Terminal Villous Research Articles

Multi-type maternal diabetes mellitus affects human placental villous geometric morphology: A three-dimensional imaging study

IntroductionDiabetes mellitus leads to maldevelopment of the villous morphology in the human placenta, disrupting the exchange of materials between the maternal and fetal compartments, consequently compromising fetal development. This study aims to explore how different types of diabetes mellitus affect human placental villous geometric morphology including branching numbers and sizes (length, diameter). MethodsHere an optical coherence tomography (OCT)-based 3D imaging platform was utilized to capture 3D images of placental villi from different types of diabetes, including type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). ResultsDifferent types of diabetes mellitus exhibit different effects on human placental villous geometric morphological parameters: GDM had greater placenta villous parameters at intermediate villous diameter (IVD), terminal villous diameter (TVD), terminal villous length (TVL) compared to the healthy, T1DM, and T2DM, and these differences were statistically significant. The TVD of T1DM and T2DM had significantly greater sizes than the healthy. There was no statistically significant difference in the number of villous branches among the three types of diabetes, but T1DM and GDM had more villous branches than healthy individuals. DiscussionDiabetes mellitus affects the geometric morphology of human placental villi, with varying effects observed in pregnancies of different diabetes types. These findings offer a novel avenue for exploring underlying pathophysiological mechanisms and enhancing the management of women with diabetes from preconception through pregnancy.

Morphometric Analysis of Placental Terminal Villi, Capillaries, and Intervillous Space in Normal and Pre-Eclamptic Pregnancies

Background: The placenta reflects the prenatal problems that are linked to high perinatal morbidity and mortality both macroscopically and microscopically. A pregnancy syndrome called pre-eclampsia has terrible consequences for both the mother and the unborn child. It may result in more frequent inductions of labor, fetal growth limitation, respiratory issues in newborns, increased admission rates to neonatal critical care units, and an elevated risk of perinatal or fetal death. To understand the relation of preeclampsia and fetal growth identification of its effects on various components of the placenta is mandatory hence the current study was designed to evaluate the Placental Terminal Villi, Capillaries, and Intervillous Space in Normal and Pre-eclamptic Pregnancies. Methodology: It was a cross sectional study, carried out on 50 samples of placentas, out of which 25 were preeclamptic and 25 were normal. The placentas were recruited after cesarean session, processed as per guidelines and were analyzed for histopathological examination. The set inclusion criteria were Registered cases of Pre-eclampsia, Blood Pressure ≥ 140/90 mmHg, Parity 0 – 4, Age of mother (25 – 35) Years., Gestational Age (36 – 42) Weeks, Mode of delivery Cesarean Sections. The set exclusion criteria were known hypertensive patients, and patient diagnosed with other chronic illnesses. Results: Number of terminal villi, Transverse diameter of terminal villi (μm), Intervillous space (μm), and Transverse diameter of terminal villous capillaries decreased significantly (p=0.001) in preeclamptic group however, Number of terminal villous Capillaries were found to be increased in preeclamptic group (p=0.001). Conclusion: Preeclampsia leads to more significant alterations in placental structure compared to normal pregnancies, emphasizing the importance of early detection and management of this condition to improve maternal and fetal outcomes. Keywords: Pregnancy, preeclampsia, terminal villi, Intervillous space, terminal villous Capillaries

Serial block-face scanning electron microscopy reveals novel intercellular connections in human term placental microvasculature.

The placental microvasculature is a conduit for fetal blood allowing solute exchange between the mother and the fetus. Serial block‐face scanning electron microscopy (SBF SEM) allows ultrastructure to be viewed in three dimensions and provides a new perspective on placental anatomy. This study used SBF SEM to study endothelial cells within the human placental microvasculature from uncomplicated pregnancies. Term human placental villi were aldehyde‐fixed and processed for imaging by SBF SEM. Manual segmentation was carried out on a terminal villous capillary and an intermediate villous arteriole and venule. Twenty‐seven SBF SEM stacks from terminal villi were analysed using stereological approaches to determine the volumes of microvascular components and the proportions of pericyte coverage. SBF SEM analysis of capillary endothelial cells revealed the presence of interendothelial protrusions (IEPs) originating from the donor cell at the endothelial junction and forming deep thin projections up to 7 μm into the adjacent endothelial cells. IEP density was estimated to be in the order of 35 million cm–3 placental tissue. Pericytes cover 15% of the fetal capillary surface area in terminal villi. In comparison, the cytotrophoblast covered 24% of the syncytiotrophoblast basal membrane. A trans‐endothelial channel was observed in a region of the vasculo‐syncytial capillary. Pericyte coverage was extensive in both arteriole and venule. Three‐dimensional imaging of the placental microvasculature identified novel ultrastructural features and provided an insight into factors that may influence capillary permeability and placental function. We hypothesise that the IEPs may allow mechanosensing between adjacent endothelial cells to assist in the maintenance of vessel integrity. The numbers of endothelial junctions, the presence of trans‐endothelial channels and the extent of pericyte coverage all provide an insight into the factors determining capillary permeability.

Expression of e-NOS in Human Placentas of Idiopathic Intra Uterine Growth Restriction at Term

Endothelial nitric oxide synthase (e-NOS) is a chemical agent that involves in placental angiogenesis. It is conveyed through embryogenesis. In the contemporary study, we intended to examine the character of placental angiogenesis in the progress of intrauterine growth restriction (IUGR) by means of matching the levels of expression of e-NOS in normal-term pregnancy and IUGR placentas. Angiogenesis is one dominant factor in normal embryogenesis and hence the wellbeing of the newborn. The expression of e-NOS was planned using the streptavidin-biotin-peroxidase technique in placental tissues identified as normal (n = 33) and IUGR (n = 33) cases from mothers looking apparently normal. All were chosen at term pregnancy and obtained between 2nd of February of 2018 and 31th of January 2019 at selected hospitals. Outcomes were appraised semi-quantitatively. The expression of e-NOS marker as an immunohistochemistry total score and staining percentage were significantly greater (p < 0.05) in epithelial surface, smooth muscle cells of fetal vessels and the connective tissue terminal villous core of the IUGR placentas when matched with placentas collected from normal pregnancies at term. Encountered placental histochemical changes regarding the expression of the e-NOS angiogenic factor for idiopathic IUGR newborns raised the suspicion of that, it was caused by pure placental factors and could represent further requirement for Nitric Oxide to dilate fetal vessels to optimize functional requirement during placental insufficiency. The noticed Increased expression of e-NOS may be the result of inadequate uteroplacental perfusion supporting the proposal that abnormal angiogenesis plays a role in the pathophysiology of IUGR

Histomorphometrical Study of Placental from Male and Female Neonates of Diabetic Women

Objective: To investigate occur the histomatrical alternations in placental terminal villi and their vessels of Iraqi diabetes (gestational diabetes and overt diabetes) and normal pregnancies were born male and female neonates. Methods: The hitometrical study of male and female terminal villi of 68 placentae in maternal diabetes mellitus (34 gestational diabetes, 34 overt diabetes (17 DM type 1 and 17 DM type 2) and 34 normal placentae. These placentae obtained from Department of Obstetrics and Gynaecology in three hospitals in Baghdad city. Results: The study showed that there is a statistically significant with higher diameter in central and peripheral sections of the terminal villi and their vessels in male neonate. Moreover, terminal villous diameter in central and peripheral sections of placentae in both male and female neonates appeared highly significant differences (P≤0.001) between DM type 1 and DM type 2, but fetal blood vessels in this terminal villous did not record any significant difference (P>0.05). Conclusions: The current results concluded that increasing in diameters terminal villous and their fetal blood vessels of central and peripheral sections of placentae recorded increasing diameters of GDM peripheral sections of placentae in male neonate in comparison to placental sections of other study groups.

Angiogenesis in villous chorangiosis observed by ultrastructural studies

Chorangiosis is microscopically designated as more than ten terminal capillaries within the villous stroma of the placenta and is mostly related to chronic fetal hypoxia. However, the histogenetic relationship between increased number of terminal villous capillaries and chronic hypoxia has not yet been clarified. Of 665 placentas histologically examined at Saitama Medical University from 2003 to 2010, chorangiosis was found in 58 cases (8.7 %), which were mostly more than 35 gestational weeks. In addition, low birth weight (less than 2,500 g) infants (74.1 %) and those who suffered from cardiac anomalies, chromosome anomalies, and single umbilical artery comprised 32.7 % of cases. Placental lesions were associated with chorangiosis involved in infarct (46.6 %), intervillous thrombosis (20.7 %), and marginal hemorrhages (22.4 %). Scanning electron microscopic studies showed narrowing of vessel ostium and disorders of endothelium in the umbilical cord vessel complicated by chorangiosis. Furthermore, in transmission electron microscopic observation, not only the chorionic villi had multiple enlarged vessels within the villous stroma, but we also found that new capillaries were formed by angiogenesis with endothelial cells derived from fibroblasts under the chronic hypoxic state.

Stereological assessment of placental morphology in intrahepatic cholestasis of pregnancy

ObjectiveTo apply stereology for the detection of possibly morphological abnormalities in placentas of women with intrahepatic cholestasis of pregnancy (ICP). Study designProspective case-control study of placentas from untreated and UDCA-treated ICP, respectively, and normal pregnancies, examined for morphological differences by systematic random sampling generated by computerized stereology methodology. Main outcome measuresVolume of placenta, surface area of terminal villi and capillaries, volume fraction of collagen, number of syncytial knots, and chorangiosis. ResultsSurface area of terminal villi and capillaries, and number of syncytial knots were higher in placentas from all ICP, as compared to controls (p < 0.01). A reduction of collagen was found in placentas from UDCA-treated ICP, both in comparison to placentas from untreated ICP and controls (p < 0.05). ConclusionICP affects the placenta morphologically as shown by increased terminal villous and capillary surface area, and number of syncytial knots.

Morphometric analysis of terminal villi and gross morphological changes in the placentae of term idiopathic intrauterine growth restriction

The aim of this study is to compare the gross morphology of the placentae and the morphometry of terminal villi and terminal villous capillaries in pregnancies complicated by idiopathic intrauterine growth restriction (IUGR) with those of normal pregnancies. 75 placentae were collected between April 2010 and March 2011. 50 placentae were associated with idiopathic IUGR and 25 were from controls. Insertion of cords, placental weights and diameters were noted. Hematoxylin and eosin-stained wax sections were analyzed stereologically. Growth of terminal villi and fetal capillaries was assessed by estimating total and mean surface areas. Villous capillarization was monitored using capillary:villus surface ratio. Measurements were done using image analysis system. In comparison with the control group, idiopathic IUGR placentae are significantly smaller (p=0.000) and lighter (p=0.000). In majority of IUGR (68%) and control (60%) cases, eccentric insertion of cord is noted. In idiopathic IUGR group, there is a significant decrease in the total areas of both terminal villi (p=0.048) and their capillaries (p=0.000) and a significant decrease in number of both terminal villi (p=0.000) and their capillaries (p=0.001), also, capillarization index is significantly smaller (p=0.038). Idiopathic IUGR is associated with reduced growth of placental terminal villi and fetal capillaries and this is accompanied by changes in measures of villous capillarization as compared with those of control placentae. Further investigations of idiopathic IUGR placentae are necessary, especially considering the histopathological changes that could affect the fetomaternal exchange, with a note that strict distinction should be made between idiopathic and nonidiopathic IUGR placentae.

Structural analysis of human placental stem and terminal villi from normal and idiopathic growth restricted pregnancies

Studying in detail different histomorphological and pathological findings in placental stem and terminal villi of appropriate for gestational age (AGA) and idiopathic intrauterine growth restricted (IUGR) fetuses, then analyzing their correlation to the neonatal birth weight and to the some morphological features of the placenta. Fifty full-term human placentae of idiopathic IUGR and 25 of AGA pregnancies were processed for haematoxylin and eosin staining and evaluated by light microscope aided with Image Analyzer. The mean number of stem villous arteries, and the mean number of terminal villous capillaries per field are significantly lower in idiopathic IUGR group (4.63 ± 0.46, 47.09 ± 4.44, respectively) than in AGA group (12.36 ± 0.61, 73.35 ± 5.13, respectively) (p = 0.001). Both AGA and idiopathic IUGR placentae share the presence of many pathological features: (1) narrowing of stem villous arteries appears in 38 (76 %) of IUGR cases and in 9 (36 %) of AGA cases with significant difference between groups (p = 0.001); (2) cellular infiltration (villitis) of the stem villi is significantly higher in IUGR cases [24 (48 %)] than in AGA cases [2 (8 %)] (p = 0.001). The study shows significant correlation between the birth weight and different pathologic features in the stem villi as arterial number (r = 0.494; p = 0.000), arterial narrowing (r = 0.283, p = 0.004), degenerative changes (r = 0.331, p = 0.001) and villitis (r = 0.275, p = 0.005). There is also significant correlation between neonatal birth weight and terminal villous capillary number (r = 0.281, p = 0.001) but no significant correlation is found between the birth weight and terminal villous fibrotic changes (r = -0.098, p = 0.318). Histomorphological and pathological changes in the stem villi could explore the cause of idiopathic IUGR. Stem villous arterial number, arterial narrowing, degeneration and villitis could be underlying mechanisms. Further researches on the hormonal and cytokine level should be undertaken to demonstrate the precipitating factors of these changes and the possible preventing measures.

Placental Vascularization in Early Onset Small for Gestational Age and Preeclampsia

The objective was to determine whether chorionic villous vascularization is diminished in cases of early onset (<34 weeks) small for gestational age (SGA) and/or preeclampsia (PE). Placental morphometrical measurements were performed in 4 gestational-age-matched groups complicated by SGA, SGA with PE, PE, and spontaneous preterm delivery without SGA or PE as the reference group. Using a video image analysis system, in randomly selected intermediate and terminal villi, the stromal area and the following villous vascular parameters were manually traced and analyzed: number of total, centrally and peripherally localized vessels, vascular area, and vascular area density. No differences were observed in intermediate and terminal villous vascular area. Preeclampsia was associated with smaller terminal villous stromal area (reference 2299 μm2, SGA 2412 μm2, SGA + PE 2073 μm2, and PE 2164 μm2, P = .011), whereas SGA was associated with an increased terminal villous vascular area density (reference 26.1%, SGA 35.7%, SGA + PE 33.4%, and PE 32.0%, P = .029). Compared with preserved flow, lower terminal villous vascular area density was found in cases with absent or reversed end-diastolic (ARED) umbilical artery flow (39.3% vs. 30.3%, P = .013). These data demonstrate that villous vascularization was not influenced by PE, whereas in terminal villi an increased vascular area density was associated with SGA. Lower terminal villous vascular area density was associated with ARED flow in SGA pregnancies, indicating an increased risk of fetal compromise.

Stereology of the placenta in type 1 and type 2 diabetes

ObjectiveTo assess by stereology the placental structure in type 1 (T1DM) and type 2 (T2DM) diabetic pregnancies compared to normal non-diabetic (ND) controls. Study designProspective case control study. Placentae were sampled in a systematic random fashion. Stereological analysis was performed using a computerised stereology programme (Image Pro 6.2, Media Cybernetics, Inc, Silver Spring MD, USA). Participants were matched for gender of infant and mode of delivery. Main outcome measuresVolume, length and surface area of placental components; clinical outcome. ResultsTen ND, eight T2DM and ten T1DM women consented to the study. There was no difference between the groups regarding maternal age, neonatal birth weight, or placental weight. On stereological examination, terminal villous volume was significantly increased in both diabetic groups compared to ND controls. Capillary volume and length was increased in T1DM pregnancies compared to ND and T2DM. Capillary length was increased in both diabetic groups compared to ND. When all diabetic groups were compared based on severity of glycaemia those with poor glycaemic control (HbA1c>7%) had higher placental capillary volume than those with good glycaemic control. ConclusionsThis study demonstrates an association between maternal diabetes and increased terminal villous volume. Additionally capillary volume and length is increased in the placentae of normally grown infants of T1DM diabetic mothers compared to non-diabetic controls. Maternal glycaemia appears to influence capillary, but not stromal, development. This suggests that factors other than glycaemia have a role in placental development in pre-gestational diabetes.

Pre-eclampsia and Fetal Growth Restriction: How Morphometrically Different is the Placenta?

Both pre-eclampsia (PET) and fetal growth restriction (FGR) pose a heavy burden on fetal and maternal health and may disrupt pregnancy outcome. Using design based stereological techniques, placental vascular and villous morphology were assessed to determine the individual role played by both PET and FGR on placental growth during the third trimester. The following placentas delivered between 25 and 41 weeks of gestation were included into the study; controls (n=16), PET (n=20), FGR (n=17) and PET-FGR (n=16). Each placenta was uniformly randomly sampled and the sampled tissue processed to paraffin. Sections were stained with a CD34 antibody and the following morphometric parameters estimated: volumes, surface areas, length, diameters and the shape factor of the villous (terminal and intermediate) and vascular placental features. For stereologically estimated parameters pure PET had an effect on IVS and terminal villi volume only. FGR alone or when coexisting with PET contributed towards significant reductions in volumetric and surface area terminal villous and vascular features. FGR factors also contributed towards a significant reduction in the lengths of all parameters estimated and in the terminal villi diameter. Additionally, FGR was associated with a significant difference in shape factor indices for both intermediate and terminal villi. This study has shown that PET on its own has limited influence on the placental morphology studied, since the vascular features estimated do not differ stereologically from age matched normal controls. However, placental morphology is different between PET and PET-FGR and between PET-FGR and FGR. PET and FGR may have a cumulative effect on placental villous and vascular morphology as seen in the PET-FGR but there is no synergistic effect. These morphological abnormalities may have major physiological implications in terms of placental function and fetal growth.

Vasculogenesis, Angiogenesis and the Molecular Organisation of Endothelial Junctions in the Early Human Placenta

Vasculogenesis and angiogenesis are regulated by the capacity of endothelial cells to adhere to each other and form new tubes. The presence and role of junctional adhesion molecules during physiological vasculogenesis is unknown. Using ultrastructural and immunocytochemical approaches, we compared the junctional phenotype of developing vessels of the first-trimester human placenta with vessels in the last trimester; the latter include newly formed terminal capillaries and the quiescent vascular bed. First-trimester placental vessels contained the adherens junctional molecules, vascular endothelial cadherin and α- and β-catenin but lacked plakoglobin, the component of fully differentiated adherens junctions. Furthermore, these vessels did not contain the transmembrane tight junctional molecules occludin and claudin-1 and -2. This profile reflects the phenotype of terminal capillaries but differs from large vessels of the full-term placenta. Electron microscopic studies revealed that endothelial tight junctions are present in the first-trimester placenta. Thus, occludin and claudin-1 appear to play no part in the formation of endothelial tight junctions, but are a later requirement. In the early placenta, the predominant growth factor appears to be vascular endothelial growth factor (VEGF), whilst at term, angiopoietin-1 was present in large vessels, with intense angiopoietin-2 immunofluorescence (and VEGF) located in terminal villous capillaries. Thus, endothelial junctions in the human placenta possess two distinct molecular phenotypes, i.e. stable or dynamic, dependent on maturity and plasticity. These distinct phenotypes may be influenced by the angiopoietins/VEGF present in the placenta.

Endothelial phenotype of the materno–fetal barrier

The terminal villous capillaries of the human placenta are the sites of maximal materno‐fetal exchange. These capillaries are highly angiogenic and are formed in the last trimester of pregnancy by looped angiogenesis from existing microvessels in the intermediate villi. They represent an ‘activated’ phenotype by possessing adherens junctions which contain VE‐cadherin (– and (– catenin but lack plakoglobin, the component of well differentiated junctions. The tight junctions present here show negative immunoreactivity to occludin and claudin‐1. The conduit vessels further upstream in the stem villi have the full complement of adherens and tight junctional molecules. VEGF and angiopoietin‐2 is present in terminal villi whilst angiopoietin‐1 appears to be a predominant feature of stem villi. The phenotype of junctions present in nascent vessels of the first trimester placentae was similar to the angiogenic terminal villous capillaries. The predominant growth factor here was VEGF, localised to all villi. Isolation of endothelial cells from last trimester placenta microvessels (HPMEC) demonstrated that these cells are capable of differential expression and dynamic regulation of cell‐cell junctions. Cells grown in the presence of ECGS showed a reduction in the level and junctional localisation of plakoglobin and occludin, with associated increased permeability to macromolecules. These adhesion molecules were up‐regulated and targeted back to cell‐cell contact regions by growing HPMEC in the presence of cAMP enhancing agents. This resulted in a 1.7 times increase in transendothelial resistance whilst proliferation of HPMEC cells was inhibited by elevated cAMP. HUVEC cells isolated from the umbilical cords of these placentae contain the full repertoire of AJ molecules in normal culture conditions with no change in composition or resistance under elevated cAMP. The differential expression of junctional adhesion molecules along the placental vascular tree and their in vitro plasticity suggests there is a physiological relevance of junctional regulation in the placenta. The activated junctional phenotype of the newly formed terminal microvessels allows them to participate in increased growth, proliferation and solute exchange in the last trimester when fetal demand is at its greatest. Furthemore, this necessary junctional immaturity of new/angiogenic human vessels appear to be at the expense of barrier function.Funded by the Wellcome Trust.

Pseudo-partial moles: placental stem vessel hydrops and the association with Beckwith-Wiedemann syndrome and complete moles.

To describe the clinical and histological features of a series of cases of placentas originally diagnosed as partial moles in which the final diagnosis was that of placental stem villous hydrops, mesenchymal dysplasia or Beckwith-Wiedemann syndrome. We searched a computerized database containing cases of suspected or proven trophoblastic disease examined at the Trophoblastic Disease Unit at Charing Cross Hospital, London, to identify cases in which stem vessel hydrops was present without other histological features of partial mole. For each case, histological sections were examined and the histological features present recorded. There were 15 cases identified. Placental weight was above the 95th centile of the normal for gestation in all cases in which this information was documented. In an additional five cases the placenta was described as 'large'. All cases had marked stem vessel hydropic change with cyst formation and in the majority of cases some terminal villous hydrops was also present. In 13 of the 15 cases there was marked aneurysmal dilatation of stem villous vessels. Nine had focal chorioangiomatoid change and in four of these extramedullary haematopoiesis was focally present in these areas. No excessive trophoblast proliferation was noted in any case and no trophoblastic inclusions typical of partial mole were identified. This study has identified cases of stem villous hydrops, mesenchymal dysplasia or Beckwith-Wiedemann spectrum in pregnancies initially diagnosed as partial hydatidiform mole in the second half of pregnancy and has highlighted the need for detailed pathological examination and clinicopathological correlation in all such cases.

Immuno-electron Microscopic Localization of Endothelial Nitric Oxide Synthase in Human Placental Terminal Villous Trophoblasts—Normal and Pre-eclamptic Pregnancy

We demonstrated the subcellular localization of endothelial nitric oxide synthase (eNOS) in human placental terminal villous trophoblasts at near term period, and compared the distribution pattern with that in pre-eclamptic trophoblasts, using immunogold electron microscopy. Immunolabelling for eNOS was visible markedly in the syncytial microvilli and syncytial cytoplasm. Semiquantitative analysis showed that the concentration and the distribution pattern of gold particles for eNOS did not significantly differ between normal and pre-eclamptic placental trophoblasts. These results indicated that syncytiotrophoblastic microvilli and cytoplasm were the subcellular localization sites of syncytium-derived eNOS in terminal villi, and that there were no significant differences in this eNOS subcellular distribution pattern between normal and pre-eclamptic syncytiotrophoblasts in regard to immunohistochemically detectable eNOS.

Molecular Organization of Tight and Adherens Junctions in the Human Placental Vascular Tree

Tight and adherens junctions are major determinants of endothelial integrity. Molecules present therein have been implicated in vascular permeability, stability of junctions, angiogenesis and intracellular signalling. Using immunofluorescence and confocal scanning microscopy, the adherens junctions (AJs) in human placental vessels were found to contain the entire cadherin–catenin complex predicted from in vitro studies. Vascular endothelial cadherin (VE-cadherin) clusters were co-localized with β-catenin, an important signal transduction ligand, and with α-catenin, which is thought to link the complex to the peri-junctional actin. Antibodies to plakoglobin, a molecule shown to be a component of stable adherens junctions, revealed immunoreactivity in clefts of stromal villous vessels, but weak or negative immunoreactivity in intermediate and terminal villi. Tight junctional molecules demonstrated a differential surface expression. Within the same villous tree, arteries, veins and arterioles contained occludin but the exchange vessels in terminal villi were immunonegative. ZO-1, however, was present throughout. Ultrastructurally, there were no differences in frequency, position or dimension of tight junctions in these vessels. They showed a consistent 4nm separation between outer membrane leaflets regardless of their location in the vascular tree. Occludin is not necessary for formation of tight junctions in the placenta; it may have an accessory role providing stability or added adhesiveness to tight junctions of large vessels. Its absence in terminal villous microvessels, along with the weak plakoglobin immunoreactivity in AJs, suggest that the junctions here are less stable. This may allow the increased plasticity necessary in terminal villi for continual growth, proliferation and solute exchange.

Glucose metabolism is elevated and vascular resistance and maternofetal transfer is normal in perfused placental cotyledons from severely growth-restricted fetuses.

We hypothesized that placental resistance was elevated and transfer reduced in cotyledons from intrauterine growth-restricted (IUGR) fetuses. We perfused 10 cotyledons from term, normally grown fetuses, six from preterm, normally grown fetuses with normal umbilical arterial end-diastolic velocities (EDV), and six from preterm IUGR fetuses (<3rd centile) with absent or reversed umbilical arterial EDV. Perfused cotyledons were pressure-fixed, and villi were observed by scanning electron microscopy. The groups did not differ in fetoplacental resistance at baseline; neither did they differ in the change in resistance that followed the administration of nitroglycerin or angiotensin II. The increase in resistance during hypoxia was similar in the two preterm groups but greater in the term than in the preterm normally grown group (p < 0.05). Groups did not differ in net maternofetal transfer of oxygen or glucose, or in clearance of aminoisobutyric acid or antipyrine. However, glucose consumption was doubled in cotyledons of preterm IUGR versus preterm normally grown fetuses (p < 0.05). Terminal villi of perfused cotyledons from preterm IUGR fetuses displayed less terminal villous branching and budding than preterm controls, as anticipated from previous work. IUGR fetuses with absent or reversed umbilical arterial EDV in vivo may have high placental resistance due to a vasoconstrictive rather than anatomic abnormality and an elevated placental glucose consumption that may impair glucose transfer.

Adaptive Angiogenesis in Placentas of Heavy Smokers

Maternal smoking in pregnancy has been associated with both impaired fetal growth and perinatal deaths, suggesting abnormal placental function. The placenta, however, is disproportionately large in smokers at the time of delivery. It seemed possible that, because smoking reduces oxygen transport by increasing carboxyhemoglobin, placental enlargement might be a result of adaptive angiogenesis in the placental villi. The authors prepared plastic injection casts of the fetal capillaries within placental cotyledons, taking specimens from elective cesarean deliveries at 38 to 40 weeks’ gestation. Four women who had smoked more than one pack a day throughout pregnancy and four nonsmokers were included in the study. Low-power microscopic study of the casts suggested increased capillary density within the terminal capillary convolutes in women who smoked (Fig. 1). Higher magnification disclosed increased branching within the terminal capillary loops in specimens from smokers. Both elongated and compact types of angiogenesis were observed. These findings point to an adaptive response of the fetal capillary bed within the placental villi of smokers, a change that should increase the surface area for diffusional exchange and thereby offset the impaired oxygen transport caused by carbon monoxide displacing oxygen from hemoglobin in maternal and fetal blood. Fig. 1: Representative scanning electronmicrograph images of terminal villous capillaries from nonsmoking (A, ×4700) and smoking (B, ×3760;C, 4700) placentas. Branches (arrowheads) and sinusoidal dilations (stars) are indicated. Note dense capillary network (C) and a high degree of coiling (B). VC = venous capillary. Reproduced with permission of The Lancet Ltd.Stopping smoking may be an important way of preventing perinatal death in women who are otherwise at low risk. It possibly would help to use a visual approach when trying to persuade women of the dangers of smoking while pregnant. They could be shown how the placenta tries to maintain oxygen transfer to the developing fetus. Lancet 1999;354:303

Pathologic findings in pregnancies with unexplained increases in midtrimester maternal serum human chorionic gonadotropin levels.

Second trimester maternal serum human chorionic gonadotropin (MShCG) levels are commonly obtained as part of a screening protocol for chromosomal anomalies. Approximately 4% to 6% of patients have elevated hCG levels for gestational age, and this test has been reported to identify a group at risk for pregnancy complications. We ascertained 24 patients with unexplained elevated MShCG levels and available placental pathology among 5,790 deliveries during a 58-week period and compared them with 48 controls with normal MShCG levels delivering during the same period. Cases had a higher prevalence of preeclampsia, intrauterine growth retardation, and preterm delivery. Pathology in cases included more large-for-gestational-age placentas, fewer small-for-gestational-age placentas, lower mean fetoplacental weight ratios, more decidual plasma cell infiltrates, and more retroplacental hematomas. Other more frequent abnormalities that did not reach statistical significance included abnormal placental shape and chronic villitis. Maternal and fetal vascular abnormalities were similar in both groups. Morphometric analysis were performed on hCG-immunostained sections from placentas at 17, 21, 36, and 41 weeks' gestation. Patients with elevated MShCG showed an increased volume of hCG-positive trophoblast per unit surface area and increased intensity of hCG immunoreactivity within individual terminal villous units.