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.

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.

The role of ß-HCG and VEGF-MEK/ERK signaling pathway in villi angiogenesis in patients with missed abortion.

OBJECTIVE: To analyze the effects of the Human Chorionic Gonadotropin beta (ß-hCG) and the VEGF-MEK/ERK signaling pathway on villi angiogenesis in early missed abortion. METHODS: A total of 12 cases of women with missed abortion and 12 cases of women who had induced abortion voluntarily without any disease were included in the present study. The age, pregnancy time and gestation period in the control group corresponded to the missed abortion group. Wes Simple Western system and qRT-PCR were used to detect the expression of VEGF-MEK/ERK signaling pathway related proteins and genes in villous. Radioimmunoassay and Enzyme-linked immunosorbent assay were used to detect ß-hCG and VEGF levels in serum. The microvascular density (MVD) in villous tissue was analyzed by immunohistochemical staining. RESULTS: The levels of ß-hCG and VEGF in serum, the expression of VEGF-MEK/ERK signaling pathway and MVD in villous tissue of the missed abortion group were lower than those of the control group. In addition, compared with the control group, the layers of trophoblasts of the villous tissue in the missed abortion group became thinner significantly, the number of cells reduced, the cell structures were disorganized, and parts of the trophoblast cells were absent. Correlational analysis showed that the protein expression of ERK1/2 was positively correlated with MVD in missed abortion group. CONCLUSIONS: Our results reveal that decreased production of ß-hCG in early pregnant women could down-regulate the expression of VEGF-MEK/ERK signal pathway, then reduce angiogenesis and eventually leading to the abnormal angiogenesis of villous, which may be an important mechanism of missed abortion.

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.

Investigating human placentation and pregnancy using first trimester chorionic villi.

Chorionic villus sampling (CVS), routinely used for prenatal diagnosis of cytogenetic disorders, also possesses great potential for the study of placentation. To better understand villus biology, human placentation, and how these relate to pregnancy outcomes, we examined the morphology and transcriptomes of villi obtained via CVS from 10 to 14 weeks of pregnancy and correlated these with pregnancy attributes and clinical outcomes. First, we established a morphological scoring system based on three main villus features: branching, budding and vascularization. We then tested whether morphology scores were predictive of pregnancy attributes and clinical outcomes. Finally, we used RNA sequencing to assess the transcriptional basis of villus morphology and tested the hypothesis that gene expression may predict pregnancy outcomes. We demonstrate that villus morphology varies tremendously between patients, irrespective of gestational age, and that transcriptional differences are highly predictive of villus morphology. We show that pre-eclampsia markers are associated with villi with low morphology scores. Additionally, we identify SVEP1 as a possible biomarker for defining gestational age. Overall, chorionic villi in the first trimester remain one of the few means to correlate placental function with pregnancy outcome and these samples are a valuable and increasingly rare resource.

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.

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.

Placental Villous Vascularity Is Decreased in Premature Infants with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension.

The development of pulmonary hypertension (PH) is a serious complication of bronchopulmonary dysplasia (BPD) among infants born at extremely low gestational ages. Bronchopulmonary dysplasia-associated PH is characterized by persistent pulmonary vasoconstriction, progressive right heart dysfunction, and an increased risk of death. We have shown previously that certain placental vascular lesions are associated with BPD-associated PH. Further evaluation of the villous and vascular morphometry of these placentas is warranted. Using digital image analysis (DIA), we compared villous and vascular morphometric parameters of placentas from infants with and without BPD-associated PH. We conducted a case-control study of placentas from 14 infants born at ≤28 weeks' gestational age (GA). Cases with PH (N=7) and non-PH controls (N=7) were identified using echocardiogram screening at 36 weeks' corrected GA. Central parenchymal sections from each placenta were stained for CD31. Digital image analysis was used to measure vessel and villous capillary number, perimeter, diameter, and area. Mean villous vascularity (number of vessels per villus) was calculated for each patient. Mean vessel and villous number as well as area were similar between the two groups. Villous vascularity was decreased in placentas from infants who ultimately had PH disease compared to non-PH controls (5.5±1.0 vs 7.1±1.6; P<0.05). Placental villous vascularity is decreased in infants with BPD-associated PH. Further studies should assess whether placental morphometric markers may allow clinicians to better predict BPD and provide earlier and more targeted management.

Defective pericyte recruitment of villous stromal vessels as the possible etiologic cause of hydropic change in complete hydatidiform mole.

The pathogenetic mechanism underlying the hydropic change in complete hydatidiform moles (CHMs) is poorly understood. A growing body of data suggests that pericytes play a role in vascular maturation. Since maturation of villous stromal vessels in CHMs is markedly impaired at early stages, we postulated that a defect in pericytes around stromal vessels in chorionic villi might cause vascular immaturity and subsequent hydropic change. To investigate this, we examined several markers of pericytes, namely, α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-ß (PDGFR-ß), and desmin, in 61 normally developing placentas and 41 CHMs with gestational ages of 4-12 weeks. The ultrastructure of villous stromal vessels was also examined. Mature blood vessels from normal placentas show patent vascular lumens and formed hematopoietic components in the villous stroma. α-SMA and PDGFR-ß expression in the villous stroma gradually increased and extended from the chorionic plate to peripheral villous branches. The labeled cells formed a reticular network in the villous stroma and, after week 7, encircled villous stromal vessels. In comparison, α-SMA and PDGFR-ß expression in the villous stroma and stromal vessels of CHMs was significantly lower (p<0.05). Ultrastructurally, endothelial cells in villous stromal vessels in normal placentas were consistently attached by pericytes after week 7 when the vessels formed distinct lumen, whereas the villous stromal vessels in CHMs consisted of linear chains of endothelial cells, often disclosing primitive clefts without hematopoietic cells inside, and neither pericytes nor basal lamina surrounded the endothelial cells at any gestational age studied. This suggests that pericytes recruitment around villous stromal vessels is defective in CHMs and links to the persistent vascular immaturity of the villous stroma in CHMs, which in turns leads to hydropic villi.

Placental mesenchymal dysplasia, a case of intrauterine sudden death.

Placental mesenchymal dysplasia (PMD) is a rare condition presenting with enlarged, multicystic placenta like molar changes. Although PMD usually features a normal fetus and the pregnancy often extends into the third trimester, PMD is clinically significant lesion with high rates of FGR, IUFD, and is associated with Beckwith-Wiedemann syndrome (BWS). We report a 30-year old woman at her first pregnancy with intrauterine sudden death at 31 weeks of gestation. The vesicular lesion in her uterus was detected at 10 weeks on ultrasound. The fetus was normal size without any anomaly on ultrasound and normal trophoblastic vascularization by Doppler study during the pregnancy. As the pregnancy advanced, the vesicular lesion decreased in size and no fetal abnormalities were detected. At 28 weeks of gestation an ultrasound detected dilated periumbilical chorionic vessels. We didn't detect severe FGR or abnormal trophoblastic vascularization. At 31 weeks of gestation an intrauterine sudden death of a normal-sized fetus without any anomaly occurred. The placenta was enlarged, and microscopic morphology confirmed a diagnosis of PMD. The chorionic vessels were cirsoid, dilated and tortuous. We determined the rupture of expanded periumbilical chorionic vessels led to fetal death.

[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.

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.

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.

Association of Dll4/notch and HIF-1a -VEGF signaling in the angiogenesis of missed abortion.

BACKGROUND: Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in missed abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in missed abortion. METHODS: Women with missed abortion (n=27) and healthy controls (n=26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry. RESULTS: Compared with induced abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in missed abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in missed abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in missed abortion. Both in induced abortion and missed abortion, Dll4 was positively correlated with Notch1. CONCLUSIONS: The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in missed abortion.

Decidua parietalis-derived mesenchymal stromal cells reside in a vascular niche within the choriodecidua.

Mesenchymal stromal cells (MSCs) from gestational tissues represent promising cell populations with stem cell-like properties for use in regenerative medicine. Previously, we reported that MSCs in the chorionic villi of the human placenta reside in a vascular niche. However, the niche(s) in which MSCs reside in the fetal membranes, another rich source of MSCs, remains to be determined. The cell surface markers STRO-1 and 3G5 were previously employed to identify niches in a variety of tissues and here we use these markers to report the location of the MSC niche in the human decidua parietalis. The cultured decidua parietalis MSCs (DPMSCs) isolated from the choriodecidua component of the fetal membranes possessed stem cell-like properties such as adherence to plastic, colony forming ability, and multipotent differentiation potential. Fluorescence in situ hybridization analysis showed cultured DPMSCs were of maternal origin. Immunocytochemistry demonstrated that cultured DPMSCs stained positively with stem cell surface markers 3G5, CD105, CD106, STRO-1, CD146, CD49a, and α-SMA but were negative for hematopoietic markers (CD117, CD34) and vascular markers (CD34, von Willebrand factor [vWF]). Immunohistochemistry with antibodies to stem cell surface markers and the endothelial markers on term fetal membranes revealed a vascular niche for DPMSCs, which was confirmed by immunofluorescence analysis. Both STRO-1 and vWF fluorescence signals showed substantial overlap, while CD146 and vWF signals showed partial overlap. These observations were consistent with a vascular niche.

A comparison of in vitro culture of fetal nucleated erythroblasts from fetal chorionic villi and maternal peripheral blood for noninvasive prenatal diagnosis.

OBJECTIVE: We tested the feasibility of the in vitro culture of fetal nucleated erythroblasts from maternal blood for noninvasive prenatal screening as a substitute for culturing fetal nucleated erythroblasts from fetal villi. METHOD: Nucleated blood cells separated via Percoll from 52 samples of fetal villi and maternal peripheral blood were cultured with or without magnetic-activated cell sorting glycophorin A (MACS-GPA+), and detected by an anti-hemoglobin-epsilon (FITC) antibody. Gender of the epsilon-positive cells were identified by FISH and further confirmed by PCR of the villi karyotype. Developmental stages of nucleated erythroblasts from villi and blood with MACS-GPA+ were analyzed by Wright-Giemsa staining. RESULTS: In the maternal blood, epsilon-positive cells were found in 4 and 24 cultured samples with and without MACS-GPA+, respectively. Also, Y-signals were visualized in 3 out of 4 and in 15 out of 24 cases in the epsilon-positive cells. Although epsilon-positive cells were found in all villus samples irrespective of MACS-GPA+ sorting, Y-signals were visualized in 31 out of 52 cases. Proerythroblasts and basophilic erythroblasts occupied 7 and 1% in fetal and maternal samples (with MACS-GPA+), respectively. CONCLUSIONS: The in vitro culturing of fetal nucleated erythroblasts from maternal blood is not feasible with the current techniques for prenatal diagnosis, because the fetal nucleated erythroblast is not well developed in vitro. This may be attributed to the low proportion of these erythroblasts at an early stage in the fetal circulation and the low permeability of these cells to the maternal blood.

The effect of smoking on early chorionic villous vascularisation.

The aim of the study was to investigate whether first trimester chorionic villous vascularisation is different in women who smoked cigarettes before and during pregnancy in comparison with women who did not smoke. Placentas of smoking (>10 cigarettes/day, n = 13) and non-smoking women (n = 13), scheduled for a legal termination of a viable first trimester pregnancy for social indications, were retrieved. Placental tissues of 3-5 mm³ were whole mount CD31 immunofluorescence stained. Images of the CD31 immunofluorescence and contour of the villi were captured using an Optical Projection Tomography scanner. An immersive BARCO virtual reality system was used to create an enlarged interactive 3-dimensional hologram of the reconstructed images. Automatic volume measurements were performed using a flexible and robust segmentation algorithm that is based on a region-growing approach in combination with a neighbourhood variation threshold. The villous volume, vascular volume and vascular density were measured for the total chorionic villous tree as well as for its central and peripheral parts. No differences in maternal age and gestational age were found between non-smoking and smoking women. No differences were found in the total, central and peripheral villous tree volume and vascular volume. The central (13.4% vs. 9.5%, p=0.03) and peripheral (8.4% vs. 6.4%, p=0.02) villous tree vascular densities were increased in the smoking women as compared with the non-smoking women. In conclusion, chorionic villous vascularisation is already altered in first trimester of pregnancy in women who smoked cigarettes before and during pregnancy.

Placental chorangiosis: the association with oxidative stress and angiogenesis.

BACKGROUND/AIMS: Chorangiosis is considered to be strongly associated with fetal, maternal, and placental disorders, and has been found to be correlated with increased fetal morbidity and mortality. In this study, it is aimed to investigate the association of angiogenesis and oxidative stress with the pathogenesis of chorangiosis. METHODS: Expressions of heat shock protein 70 (HSP70), vascular endothelial growth factor-A (VEGF-A) and basic fibroblast growth factor (b-FGF), which are investigated with avidin-biotin-peroxidase method in formalin-fixed, paraffin-embedded sections from placental tissues diagnosed as no chorangiosis (n = 18) and chorangiosis (n = 18), have been evaluated in a semiquantitative manner. RESULTS: There were significant differences between chorangiosis and no chorangiosis cases with respect to birth weight, birth length, and Apgar scores (p < 0.001). Statistically significant (p < 0.001), diffuse and strong expressions with HSP70, VEGF-A and b-FGF were observed in the villous tissue of placental chorangiosis cases when compared with no chorangiosis cases. CONCLUSION: The majority of the chorangiosis cases had an accompanying poor perinatal outcome, and also those with accompanying angiogenesis and increased oxidative stress demonstrated diffuse and strong expressions of HSP70, VEGF-A and b-FGF. The interaction of maternal, placental, and fetal factors with increased oxidative stress and angiogenesis may possibly contribute to this arising pathologic change.

Vessel remodelling, pregnancy hormones and extravillous trophoblast function.

During early human pregnancy, extravillous trophoblast (EVT) cells from the placenta invade the uterine decidual spiral arterioles and mediate the remodelling of these vessels such that a low pressure, high blood flow can be supplied to the placenta. This is essential to facilitate normal growth and development of the foetus. Defects in remodelling can manifest as the serious pregnancy complication pre-eclampsia. During the period of vessel remodelling three key pregnancy-associated hormones, human chorionic gonadotrophin (hCG), progesterone (P(4)) and oestradiol (E(2)), are found in high concentrations at the maternal-foetal interface. Potentially these hormones may control EVT movement and thus act as regulators of vessel remodelling. This review will discuss what is known about how these hormones affect EVT proliferation, migration and invasion during vascular remodelling and the potential relationship between hCG, P(4), E(2) and the development of pre-eclampsia.

Morphology and morphometric analysis of stromal capillaries in full term human placental villi of smoking mothers: an electron microscopic study.

OBJECTIVES: The capillaries of placental villi play a very important role in the feto-maternal exchange of gases and nutrients. A morphological change in their structure may lead to the impairment of placental function. In this study an attempt has been made to find out the morphological and morphometric features of the capillaries in full term placental villi of non smoking mothers as well as active and passive smoking mothers under an electron microscope. MATERIALS AND METHODS: A total number of 163 placentae from active, passive and nonsmoking mother (n = 61+42+60) were processed for electron microscopic study. The ultrathin sections were examined under electron microscope and images were recorded. Morphometry and statistical analysis were carried out with the help of software. RESULTS: The study revealed that the endothelial cells of stromal capillaries of the placental villi were oedematous and the cytoplasm was rich in dilated endoplasmic reticulum, mitochondria, fibrils and fine filaments in both groups of the smokers' placenta in comparison to control. Morphometric analysis showed a significant reduction in the perimeter of the stromal capillary of the tertiary villi of placenta in both active and passive smokers from mean value of 71.65 ± 47.82 µ to mean value of 59.77 ± 29.72 µ (p = 0.07) and 49.49 ± 20.94 µ (p = 0.0005) respectively. In case of passive smoker, area of the capillary (µm²) reduced significantly (p = 0.00004) from mean value of 266.29 ± 331.86 µm² to 116.64 ± 83.62 µm² whereas the number of capillary per villus increased significantly (p = 0.046) from mean value 2.42 ± 1.84 to 4.2 ± 3.16. The thickness of basement membrane of the endothelial cells of stromal capillaries of the placenta increased significantly in active as well as passive smokers (p = 0.00001). CONCLUSIONS: The ultrastructural changes noticed in the endothelial cells of placental villi may be due to hypoxia resulting from tobacco consumption either in active or passive form by the pregnant mothers. Thus, targeted therapy may be implicated for hypoxia, which is one of the major cause of the life threatening disorders of pregnancy.