Intrauterine growth retardation: morphometry of the microvillous membrane of the human placenta

The syncytiotrophoblast microvillous membrane of the human placenta has been investigated with quantitative analyses in cases of severe fetal growth retardation associated with a marked reduction in the surface area of exchange at the peripheral villous level. This study has shown that, in placentae of intrauterine growth-retarded infants of unknown origin, there were morphological changes in the microvillous membrane characterized by an increase in the microvillous surface density and surface enlargement factor, associated with a reduction of the intermicrovillous space. It is not possible to state whether these morphological changes represent a delayed maturation of the placental tissue, or compensatory mechanisms to improve the functional efficiency of the placenta. In pre-eclampsia, these placental changes were much less pronounced, possibly due to severe uteroplacental ischaemia in this complication of pregnancy. Despite these morphological changes, both groups of placentae showed significant reductions in absolute values for the microvillous and total trophoblastic surface areas, which can have major implications on the functional efficiency of the placenta.     

胎儿生长迟缓孕妇胎盘微绒毛的体视学研究

对１２例胎儿生长迟缓及１０例正常胎儿（对照组）的盘组织进行光镜水平和电镜水平的定量观测。ＩＵＧＲ组中，胎盘正常重量指数的有６例，低重量的指数的有６例。结果：ＩＵＧＲ组胎盘重量、胎盘容积、绒毛表面积及绒毛毛细血管表面积均小于对照组，ＮＰＩ组胎盘重量、胎盘容积、绒毛表面积、绒毛毛细血管表面积、微绒行间腔表面积密度和微绒毛表面积绝驿值小于对照组及ＬＰＩ组。     

Histomorphometry of the human placenta in Class C diabetes mellitus

Placentae from Class C diabetic mothers were compared by histomorphometric analyses with a group of normal placentae. The placentae of the diabetics were divided in two groups based on the growth characteristics and neonatal outcome of the infants at birth. This study has demonstrated that the placentae of both groups were somewhat heavier than the controls due to a parallel increase in parenchymal and non-parenchymal tissues. The placentae were also shown to be characterized by a relative increase in the surface areas of exchange between mother and fetus, in terms of peripheral villous and capillary surface areas and intervillous space volume. Consequently, the results of this study suggest that, in Class C diabetics, placental morphology and placental function are probably not more adversely affected than in other less severe forms of the disease during pregnancy. Furthermore, the findings in this investigation support the hypothesis that the placental changes, and the perinatal morbidity associated with this condition, are probably the results of hormonal and metabolic abnormalities present in the mother and the fetus.     

Morphometric evaluation of the microvillous surface enlargement factor in the human placenta from mid-gestation to term

The factor by which the villous surface area is enlarged owing to the presence of microvilli has been evaluated with quantitative analyses in human placental tissues from mid-gestation to term. It has shown that, between 25 and 36 weeks of gestation, the peripheral villous surface area is enlarged by a constant factor of approximately 9.47 +/- 0.28 (mean +/- s.d.). Then, from 36 weeks to term, it has shown a significant decrease in the microvillous surface enlargement factor (9.44 to 7.67; P less than 0.01). Consequently, the actual surface area of exchange between mother and fetus was shown to be significantly decreased during that same period (93.91 to 67.02 m2; P less than 0.01). On a functional basis, these findings support the theory that, during that last four weeks of pregnancy, the increasing physiological needs of the fetus are probably met by profound functional changes in the permeability and transfer functions of the cells that constitute the placental barrier.     

Raised maternal serum alpha-fetoprotein in the absence of fetal abnormality--placental findings. A quantitative morphometric study

Ten placentae from pregnancies proceeding to term from mothers who on routine screening at 16-18 weeks gestation were found to have raised serum AFP but no increase in amniotic fluid AFP and no fetal abnormality, were studied using morphometric techniques. The results were compared with 20 placentae from normal term pregnancies where the maternal serum AFP level was not elevated. The mean total placental volume, volume of parenchyma and villous surface area were increased in the placentae associated with a raised maternal serum AFP. More of these placentae were infarcted and the fetal-placental weight ratio was significantly lower. The hypothesis that elevation of maternal serum AFP level is related to the increase in placental size is addressed.     

Placental changes in relation to the degree of metabolic control in diabetes mellitus

Placentae from 17 insulin-dependent diabetic mothers were studied in the fresh state by direct light microscopy. Twenty placentae from non-diabetic women served as controls. Cases with pre-eclampsia or other complicating diseases were excluded. Specimens from the placentae were obtained from a functionally and anatomically well-defined area. Syncytial knots, vasculosyncytial membranes, hypovascular villi, intravillous haemorrhage, subsyncytial oedema and the frequency of immature villi were tested for correlation with the degree of metabolic control of the diabetic mothers. The degree of metabolic control was expressed as MODD, mean of daily differences in matched blood glucose levels. Increasing numbers of vasculosyncytial membranes and syncytial knots were noted with increasing variability in blood glucose levels. This correlation was seen only when blood glucose values from the 12th to the 32nd week were used for calculation of MODD. MODD calculated during the 33rd week to term showed no correlation to placental changes. A higher frequency of hypovascular villi and immature villi was noted in the diabetic group, but no correlation with the degree of metabolic control was seen. Possibly both syncytial knots and vasculosyncytial membranes äre structural changes that can increase the fetomaternal exchange. The fact that placental changes correlated to the degree of metabolic control only in early pregnancy indicates the importance of early surveillance of pregnancy.     

Morphometric studies of the placentas of hypertrophic newborn infants

In a total of 31 placentae from new-born children weighing between 4000 g and 4499 g at birth and in 64 placentae from new-born children with standard weight, the relative surface of the villous vessels and the relative volumes of the villous epithelium, of the stroma and of the villous vessels are determined by the morphometric method. These morphometric parameters, which are characterising the villous vascularization and the relative placental area of exchange, are slightly greater for the placentae from overweight children compared to the values of the control group. The oral glucose tolerance test performed on the 3rd puerperal day appears to be normal in all 31 test persons. 20 mothers are overweight and their average height is about 173 cm. The results of the present study are related to the corresponding literature.     

妊娠期糖尿病胎盘微绒毛形态计量学改变与围产儿并发症关系的探讨

目的:探讨妊娠期糖尿病胎盘绒毛变化与围产儿并发症的关系。方法:选择足月妊娠期糖尿病38例的胎盘为观察组,选择正常足月妊娠30例的胎盘为对照组,分娩时在胎盘母面取材,制成快速脱水、表面喷金镀膜标本,在扫描电镜下用VIDAS型图像分析仪对胎盘微绒毛进行组织形态计量学测定。称取胎盘重量、计算胎盘系数(胎盘重量与新生儿出生体重比值),记录新生儿Apgar评分、体重、脐血胆红素及新生儿出生后30min内血糖值。结果:糖尿病孕妇的胎盘合体滋养层细胞微绒毛面积、周长、长轴、短轴小于对照组,差异均有统计学意义(P<0.05);异形指数大于对照组,差异有统计学意义(P<0.05)。扫描电镜下观察组胎盘组织超微结构病理变化明显,表现为胎盘绒毛成熟不良、水肿,合体滋养层表面微绒毛排列紊乱,直径大小不一,局部缺损,呈葡萄状。观察组胎盘重量明显高于对照组,两组差异显著(P<0.05)。胎盘系数两组间差异非常显著(P<0,01);两组新生儿窒息、出生30min内血糖值、血胆红素均有显著差异(P<0.01)。结论:妊娠期糖尿病胎盘病理变化进一步加重了胎儿缺氧,增加了新生儿窒息率,导致新生儿发生更多的并发症。     

Placental GPI-PLD is of maternal origin and its GPI substrate is absent from placentae of pregnancies associated with pre-eclampsia

Pre-eclampsia (PE) is a disorder affecting 5-10% of all pregnancies and is characterised by abnormal trophoblast invasion, maternal endothelial cell dysfunction and a systemic maternal response. A unifying factor responsible for eliciting these effects remains unknown. However, levels of the autocrine insulin mediators, inositolphosphoglycans (IPG), are elevated 3-fold in pre-eclamptic placentae compared with controls and are also elevated 3-fold in maternal urine of pre-eclamptic women, suggesting an abnormal paracrine role of the mediator in the systemic maternal response. At the placental level, IPGs are metabolic second messengers capable of eliciting some of the characteristic features of PE, such as the 10-fold increase in glycogen synthesis and 16-fold increase in the activity of the IPG-dependent enzyme glycogen synthase. IPGs are derived from their lipidic precursors, the glycosylphosphatidylinositols (GPI), in membrane associated caveolae by the action of a GPI-specific phospholipase D whose activity is regulated by its membrane microenvironment. We show that the lipidic GPI precursor was detected in total placental membrane and microvillous membrane from normal placentae. The presence of GPI could not be detected in PE placentae, suggesting that the GPI/IPG signalling system is dysregulated in this disorder. Equivalent amounts of a proteolytically-cleaved 50 kDa GPI-PLD protein is detected in both normal and PE placentae. However, GPI-PLD mRNA is absent, suggesting a mechanism of uptake from maternal serum. Since GPI-PLD, whose presence is required for hydrolysis of GPI and release of free IPG, is detectable with equal activity in both normal and PE placentae, we postulate that dysregulation of the tubular caveolar structure of the microvilli in pre-eclamptic placentae provides an environment which promotes the unregulated hydrolysis of GPI in this disorder.     

Human placental syncytiotrophoblast microvillous membranes impair maternal vascular endothelial function

Objective To investigate the hypothesis that, should there be an increase in deported syncytiotrophoblast microvillous membrane fragments in pre-eclampsia, it may cause maternal vascular endothelial dysfunction.
Design Syncytiotrophoblast microvillous membrane (STEM) vesicles, prepared from normal term placentae, were perfused through small subcutaneous arteries isolated from fat biopsies obtained at caesarean section. Endothelial function of these arteries was studied by determining acetylcholine-induced relaxation after preconstriction with noradrenaline. As controls, physiological buffer or red blood cell membranes in physiological buffer were used and endothelial function similarly estimated. Transmission electron microscopy was performed on arteries after perfusion.
Sample STBM vesicles, isolated from the placentae of three healthy women undergoing elective caesarean section for reasons unrelated to pre-eclampsia, were suspended in physiological buffer. Subcutaneous fat arteries were obtained from a separate group of 13 normotensive pregnant women, also undergoing elective caesarean section at term.
Results Perfusion with red blood cell membranes or physiological buffer had no significant effect on the concentration dependent relaxation in arteries preconstricted with noradrenaline. However, after 2 h perfusion with STBM vesicles, arteries showed a significant reduction in relaxation to acetylcholine, indicative of altered endothelial function. Transmission electron microscopy of arteries perfused with STBM vesicles confirmed endothelial disruption.
Conclusions STBM vesicle perfusion specifically altered the relaxation response of preconstricted maternal subcutaneous fat arteries to acetylcholine, suggesting an alteration in endothelial dependent relaxation. Deported microvilli may therefore be capable of producing endothelial cell damage and endothelial dysfunction observed in the maternal syndrome of pre-eclampsia.     

Molecular charge effects on the protein permeability of the guinea-pig placenta

The effect of molecular charge on protein permeability of the dually perfused guinea-pig placenta has been investigated by measurement of the permeability surface area products (PS) and observation of the ultrastructural localization of cationic horseradish peroxidase (cHRP) and anionic horseradish peroxidase (aHRP) molecules. Steady-state PS calculated from the experimental data was 0.032 +/- 0.0045 and 0.0045 +/- 0.0008 ml min-1 (mean +/- s.e.m.) for cHRP and aHRP respectively (P less than 0.01). The PS for a diffusional marker, 51Cr-ethylenediaminetetraacetic acid, showed no significant difference between the two groups. Ultrastructurally, placentae perfused with cHRP showed fewer microvilli and a dilated interstitial space compared with placentae perfused with aHRP; large vacuoles were also found in the syncytiotrophoblast in the former but not in the latter tissue. Reaction product in placentae perfused with cHRP was localized to the maternal-facing plasma membrane of the syncytiotrophoblast, in vacuoles and vesicles of the syncytiotrophoblast, and also in the basement membrane of the interstitial space, whereas placentae perfused with aHRP only had reaction product in vesicles in the syncytiotrophoblast. These results suggest that anionic sites in the guinea-pig placenta affect its permeability to charged proteins, cationic molecules inducing structural changes associated with increased permeability.     

Scanning electron microscopy of human placental villi from early and late in gestation.

Human placental villi from term placentas and from 10 to 14 week placentas were examined in the scanning electron microscope (SEM) after critical point drying. When prepared by this method, the syncytial surface appears covered with slender microvilli similar to those seen in transmission electron micrographs. We find no support in our observations for the suggestion that the trophoblastic surface is a mosaic of microvillous and nonmicrovillous areas or that substantial areas lack microvilli. In addition, the villi often show circumferentially oriented furrows. SEM's of the early placentas showed numerous syncytial sprouts, most of which represent stages in the formation of new free or terminal villi.     

Placental pathology in women with type 1 diabetes and in a control group with normal and large-for-gestational-age infants

Unexplained intra-uterine fetal death is still a problem in diabetic pregnancies, especially in those with an LGA-infant. We hypothesized that in these pregnancies impaired placental function, in terms of abnormal placental weight and/or abnormal placental histology, may account for this phenomenon. To test this hypothesis, we assessed the relative placental weight and scored several histological abnormalities in 34 AGA- and 24 LGA-placentae of type 1 diabetic women and in 22 AGA- and 16 LGA-placentae of control women. Relative placental weight was comparable in the LGA-diabetic cases and in the control groups, but was significantly higher in the AGA-diabetic subgroup. Histological abnormalities such as the presence of nucleated fetal red blood cells, fibrinoid necrosis, villous immaturity and chorangiosis were observed more often in the diabetic placentae compared with the control placentae. These differences in histology were particularly observed when we compared both AGA-groups. LGA-control placentae showed a high incidence of histological abnormalities, almost comparable to the diabetic placentae. Only fibrinoid necrosis was significantly more common in the LGA-diabetic placentae. Three of the four cases of perinatal death/asphyxia in the diabetic group concerned an LGA-infant with a relative low placental weight. In conclusion, placentae of women with type 1 diabetes showed several abnormalities that can be associated with impaired functioning. The difference between AGA- and LGA-diabetic placentae was related to relative placental weight and our data suggest that an increase in relative weight may protect the fetus from asphyxia. Placentae from LGA-non-diabetic women showed several similarities to those of women with diabetes.     

Granulated metrial gland cells in the mouse placenta

A study has been made of granulated metrial gland (GMG) cells and adjacent layer 1 cytotrophoblast in the labyrinthine placenta of the mouse. In those cellular associations in which both cell types appeared healthy with the light microscope, examination with the electron microscope identified features which may form part of the early stages in the interaction which can occur between GMG cells and some layer 1 trophoblast. These included microvillous processes from each cell forming an interdigitating network, a polarization of mitochondria in a GMG cell with interdigitating microvilli, platelets, and some GMG cells which appeared to form a specialized cell junction with a small lymphocyte. The latter observation indicates that a tripartite functional relationship may exist between lymphocytes, GMG cells and layer 1 labyrinthine trophoblast. In a quantitative analysis of GMG cells in the maternal blood spaces of placentae no significant differences in the numbers of GMG cells present in these spaces or involved in an interaction with layer 1 labyrinthine trophoblast were detected between inbred and outbred pregnancies. These results suggest that histocompatibility antigens are not significant factors in determining the frequency of interactions between GMG cells and trophoblast.     

Placentation in the Hottentot Golden Mole,Amblysomus hottentotus (Afrosoricida: Chrysochloridae)

The placentation of the Hottentot golden mole (Amblysomus hottentotus) has been examined using light and electron microscopy and lectin histochemistry of nine specimens at both mid and late gestation. The placentae were lobulated towards the allantoic surface and the lobules contained roughly parallel arrays of labyrinthine structures converging on a central spongy zone. At mid gestation, the arrays were composed of an inner cellular and outer syncytial trophoblast layer, the inner layer enclosing scant connective tissue and fetal capillaries. Maternal blood spaces coursed through the outer trophoblast and were lined by trophoblastic microvilli; the blood spaces were narrow in mid gestation but enlarged near term, while the inner trophoblast layer became thinner and seemed to be syncytial. These features were confirmed by transmission electron microscopy. The microvillous surfaces and dispersed cytoplasmic particles were heavily glycosylated, as shown by lectin histochemistry, and exhibited changes with maturation, particularly a loss in N-acetyl glucosamine oligomers bound by Phytolacca americana lectin on the microvilli lining the maternal blood spaces and outer trophoblast particles. A substantial yolk sac was present both in mid and late gestation stages. It was clearly unattached to the uterus in the later stages. These morphological features are discussed in relation to the phylogenetic position of Amblysomus with respect to other members of Afrosoricida and Afrotheria.     

Morphological aspects of the placenta in HIV pregnancies

Forty-nine placentae from HIV-seropositive mothers were collected in various hospitals in France and Belgium. Twenty [corrected] placentae with seven fetuses from interrupted pregnancies and 29 [corrected] placentae from spontaneous deliveries, including two stillborns and a set of twins, were studied morphologically. No significant abnormalities were observed in the aborted material. The placentae corresponding to deliveries presented no significant gross abnormalities but the ratio of fetal to placental weight was significantly decreased in the study group compared with the control group (6.13 versus 7.41; P less than 0.001), associated with a congestive and mature aspect of the parenchyma. Histologically a high incidence of chorioamnionitis (43 per cent) was found, contrasting with the absence of villitis. A relative villous hypercellularity was observed in the study group compared with the control group. Ultrastructural studies of 13 placentae corresponding to gestations of 10 to 40 weeks are presented. In six cases, retrovirus-like particles were found at various sites, such as villous fibroblasts, syncytiotrophoblast and endothelial cells, and in the free membranes.     

Quantitative structural studies on placentas from pregnancies complicated by diabetes mellitus

Fourteen placentas from pregnancies complicated by insulin-dependent diabetes mellitus have been examined by quantitative morphometry. The results have been compared with those from 22 placentas of comparable gestation from uncomplicated pregnancies. The volume of parenchymatous tissue in the placentas from diabetic mothers was significantly increased while the volume of nonparenchyma was decreased. The villous surface area was increased in placentas from the diabetic group, the mean value being 17.3 m2 compared with the 11.4 m2 of the normal group. This increase was larger than would be expected when the increase in fetal weight of some babies born to diabetic mothers is taken into account.     

Quantitative structural studies on placentas from pregnancies complicated by diabetes mellitus

Summary. Fourteen placentas from pregnancies complicated by insulin-dependent diabetes mellitus have been examined by quantitative morphometry. The results have been compared with those from 22 placentas of comparable gestation from uncomplicated pregnancies. The volume of parenchymatous tissue in the placentas from diabetic mothers was significantly increased while the volume of non-parenchyma was decreased. The villous surface area was increased in placentas from the diabetic group, the mean value being 17·3 m² compared with the 11·4 m²of the normal group. This increase was larger than would be expected when the increase in fetal weight of some babies born to diabetic mothers is taken into account.     

Placental folate transport and binding are not impaired in pregnancies complicated by fetal growth restriction

Maternal folate deficiency is associated with fetal growth restriction, however, transfer of folate across placentae of pregnancies complicated by fetal growth restriction has never been investigated. We studied whether maternal to fetal 5-methyltetrahydrofolate (5MTF) transport in the ex vivo dually perfused isolated cotyledon, binding of [(3)H] folate (PteGlu) to the syncytial microvillous membrane, and protein expression of folate receptor alpha (FR-alpha) and reduced folate carrier (RFC) in these placentae are disturbed. Placental clearance of 5MTF from the maternal perfusate appeared to be non-saturable over a range of 50 to 500 nm, independent of albumin and flow-independent. No statistically significant differences between placentae complicated with fetal growth restriction and uncomplicated pregnancies were observed. Binding characteristics of [(3)H-]PteGlu to microvillous membranes of fetal growth restriction versus control placentae were similar: B(max)of 3.9+/-2.0 (mean+/-s.d.) versus 4.0+/-1.6 pmol/mg protein and a K(d)of 0.037+/-0.010 versus 0.040+/-0.018 nm. Expression of FR-alpha and RFC were not different in placentae of both groups studied. In conclusion, fetal growth restriction appears not to be associated with impaired maternal to fetal placental folate transport, placental receptor binding, or expression of FR-alpha and RFC.     

Relation between placental morphometry and fetal growth]

Forty-eight placentae of full term infants, 21 placentae from appropriate for gestational age infants (AGA) and 27 placentae from small for gestational age infants (SGA) were measured by morphometric technic using the automatic image analyzer, in order to find out the extent of fetomaternal exchange which determines the transfer of oxygen and nutrition from mother to fetus and fetal growth. The results of measurement correlated well both with infant birth weight and placental weight. They demonstrated striking quantitative differences when the placentae of SGA were compared with those of AGA. The placenta weights in the group of SGA were notably less than those in the group of AGA. It seems that low birth weight relates to low functional tissue mass of placenta. This reduction of functional tissue is accompanied by diminution of the area for exchange between mother and fetus, both at the villous surface area and at fetal capillary surface area. Thus, the ability of transferring oxygen and nutrition from mother to fetus is curtailed. The results show that the rate of fetal growth is limited by placental function as well as its weight.