncytial trophoblasts (ST) and in intermediate trophoblast cell columns in normal first trimester, molar and ectopic pregnancies. The heparanase protein was preferentially expressed in the endothelium of fetal capillaries, and to a much lesser extent in larger fetal vessels. Extravillous trophoblasts (EVT) invading the decidua and the maternal vessels were also heparanase positive. In the second and third trimesters, villous CT remained heparanase positive whereas ST showed variable heparanase expression. EVT invading the placental implantation site were also positively stained. A similar pattern was observed in samples obtained from pre-eclamptic placentae and from placenta accreta. Our results indicate consistent expression of heparanase in normal and abnormal placenta, in small fetal vessels and in a variety of trophoblast subpopulations with different invasive potentials.

Cloning of two novel growth hormone transcripts expressed in human placenta.

Several isoforms of human GH (hGH) are produced by two related genes expressed in the pituitary (hGH-N) and in the placenta (hGH-V). These genes consist of five exons (denoted 1-5) separated by four introns (denoted A-D). In the present report, two new transcripts of the hGH-V gene are described. The coding region of the hGH-V gene was amplified by RT-PCR using placental complementary DNA as template. DNA sequencing of several clones revealed two novel transcripts. One had a 45-bp deletion caused by the use of an alternative splice acceptor site within exon 3, similar to that in the hGH-N gene, predicting a 20-kDa isoform of hGH-V. The other transcript was generated by the use of an alternative splice donor site causing a 4-bp deletion in the end of exon 4, predicting a 24-kDa protein with 219 amino acids, which we refer to as hGH-V3. The carboxy-terminal sequence of hGH-V3 differs from 22-kDa hGH-V and hGH-V2, the two previously reported transcripts of the hGH-V gene, and does not contain a predicted transmembrane domain as described for hGH-V2. Ligase chain reaction was then used to analyze the possible use of the same splicing pattern in transcripts derived from the other genes of the hGH-gene cluster. Alternatively spliced transcripts encoding the 20-kDa hGH isoform were detected from the hGH-N and hGH-V genes, but not from the human chorionic somatomammotropin-A/B genes. The alternative splicing generating hGH-V3 was only demonstrated in transcripts derived from the hGH-V gene. Using competitive RT-PCR, the expression of hGH-V3 was estimated to be 10% of the hGH-V messenger RNA in full-term normal placentas and in placentas from pathological pregnancies. The 20-kDa hGH-V was detected in two of four full-term normal placentas, whereas a weak signal was observed in one of the pathological placentas. We conclude that the hGH-V primary transcript undergoes alternative splicing pathways generating at least four different messenger RNAs, predicting the expression of different hGH isoforms, including two with a complete sequence divergence in the carboxy-terminus.

Fas-fas ligand system-induced apoptosis in human placenta and gestational trophoblastic disease.

The low frequency of maternal immune responses to paternally inherited fetal antigens raises the following question: What regulates the immunobiology of pregnancy? Data suggest that this state is the result of peripheral immune-tolerance, an active process of immune-regulation in which activated T cells undergo apoptosis. We studied Fas ligand (FasL) expression and apoptosis in normal and pathologic placentas to find out whether the Fas-FasL-induced apoptosis takes place during implantation. FasL expression in paraffin sections was detected using specific antibodies and confirmed with reverse transcriptase-polymerase chain reaction of total RNA from frozen placentas. Apoptosis was detected using the terminal deoxy (d)-UTP nick end-labeling assay. FasL was found in the normal placenta and in gestational trophoblastic disease. Apoptotic leukocytes were localized to the maternal-fetal interface corresponding in localization with the distribution of FasL. We propose that FasL expression in the placenta is a mechanism responsible for the development of maternal immune tolerance specific for paternal alloantigens and operates in pathologic states characterized by trophoblastic invasion/proliferation.

THE PROSTACYCLIN ANALOG CARBACYCLIE, INCREASES TRANSFER IN PLACENTAE FROM PATHOLOGICAL PREGNANCIES

The vasodilator prostacyclin (PGI2) is involved in the maintenance of blood flow in the placental vascular bed. Inhibition of PGI2 synthesis reduces diffusional transfer and increases vascular pressure in the perfused human placental lobe. Reduced umbilical PGI2 synthesis is characteristic of pregnancies complicated by pre-eclampsia, IUGR or maternal smoking. We have, therefore, assessed the effect of a PGI2 analogue, carbacyclin, on antipyrine (AP) clearance in dual-perfused placental lobes from normal and pathological pregnancies. Carbacyclin (1 and 10μM), administered in the maternal afferent circulation, had no effect on AP clearance or fetal afferent perfusion pressure in normal placentae. However, in placentae from pathological pregnancies (4 pre-eclamptics, 6 smoking mothers), administration of carbacyclin (1 and 10μM) resulted in a significant increase (19%, p<0.01 and 35%, p<0.001 respectively) in AP clearance over baseline values. Increased AP clearance in placentae from smoking mothers was accompanied by a decrease in fetal afferent pressure (2-3 mm Hg). Finally, subsequent perfusion of carbacyclin-free perfusate resulted in a return of both AP clearance and fetal afferent perfusion pressure to baseline values. These results suggest that maternally-administered carbacyclin effects blood flow and nutrient transfer in the pathological human placenta and could be considered in the therapeutic approach to pathological pregnancies associated with fetal growth retardation.

Fetal microcirculation of abnormal human placenta I. Scanning electron microscopy of placental vascular casts from small for gestational age fetus

The latex injection-corrosion cast technique coupled with scanning electron microscopy was applied to the study of small for gestational age placentas. The main ultrastructural changes observed in the fetal vasculature of small for gestational age placentas were less branching of arteries and veins, capillaries with variable diameters, and many capillary bud projections; also numerous “H”-shaped anastomoses were present in the capillary network. The corrosion/cast technique approach enabled us to visualize the three-dimensional distribution of arteries, veins, and capillary network as well as the ultrastructural alterations among the various-sized vessels in the abnormal placenta. Light microscopic examination of these placentas revealed numerous syncytial knots and fibrinoid deposits pressing on arteriolar and capillary vessels at different locations. We suggest that the numerous capillary buds and anastomoses are characteristics of neovascularization and may be a compensatory phenomenon of the capillary network. This information could shed new light on alterations of physiologic functions of the pathologic placenta.

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.

Ultrasonographic findings of normal and pathologic placenta and umbilical cord

Ultrasonographic findings of normal and pathologic placenta and umbilical cord

Experimental observations on the energy metabolism of human placenta.

SummaryOxygen consumption of histologically abnormal placentae was reduced but the effect on the fetus probably depends on the timing of the abnormality. A reduced placental respiratory rate, whether accompanied by no obvious histological change, or with the “senescent” changes of postmaturity, or by damage due to rehsus isoimmunization was associated with an adverse effect on fetal growth or wellbeing.Rotenone, antimycin A and cyanide, all inhibitors of mitochondrial electron transfer, markedly decreased the endogenous respiration of both normal and pathological placentae. Respiration was also reduced by from 35 per cent to 60 per cent by oligomycin, whereas it was increased by as much as 70 per cent by 2,4‐dinitrophenol. Oligomycin inhibition of endogenous respiration was largely offset by 2,4‐dinitrophenol. The results obtained showed that: (i) placental respiration was decreased in all the pathological conditions studied, (ii) the organization of the mitochondrial respiratory chain of placental cells might be similar to that of other normal tissues and (iii) placental respiration was coupled to energy conservation reactions both in normal and pathological conditions.

ESTIMATION OF CIRCULATING RENIN IN NORMAL AND TOXEMIC PREGNANCY.

Plasma renin was estimated in forty-five women; 18 non-pregnant, 11 normal pregnant, 13 toxemic pregnant and 3 postpartum. It was found that plasma renin was within normal range in all of the non-pregnant and normal pregnant groups, and two of the post partum group. In one patient of the last group a high value was obtained, though it was by far lower than that in toxemic pregnancy. Eight of the 13 patients in the toxemic group were observed to have increased plasma renin. It is evident from this study that the renin-angiotensin system is concerned in the toxemia of pregnancy. But the question as to whether the elevated renin in toxemia originates from the kidney or from the pathological placenta is not yet solved.

Measurement of the villus surface in normal and pathologic placentas

The surface of the placental villi in 405 normal and pathologic placentas has been measured by means of a planimetric method. The surface area of a normal and mature placenta varies between 11 and 14 sq. M., with an average of 12.50 sq. M.In case of toxemia, hypermaturity, syphilis, erythroblastosis, and diabetes, the placental surface is decreased. In twin pregnancy it is increased in proportion to the combined weight of the 2 fetuses. The placental surface is also increased in cardiac failures.A significant decrease in the placental surface in cases of inexplicable fetal stress has been found, and it is believed that a kind of fetal stress is due to loss of placental efficiency.The method of measuring the placental surface, although slow and laborious, is of greatest interest in fetal physiology and is bound to be very useful in obstetrics.

Mineral components of normal and pathological human placenta, including the trace elements

Mineral components of normal and pathological human placenta, including the trace elements

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.