MORPHOFUNCTIONAL PECULIARITIES OF THE PLACENTA IN WOMEN WITH UNDIFFERENTIATED CONNECTIVE TISSUE DYSPLASIA SYNDROME.

OBJECTIVE: The aim: The impact of undifferentiated connective tissue dysplasia on the formation of the placenta. PATIENTS AND METHODS: Materials and methods: The morphostructure of 50 placentas with the undifferentiated connective tissue syndrome and 50 placentas of women with physiological pregnancy and absence of connective tissue pathology was studied. RESULTS: Results: The results of morphological studies have shown that the main pathogenetic link of placental dysfunction with highly resistant blood flow in the umbilical arteries in pregnant women with undifferentiated connective tissue dysplasia syndrome is a disorder of functional differentiation of the villous tree.In these cases the dominats were large and medium-sized villi with narrowed lumen in arterial, venular and capillary vessels and arterial spasm and venous plethora, as well as with numerous chaotically sclerosed villi, indicating stage I and II of placental. There is a large amount of fibrins in intervillous space which narrows it and leads to violation of microcirculation and placenta tissue hypoxia. CONCLUSION: Conclusions: The morphological basis of high flow resistance in the umbilical artery with the undifferentiated connective tissue dysplasia syndrome in pregnant women is a pathological immaturity of the placental villous tree. Morphological study of the architecture of the stem and intermediate placental villi revealed a violation of the structure of collagen fibers in the form of lack of crosslinks of bundles of collagen fibers.

Disorders of placental villous maturation are present in one-third of cases with spontaneous preterm labor.

OBJECTIVES: Spontaneous preterm labor is an obstetrical syndrome accounting for approximately 65-70% of preterm births, the latter being the most frequent cause of neonatal death and the second most frequent cause of death in children less than five years of age worldwide. The purpose of this study was to determine and compare to uncomplicated pregnancies (1) the frequency of placental disorders of villous maturation in spontaneous preterm labor; (2) the frequency of other placental morphologic characteristics associated with the preterm labor syndrome; and (3) the distribution of these lesions according to gestational age at delivery and their severity. METHODS: A case-control study of singleton pregnant women was conducted that included (1) uncomplicated pregnancies (controls, n=944) and (2) pregnancies with spontaneous preterm labor (cases, n=438). All placentas underwent histopathologic examination. Patients with chronic maternal diseases (e.g., chronic hypertension, diabetes mellitus, renal disease, thyroid disease, asthma, autoimmune disease, and coagulopathies), fetal malformations, chromosomal abnormalities, multifetal gestation, preeclampsia, eclampsia, preterm prelabor rupture of the fetal membranes, gestational hypertension, gestational diabetes mellitus, and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome were excluded from the study. RESULTS: Compared to the controls, the most prevalent placental lesions among the cases were the disorders of villous maturation (31.8% [106/333] including delayed villous maturation 18.6% [62/333] vs. 1.4% [6/442], q<0.0001, prevalence ratio 13.7; and accelerated villous maturation 13.2% [44/333] vs. 0% [0/442], q<0.001). Other lesions in decreasing order of prevalence included hypercapillarized villi (15.6% [68/435] vs. 3.5% [33/938], q<0.001, prevalence ratio 4.4); nucleated red blood cells (1.1% [5/437] vs. 0% [0/938], q<0.01); chronic inflammatory lesions (47.9% [210/438] vs. 29.9% [282/944], q<0.0001, prevalence ratio 1.6); fetal inflammatory response (30.1% [132/438] vs. 23.2% [219/944], q<0.05, prevalence ratio 1.3); maternal inflammatory response (45.5% [195/438] vs. 36.1% [341/944], q<0.01, prevalence ratio 1.2); and maternal vascular malperfusion (44.5% [195/438] vs. 35.7% [337/944], q<0.01, prevalence ratio 1.2). Accelerated villous maturation did not show gestational age-dependent association with any other placental lesion while delayed villous maturation showed a gestational age-dependent association with acute placental inflammation (q-value=0.005). CONCLUSIONS: Disorders of villous maturation are present in nearly one-third of the cases of spontaneous preterm labor.

Morphometric Parameters of Placental Villi in Parturient Women with COVID-19.

We performed a comparative morphological analysis of placental villi in parturient women with mild and moderate COVID-19 infection. The area and perimeter of terminal villi, their capillaries, and syncytiotrophoblast were assessed on immunohistochemical preparations with antibodies to CD31 using an image analysis system; the parameters of fetal vascular component in the placental villi were also assessed. Changes in the studied parameters differed in parturient women with mild and moderate COVID-19 infection. The observed increase in the total perimeter with a simultaneous decrease in the total capillary area and the degree of vascularization of the placental villi in parturient women with COVID-19 indicates impairment of circulation in the fetal compartment and the development of placental hypoxia, which can be the cause of unfavorable neonatal outcomes.

The Use of Atomic Force Microscopy in Comprehensive Assessment of the "Mother-Placenta-Fetus" System in Obstetric and Endocrine Pathology during Pregnancy.

Atomic force microscopy is not very popular in practical health care, therefore, its potential is not studied enough, for example, in obstetrics when studying the "mother-placenta-fetus" system. Our study summarizes the possibilities of using atomic force microscopy for detection of various circulatory disorders and vascular changes at the microscopic level in the uterus (endometrium and myometrium), placenta, and umbilical cord in the main variants of obstetric and endocrine pathology. For instance, in the case of endocrine pathologies, changes in the form of stasis, sludge, diapedesis, ischemia, destruction and separation of endotheliocytes in villous blood vessels were found in the mother. The oxygen content in erythrocytes also naturally decreased in pathologies; poikilo- and anisocytosis were observed.

Peculiarities of RIG-1 Expression in Placental Villi in Preeclampsia.

The expression of RIG-1 in placenta samples was assessed in women of reproductive age with early- and late-onset preeclampsia and cesarean delivery at 27-39 weeks of gestation. The highest expression of RIG-1 was found in the syncytiotrophoblast of placental villi in the group with uncomplicated full-term pregnancy (normal); RIG-1 expression in groups with early- and late-onset preeclampsia was significantly (p<0.01) lower. In decidual cells, RIG-1 expression was also maximum in normal pregnancy and significantly (p<0.01) lower in lateonset preeclampsia. In the endothelium of villous capillaries, the maximum expression was observed in normal full-term pregnancy and in late-onset preeclampsia, while in early-onset preeclampsia this parameter was significantly (p<0.01) lower. It can be assumed that different variants of preeclampsia are mediated by similar pathogenetic mechanisms, including those related to immature molecular profile of the trophoblast and decidual cells, probably due to impaired stem cell activity in the placenta determining higher vulnerability and reduced regeneration capacity of the placental tissue. This is due to the fact that RIG-1 is one of the important signaling molecules that promote activation of stem cell and tissue regeneration.

Placental Stem Villus Arterial Remodeling Associated with Reduced Hydrogen Sulfide Synthesis Contributes to Human Fetal Growth Restriction.

Intrauterine fetal growth restriction (IUGR) is often associated with compromised umbilical arterial flow, indicating increased placental vascular resistance. Oxidative stress is causatively implicated. Hydrogen sulfide maintains differentiated smooth muscle in vascular beds, and its synthetic enzyme cystathionine-γ-lyase (CSE) is down-regulated in growth-restricted placentas. We hypothesized that remodeling of resistance arteries in stem villi contributes to IUGR by compromising umbilical blood flow via oxidative stress, reducing hydrogen sulfide signaling. Stem villus arteries in human IUGR placentas displaying absent or reversed end-diastolic flow contained reduced myosin heavy chain, smooth muscle actin, and desmin, and increased markers of dedifferentiation, cellular retinol-binding protein 1, and matrix metalloproteinase 2, compared to term and preterm controls. Wall thickness/lumen ratio was increased, lumen diameter decreased, but wall thickness remained unchanged in IUGR placentas. CSE correlated positively with myosin heavy chain, smooth muscle actin, and desmin. Birth weight correlated positively with CSE, myosin heavy chain, smooth muscle actin, and desmin, and negatively with cellular retinol-binding protein 1 and matrix metalloproteinase 2. These findings could be recapitulated in vitro by subjecting stem villus artery explants to hypoxia-reoxygenation, or inhibiting CSE. Treatment with a hydrogen sulfide donor, diallyl trisulfide, prevented these changes. IUGR is associated with vascular remodeling of the stem villus arteries. Oxidative stress results in reduction of placental CSE activity, decreased hydrogen sulfide production, and smooth muscle cell dedifferentiation in vitro. This vascular remodeling is reversible, and hydrogen sulfide donors are likely to improve pregnancy outcomes.

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells.

OBJECTIVE: Biglycan (BGN) has reduced expression in placentae from pregnancies complicated by fetal growth restriction (FGR). We used first trimester placental samples from pregnancies with later small for gestational age (SGA) infants as a surrogate for FGR. The functional consequences of reduced BGN and the downstream targets of BGN were determined. Furthermore, the expression of targets was validated in primary placental endothelial cells isolated from FGR or control pregnancies. APPROACH AND RESULTS: BGN expression was determined using real-time polymerase chain reaction in placental tissues collected during chorionic villous sampling performed at 10 to 12 weeks' gestation from pregnancies that had known clinical outcomes, including SGA. Short-interference RNA reduced BGN expression in telomerase-immortalized microvascular endothelial cells, and the effect on proliferation, angiogenesis, and thrombin generation was determined. An angiogenesis array identified downstream targets of BGN, and their expression in control and FGR primary placental endothelial cells was validated using real-time polymerase chain reaction. Reduced BGN expression was observed in SGA placental tissues. BGN reduction decreased network formation of telomerase-immortalized microvascular endothelial cells but did not affect thrombin generation or cellular proliferation. The array identified target genes, which were further validated: angiopoetin 4 (ANGPT4), platelet-derived growth factor receptor α (PDGFRA), tumor necrosis factor superfamily member 15 (TNFSF15), angiogenin (ANG), serpin family C member 1 (SERPIN1), angiopoietin 2 (ANGPT2), and CXC motif chemokine 12 (CXCL12) in telomerase-immortalized microvascular endothelial cells and primary placental endothelial cells obtained from control and FGR pregnancies. CONCLUSIONS: This study reports a temporal relationship between altered placental BGN expression and subsequent development of SGA. Reduction of BGN in vascular endothelial cells leads to disrupted network formation and alterations in the expression of genes involved in angiogenesis. Therefore, differential expression of these may contribute to aberrant angiogenesis in SGA pregnancies.

Association of Placental Jets and Mega-Jets With Reduced Villous Density.

Spiral arteries (SAs) lie at the interface between the uterus and placenta, and supply nutrients to the placental surface. Maternal blood circulation is separated from the fetal circulation by structures called villous trees. SAs are transformed in early pregnancy from tightly coiled vessels to large high-capacity channels, which is believed to facilitate an increased maternal blood flow throughout pregnancy with minimal increase in velocity, preventing damage to delicate villous trees. Significant maternal blood flow velocities have been theorized in the space surrounding the villi (the intervillous space, IVS), particularly when SA conversion is inadequate, but have only recently been visualized reliably using pulsed wave Doppler ultrasonography. Here, we present a computational model of blood flow from SA openings, allowing prediction of IVS properties based on jet length. We show that jets of flow observed by ultrasound are likely correlated with increased IVS porosity near the SA mouth and propose that observed mega-jets (flow penetrating more than half the placental thickness) are only possible when SAs open to regions of the placenta with very sparse villous structures. We postulate that IVS tissue density must decrease at the SA mouth through gestation, supporting the hypothesis that blood flow from SAs influences villous tree development.

Autism risk classification using placental chorionic surface vascular network features.

BACKGROUND: Autism Spectrum Disorder (ASD) is one of the fastest-growing developmental disorders in the United States. It was hypothesized that variations in the placental chorionic surface vascular network (PCSVN) structure may reflect both the overall effects of genetic and environmentally regulated variations in branching morphogenesis within the conceptus and the fetus' vital organs. This paper provides sound evidences to support the study of ASD risks with PCSVN through a combination of feature-selection and classification algorithms. METHODS: Twenty eight arterial and 8 shape-based PCSVN attributes from a high-risk ASD cohort of 89 placentas and a population-based cohort of 201 placentas were examined for ranked relevance using a modified version of the random forest algorithm, called the Boruta method. Principal component analysis (PCA) was applied to isolate principal effects of arterial growth on the fetal surface of the placenta. Linear discriminant analysis (LDA) with a 10-fold cross validation was performed to establish error statistics. RESULTS: The Boruta method selected 15 arterial attributes as relevant, implying the difference in high and low ASD risk can be explained by the arterial features alone. The five principal features obtained through PCA, which accounted for about 88% of the data variability, indicated that PCSVNs associated with placentas of high-risk ASD pregnancies generally had fewer branch points, thicker and less tortuous arteries, better extension to the surface boundary, and smaller branch angles than their population-based counterparts. CONCLUSION: We developed a set of methods to explain major PCSVN differences between placentas associated with high risk ASD pregnancies and those selected from the general population. The research paradigm presented can be generalized to study connections between PCSVN features and other maternal and fetal outcomes such as gestational diabetes and hypertension.

Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects.

BACKGROUND: The uteroplacental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. OBJECTIVE: We demonstrate the feasibility of the use of contrast-enhanced ultrasound imaging to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. STUDY DESIGN: Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n = 6/group). Human subjects were recruited immediately before scheduled first-trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition with a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion. RESULTS: In macaques, the rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and heat shock protein 70 as markers of apoptosis, nitrative, and oxidative stress, respectively, were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11 weeks gestation, and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast after first-trimester ultrasound studies. CONCLUSIONS: Use of contrast-enhanced ultrasound did not result in placental structural damage and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound imaging may offer a safe clinical tool for the identification of pregnancies that are at risk for vascular insufficiency; early recognition may facilitate intervention and improved pregnancy outcomes.

A multiscale model of placental oxygen exchange: The effect of villous tree structure on exchange efficiency.

The placenta is critical to fetal health during pregnancy as it supplies oxygen and nutrients to maintain life. It has a complex structure, and alterations to this structure across spatial scales are associated with several pregnancy complications, including intrauterine growth restriction (IUGR). The relationship between placental structure and its efficiency as an oxygen exchanger is not well understood in normal or pathological pregnancies. Here we present a computational framework that predicts oxygen transport in the placenta which accounts for blood and oxygen transport in the space around a placental functional unit (the villous tree). The model includes the well-defined branching structure of the largest villous tree branches, as well as a smoothed representation of the small terminal villi that comprise the placenta's gas exchange interfaces. The model demonstrates that oxygen exchange is sensitive to villous tree geometry, including the villous branch length and volume, which are seen to change in IUGR. This is because, to be an efficient exchanger, the architecture of the villous tree must provide a balance between maximising the surface area available for exchange, and the opposing condition of allowing sufficient maternal blood flow to penetrate into the space surrounding the tree. The model also predicts an optimum oxygen exchange when the branch angle is 24 °, as villous branches and TBs are spread out sufficiently to channel maternal blood flow deep into the placental tissue for oxygen exchange without being shunted directly into the DVs. Without concurrent change in the branch length and angles, the model predicts that the number of branching generations has a small influence on oxygen exchange. The modelling framework is presented in 2D for simplicity but is extendible to 3D or to incorporate the high-resolution imaging data that is currently evolving to better quantify placental structure.

[Massive perivillous fibrin deposition, chronic histiocytic intervillositis and villitis of unknown etiology: Lesions of the placenta at the fetomaternal interface with risk of recurrence]. / Massive perivillöse Fibrinabscheidungen, chronisch-histiozytäre Intervillositis, Villitis unbekannter Ätiologie : Plazentaläsionen bei Störungen der fetomaternalen Einheit mit Rezidivrisiko.

BACKGROUND: Maternal floor infarction/massive perivillous fibrin deposition (MFI/MFD), chronic histiocytic intervillositis (CHIV) and villitis of unknown etiology (VUE) are lesions of the placenta which are characterized morphologically. The cause is thought to be pathological immunotolerance/rejection reaction at the fetomaternal interface. The risk of recurrence is elevated and the lesions can lead to severe pediatric diseases. AIM: This article provides an overview of the pathological and anatomical characteristics of each of these lesions, including diagnostic criteria, suspected etiology, clinical relevance and suggested therapy options. MATERIAL AND METHODS: A selective search of the literature was carried out and experiences from own diagnostic clientele are presented. RESULTS AND DISCUSSION: While MFI/MFD and CHIV occur more rarely, VUE is relatively common occurring in up to 15 % of placentas at term. Both MFI/MFD and CHIV can occur in the first and second trimester, while VUE typically manifests in the third trimester. All lesions can lead to intrauterine growth retardation or abortion and have a tendency towards disease recurrence. Furthermore, VUE and MFI/MFD can be associated with an adverse neurodevelopmental outcome in the children. For all these entities potential therapy strategies have been reported, which are mainly based on anticoagulation and immunosuppression in subsequent pregnancies.

Massive perivillous fibrin deposition in the placenta and uterine metastasis of gastric adenocarcinoma during pregnancy.

The prognosis of gastric cancer during pregnancy is unfavorable because of delayed diagnosis and advanced stage. We present a case of gastric carcinoma metastasized to the placenta and uterus during pregnancy. Pathological examination revealed a poorly differentiated adenocarcinoma of the stomach with lymph node metastasis. After counseling, the patient decided to terminate the pregnancy and begin immediate treatment for gastric cancer. Hysterectomy and subtotal hysterectomy were performed because medical termination of the pregnancy was unsuccessful. Pathological examination of the placenta and uterus revealed metastases of gastric adenocarcinoma. All the uterine vessels were packed with tumor cells and the myometrium showed extensive coagulative necrosis. Moreover, microscopic findings of the placenta were consistent with massive perivillous fibrin deposition. Our case clearly suggests that massive perivillous fibrin deposition in the placenta can be associated with malignancy during pregnancy and that uterine metastasis of maternal malignancy may result in myometrial dysfunction unresponsive to uterotonics.

Post-partum hemorrhage and malpractice claims: what can we learn from the findings of placental examination and endometrial curettage? A retrospective analysis of surgical pathology reports.

OBJECTIVE: This study reviews the surgical pathology reports of post-partum hemorrhages to support clinicians in malpractice litigation and, potentially, to enhance pregnancy-related diagnoses. STUDY DESIGN: This work is a retrospective study of surgical pathology reports of term pregnancies between January 2000 and January 2012 selected from the Surgical Pathology database of the I.R.C.C.S Azienda Ospedaliera Universitaria San Martino-IST (Istituto Nazionale per la Ricerca sul Cancro, Genoa). RESULTS: Ninety-five revision reports were identified (0.22% "placenta accrete," 0.46% "non-accreta placental tissue retention," and 0.31% "no placental fragments retention"). Secondary post-partum hemorrhages occurred in 0.3%, and primary PPH occurred in 0.05%, regardless of the group examined. Both types of PPH were most often associated with vaginal deliveries (58%). The most frequent endometrial finding was post-partum endometritis (43%). The entire placenta was submitted to the pathologist in 22/95 cases (23%). Hypermaturity and/or villous immaturity were the main histological patterns. CONCLUSIONS: This review supports the hypothesis that the pathological placenta abnormalities observed, rather than underlying myometrium abnormalities, may underlie the contractile failure and the incomplete removal of the placenta. For these reasons, the authors emphasized the importance of investigating the placenta in cases of complicated deliveries not associated with PPH to support clinicians in malpractice claims.

[Expression and regulatory mechanism of microRNA-155 in the villi of patients with unexplained recurrent spontaneous abortion patients].

OBJECTIVE: To study the expression and the mechanism of miR-155in the villi of patients with unexplained recurrent spontaneous abortion (URSA). METHODS: The expression of miR-155 in the villi of 36 cases with URSA (URSA group) and 25 women with normal early pregnancy (control group) were detected by stem-loop real-time reverse transcription (RT) qPCR.Expression of hypoxia inducible factor-1 (HIF-1α), vascular endothelial cell growth factor (VEGF) and micro lymphatic vessel density (MVD) in the villi of were measured by immnohistochemical staining among two groups. RESULTS: (1)miR-155 expression:the mean miR-155 expression were 1.456 (0.489, 2.459) in URSA group and 2.833 (1.740, 3.794) in control group, which reached statistical difference (P < 0.05). The mean expression of miR-155 of 1.683 (0.902, 2.459) in URSA group with abortion times ( ≤ 3) was significantly higher than 1.229 (0.489, 1.719) in URSA group with more than 4 times abortion (P < 0.05). (2) Indexes :the expression of HIF-1α, VEGF and MVD value were 121 ± 12, 134 ± 12, 36 ± 6 in URSA group and 99 ± 10, 109 ± 10, 28 ± 4 in control group, which reached statistical difference (P < 0.01). The expression of HIF-1α, VEGF and MVD value of 119 ± 12, 134 ± 12, 35 ± 5 in URSA group with less than 3 times abortion was significantly lower than 128 ± 12, 138 ± 12, 43 ± 6 in URSA group with more than 4 times abortion (P < 0.01). CONCLUSIONS: The expression of miR-155 and HIF-1α is topically stimulated by oxygen signal.HIF-1α adjusts the transcription and translation of VEGF, which together involved in placental trophoblast invasion and placental angiogenesis. The low expression of miR-155 could interfere with expression of HIF-1α and VEGF, which might be involved in villous vascular dysplasia in URSA.

Influence of maternal anemia during pregnancy on placenta and newborns.

INTRODUCTION: Sideropenic anemia is a common pregnancy disorder. Depending on severity, maternal anemia can significantly influence morphometric characteristic of placental tissue, pregnancy course and outcome. OBJECTIVES: to estimate if maternal anemia a) results with significant placental changes; b) influence on newborn weight, length and vitality. PATIENTS MATERIAL AND METHODS: Research included 100 women and their newborns, 50 anemic, and 50 women in the control group. Sixty placentas were collected, placental mass and volume was determined, and blood vessels of terminal villi were stereologically analyzed. Newborns mass and body length, and Apgar scores within 1 and 5 minutes after delivery were recorded. THE RESULTS: Placentas of anemic pregnant women showed significant increase of terminal villi blood vessels (224,18 vs. 197,00 cm(3); p<0,0001), but total placental mass and volume did not differ significantly. Anemic mothers' newborns were significantly shorter (51,76 vs. 55,54 cm; p<0,0001), smaller body mass (3048,00 vs. 3615,60 g; p<0,0001) and delivered one week early (38,2 vs. 39,2 GW; p<0,0001), but not significantly poorer vitality (p>0,05) comparing with the control group. CONCLUSION: Sideropenic anemia increase placental maturity, that could be a possible cause of earlier spontaneous delivery among anemic women. The anemic mothers' newborns are shorter and lower body mass, but not poorer vitality index.

Timing of Histological Distal Villous Fetal Vascular Malperfusion in the Placenta: Clinical Significance and Placental Features.

OBJECTIVE: This retrospective analysis compares the diagnostic value of placental large vessel (global, partial) and distal villous (complete, segmental) fetal vascular malperfusion (FVM), remote/established, recent and on-going. METHODS: 24 independent abnormal clinical and 46 placental phenotypes were retrospectively statistically analyzed among 1002 consecutive cases, mostly with congenital anomalies in which CD34 immunostaining was performed. Group A: 398 cases without distal FVM and none or up to two large vessels FVM lesions. Group B: 221 cases with distal villous FVM without clustered endothelial fragmentation by CD34 immunostain. Group C: 145 cases with clustered endothelial fragmentation by CD34 immunostain but no clustered sclerotic or mineralized distal villi. Group D: 163 cases with coexistence of distal villous lesions of Group B and Group C. Group E: 75 cases with three or four lesions of large vessel FVM, but no distal villous FVM lesions. RESULTS: Established and/or remote FVM had clinical/placental associations similar to those of recent FVM, but on-going FVM was most commonly high grade and associated with preterm pregnancies, stillbirth, and fetal growth restriction. Large vessel FVM usually occurs in advanced third trimester pregnancies with fetal congenital anomalies, villitis of unknown etiology, and intervillous thrombi but no direct association with abnormal fetal condition. CONCLUSION: FVM was the most common pattern of placental injury in this material. Proximal FVM was more common than distal FVM, suggesting the sequence of occurrence and the likely umbilical cord compression etiology. CD34 immunostaining doubles the sensitivity of placental examination and frequently upgrades the FVM, making it an important adjunct to placental histology.

Chorionic villous vascularization related to phenotype and genotype in first trimester miscarriages in a recurrent pregnancy loss cohort.

STUDY QUESTION: Is there an association between chorionic villous vascularization, ultrasound findings and corresponding chromosome results in early miscarriage specimens from a cohort of recurrent pregnancy loss patients? SUMMARY ANSWER: We did not find a significant difference in vascularization scores of chorionic villi between embryonic, yolk sac or empty sac miscarriages, or between euploid and noneuploid miscarriages. WHAT IS KNOWN ALREADY: At least half of first trimester miscarriages are due to embryopathogenesis associated with chromosome errors and/or major congenital anomalies, resulting in an empty sac, a yolk sac or an embryonic miscarriage. Absent and decreased chorionic villous vascularization is usually present in these pregnancies. STUDY DESIGN, SIZE, DURATION: For this retrospective study, 60 hematoxylin and eosin slides of miscarriage tissue of less than 10 weeks gestational age were collected from an academic institution. All patients were seen in consultation between July 2004 and October 2009. PARTICIPANTS, SETTING, METHODS: Chorionic villous vascularization was determined using a previously published classification. The results were validated and compared with the ultrasound findings and corresponding chromosome results. MAIN RESULTS AND THE ROLE OF CHANCE: There were 53 embryonic miscarriages, 5 yolk sac miscarriages and 2 empty sac miscarriages. Chromosome results were obtained in 59 of the 60 miscarriages; 37.3% were euploid and 62.7% were noneuploid. Validation of the vascularization score between observers was reasonable to good (Kappa 0.47-0.76), and 59% of the cases were classified as avascular. The vascularization score did not differ between euploid or noneuploid miscarriages, or between embryonic, yolk sac or empty sac miscarriages. Avascular villi were seen more frequently in miscarriages trisomic for chromosome 16, when compared with miscarriages with other trisomies (6 out of 7 versus 8 out of 22, P = 0.04). LIMITATIONS, REASONS FOR CAUTION: Unfortunately, the number of samples in the study was limited. WIDER IMPLICATIONS OF THE FINDINGS: Avascular villi may indicate abnormal early placentation as a part of embryopathogenesis. Further study is warranted to determine whether a genetic cause can be found to explain these results.

Morphological characteristics of the terminal villi in placental failure.

A comparative morphological study of the placentas in spontaneous and induced pregnancy aggravated by placental failure was carried out. Placental failure manifested by shrinkage of the terminal villi, lesser number and section areas of their capillaries, and higher expression of vascular endothelium growth factor and endothelial NO synthase in the syncytiotrophoblast and villous endotheliocytes. The changes were more pronounced in pregnancy developing after in vitro fertilization.

Abnormal expression of SLIT3 induces intravillous vascularization dysplasia in ectopic pregnancy.

Objective: To investigate whether the morphology, capillary number, and transcriptome expression profiles of ectopic pregnancy (EP) villi differ from those of normal pregnancy (NP) villi. Methods: Hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining for CD31 were conducted to compare differences in morphology and capillary number between EP and NP villi. Differentially expressed (DE) miRNAs and mRNAs were determined from transcriptome sequencing of both types of villi and used to construct a miRNA-mRNA network, from which hub genes were identified. Candidate DE-miRNAs and DE-mRNAs were validated by quantitative reverse transcription (qRT)-PCR. Correlations were identified between the number of capillaries and serum beta human chorionic gonadotropin (ß-HCG) levels and between the expression levels of hub genes associated with angiogenesis and ß-HCG levels. Results: The mean and total cross-sectional areas of placental villi were significantly increased in EP compared with NP villi. Capillary density was greatly reduced in EP villi and was positively correlated with ß-HCG levels. A total of 49 DE-miRNAs and 625 DE-mRNAs were identified from the sequencing data. An integrated analysis established a miRNA-mRNA network containing 32 DE-miRNAs and 103 DE-mRNAs. Based on the validation of hub mRNAs and miRNAs in the network, a regulatory pathway involving miR-491-5p-SLIT3 was discovered, which may have a role in the development of villous capillaries. Conclusion: Villus morphology, capillary number, and miRNA/mRNA expression profiles in villous tissues were aberrant in EP placentas. Specifically, SLIT3, which is regulated by miR-491-5p, may contribute to the regulation of villous angiogenesis and was established as a putative predictor of chorionic villus development, providing a basis for future research.