Expression of sirtuin 2 and 7 in placenta accreta spectrum.

OBJECTIVE: This study aimed to investigate the expression levels of sirtuin 2 and sirtuin 7 in the placenta accreta spectrum to reveal their role in its pathogenesis. METHODS: A total of 30 placenta accreta spectrum, 20 placenta previa, and 30 controls were experienced. The sirtuin 2 and sirtuin 7 expression levels in the placentas of these groups were determined by Western blot. sirtuin 2 and sirtuin 7 serum levels in the maternal and fetal cord blood were examined by enzyme-linked immunosorbent assay. RESULTS: It was found that sirtuin 7 in placenta accreta spectrum was significantly lower in the placenta compared to the control and placenta previa groups (p<0.05). However, a significant difference was not observed between the sirtuin 2 and sirtuin 7 levels in the maternal and fetal cord serum samples of those three groups (p>0.05). CONCLUSION: Sirtuin 7 may play an important role in the formation of placenta accreta spectrum. The effect of decreased expression of sirtuin 7 might be tissue-dependent in the placenta accreta spectrum and needs to be investigated further.

Elevated Expression of ADAMTS-12 in Maternal and Umbilical Cord Serum of Placenta Accreta Spectrum.

OBJECTIVE: We investigated a disintegrin and metalloproteinase with thrombospondin type 1 motif-12 (ADAMTS-12) levels in both fetal umbilical cord and maternal blood of pairs diagnosed with placenta accreta spectrum (PAS). METHOD: We analyzed ADAMTS-12 level by ELISA in 160 samples that included 30 control pairs (30 maternal and 30 umbilical cord serums), 20 pairs in the placenta previa (PP), and 30 pairs in the PAS group (30 maternal and 30 umbilical cord serums). RESULTS: There were increased serum levels of ADAMTS-12 in maternal serum (p = 0.037) and umbilical cord serum level (p = 0.004) of PAS group compared with the PP and healthy control groups. There was a positive correlation between maternal ADAMTS-12 and fetal ADAMTS-12 serum levels (r = 0.53, p = 0.002). CONCLUSION: Our findings indicate that ADAMTS-12 could be a -diagnostic biomarker for PAS.

Expression of NF-κB and VEGF in normal placenta and placenta previa patients.

BACKGROUND: Placenta previa is a pregnancy condition associated with the development of complications related to placental insufficiency, including hypertension, preeclampsia and perinatal mortality. Dysfunction in uteroplacental arteries causes the release of cytokines, leukotrienes and immunomodulatory hormones, which leads to an inflammatory reaction. OBJECTIVES: The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and vascular endothelial growth factor (VEGF) are known to play crucial roles in inflammation and angiogenetic regulation. This study aimed to demonstrate the morphometric and immunohistochemical effects on inflammation and angiogenesis underlying placenta previa. MATERIAL AND METHODS: Twenty pregnant patients with placenta previa and 20 healthy pregnant patients, all between 30 and 38 weeks gestational age, were included in the study. The gestational age of the pregnancies was determined according to the last date of menstruation and/or ultrasonographic measurements. Blood samples and clinical data were obtained from the prenatal patient groups. Samples were taken from the connecting stem region from both groups. RESULTS: The mean difference between the control and placenta previa patients was statistically significant for the parameters of blood vessels in villi, diameter of floating small villus, decidual cells, syncytial knots, congestion in blood vessels, fibrinoid accumulation, and inflammation. Significant degeneration and apoptotic changes in the syncytial cells of the root villi and an increase in syncytial nodes and bridges were observed in the placenta previa specimens. In the connecting stem region of the placenta previa samples, blood vessel dilatation, endothelial cell hyperplasia and a higher number of syncytial nodes were observed. In the immunohistochemical examination of the placenta previa samples, an increase in NF-κB and VEGF expression was observed in the endothelial cells, syncytial cells and Hofbauer cells. CONCLUSIONS: Vascular endothelial growth factor was found to stimulate endothelial cell proliferation and migration, and to significantly affect angiogenesis during the developmental process of the placenta and remodeling of the uterine vessels, inducing NF-κB signaling and apoptotic development during cytotrophoblastic invasion in the vascularization of the placenta.

Distinguishing placenta accreta from placenta previa via maternal plasma levels of sFlt-1 and PLGF and the sFlt-1/PLGF ratio.

INTRODUCTION: Our study aimed to distinguish patients with placenta accreta (crete, increta, and percreta) from those with placenta previa using maternal plasma levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PLGF) and the sFlt-1/PLGF ratio. METHODS: We obtained maternal plasma from 185 women in late pregnancy and sorted them into three groups: 72 women with normal placental imaging results (control group), 50 women with placenta previa alone (PP group), and 63 women with placenta previa and placenta accreta (PAS group). The concentrations of sFlt-1 and PLGF in the maternal plasma were measured using ELISA kits and the sFlt-1/PLGF ratio was calculated. RESULT: The median (min-max) sFlt-1 levels and the sFlt-1/PLGF ratio in the PAS group (12.8 ng/ml, 3.8-34.2 ng/ml) (133, 14-361) were lower than in the PP group (28.7 ng/ml, 13.1-60.3 ng/ml) (621, 156-2013) (p < 0.0001 and P < 0.0001, respectively). The median (min-max) PLGF levels in the PAS group (108 pg/ml, 38-679 pg/ml) was higher than that in the PP group (43 pg/ml, 12-111 pg/ml) (p < 0.0001 and p < 0.0001, respectively). The area under the ROC of the sFlt-1 levels, PLGF levels, and sFlt-1/PLGF ratio were 0.91, 0.90, and 0.99, respectively; the cut-off values were 18.9 ng/ml, 75.9 pg/ml, and 229.5, respectively. The concentration of sFlt-1 and sFlt-1/PLGF ratio were associated with the volume of blood loss (-.288*, -.301*). DISCUSSION: The concentrations of sFlt-1 and PLGF and ratio of plasma sFlt-1/PLGF may distinguish patients with placenta accreta from those with placenta previa.

PRG2 and AQPEP are misexpressed in fetal membranes in placenta previa and percreta†.

The obstetrical conditions placenta accreta spectrum (PAS) and placenta previa are a significant source of pregnancy-associated morbidity and mortality, yet the specific molecular and cellular underpinnings of these conditions are not known. In this study, we identified misregulated gene expression patterns in tissues from placenta previa and percreta (the most extreme form of PAS) compared with control cases. By comparing this gene set with existing placental single-cell and bulk RNA-Seq datasets, we show that the upregulated genes predominantly mark extravillous trophoblasts. We performed immunofluorescence on several candidate molecules and found that PRG2 and AQPEP protein levels are upregulated in both the fetal membranes and the placental disk in both conditions. While this increased AQPEP expression remains restricted to trophoblasts, PRG2 is mislocalized and is found throughout the fetal membranes. Using a larger patient cohort with a diverse set of gestationally aged-matched controls, we validated PRG2 as a marker for both previa and PAS and AQPEP as a marker for only previa in the fetal membranes. Our findings suggest that the extraembryonic tissues surrounding the conceptus, including both the fetal membranes and the placental disk, harbor a signature of previa and PAS that is characteristic of EVTs and that may reflect increased trophoblast invasiveness.

Maternal and Neonatal Complications in Patients With Diminished Ovarian Reserve in In-Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles.

Background: Diminished ovarian reserve (DOR) is one of the most intractable clinical issues in human reproduction and is reported to be associated with raised risk of recurrent pregnancy loss and aneuploid blastocysts. In this study, we aimed to explore whether DOR was also associated with maternal and neonatal complications in in-vitro fertilization/intracytoplasmic sperm injection cycles. Methods: A retrospective cohort study including women below 40 years of age who achieved singleton live birth after fresh embryo transfer in in-vitro fertilization/intracytoplasmic sperm injection cycles in a single center from January 2012 to June 2019 was conducted. Participants with DOR, defined as basal follicle-stimulating hormone (FSH) ≥ 10IU/L and antimullerian hormone (AMH) < 1.2ng/ml, were enrolled as the study group. The controls were 1:2 matched by age and body mass index with FSH < 10IU/L and AMH ≥ 1.2ng/ml. Maternal and neonatal complications were compared between the DOR group and the controls. Results: A total of 579 women, 193 in the DOR group and 386 matched as controls, were included in this study. Compared to controls, the incidence of hypertensive disorders of pregnancy was significantly increased in the DOR group (5.7% vs. 2.1%, P = 0.021). DOR patients also presented slightly higher incidences of preterm birth (10.9% vs. 7.5%, P = 0.174) and low birthweight (6.2% vs. 5.4%, P = 0.704) yet without statistical significances. The incidences of gestational diabetes mellitus and placenta previa were comparable between the two groups. Conclusion: Compared to women with normal ovarian reserve, women with diminished ovarian reserve might have elevated incidence of hypertensive disorders of pregnancy. Patients with diminished ovarian reserve might need more strict antenatal care.

Elevated immunoexpression of interferon-gamma in placenta tissue samples from pregnancies complicated with preeclampsia compared to the placenta previa.

AIM: The present study aimed to compare the immunohistochemical expression of interferon-gamma (IFN-γ) in placentas from pregnancies complicated with preeclampsia (PE) and placenta previa (PP) and normal healthy placentas. METHODS: Placentas were collected from cases of PE, PP and normal pregnancies as a control group (10 placentas in each group). All the deliveries were at full-term (37-42 weeks) by cesarean section and newborns were without any complications or diseases. Expression of IFN-γ in the placenta was determined using immunohistochemical methods and findings were compared. Statistical analysis was performed by Mann-Whitney and Kruskal-Wallis tests for comparing the mean values of IFN-γ expression in the placentas from PE, PP and control groups. Our results showed that the immunoexpression of IFN-γ in syncytiotrophoblast cells, extravillous trophoblast cells, vascular endothelium and basal plate of the placenta from PE group were more than control and PP groups (P < 0.05) and in PP group were more than the control group (P < 0.05). CONCLUSION: We concluded that the immunoexpression of IFN-γ was increased significantly in placenta tissue samples of the PE group compared to the PP group and normal pregnancies. It is proposed that IFN-γ has an important role in the different mechanisms of PE and PP progression.

The role of Zeb1 in the pathogenesis of morbidly adherent placenta.

Zinc finger E­box­binding homeobox 1 (Zeb1) is a promoter of epithelial­mesenchymal transformation, which may serve an important role in morbidly adherent placenta (MAP). In the present study, the protein expression levels of Zeb1 were examined in the placenta tissues of 60 patients, including 20 patients with placenta accreta (PA) and 20 patients with placenta previa without PA (UPA) and 20 patients in late pregnancy that delivered by cesarean section (normal). The expression levels of Zeb1, N­cadherin, vascular endothelial growth factor (VEGF), Tumor necrosis factor­related apoptosis­inducing ligand­receptor 2 (TRAIL­R2), and tumor necrosis factor­related apoptosis­inducing ligand­receptor 3 (TRAIL­R3) were higher in PA tissues compared with in normal control tissues. The expression levels of E­cadherin and TRAIL­R2 were decreased in PA tissues compared with in normal control tissues. These findings indicated that Zeb1 may serve an important role in placental attachment, thus promoting the development of dangerous PA. Overexpression of Zeb1 may upregulate the expression levels of N­cadherin, VEGF, TRAIL­R3, cyclin D1 and Bcl­2, and downregulate the expression levels of E­cadherin and TRAIL­R2. In addition, Zeb1 regulated the viability, apoptosis and migration of HTR­8/SV neo cells and human umbilical vein endothelial cells by regulating the Akt pathway. In conclusion, these findings indicated that Zeb1 may promote placental implantation by activating the Akt signaling pathway, thus providing a theoretical basis for investigating the causes of MAP.

Associations between metal concentrations in whole blood and placenta previa and placenta accreta: the Japan Environment and Children's Study (JECS).

BACKGROUND: Placenta previa and placenta accreta associate with high morbidity and mortality for both mothers and fetus. Metal exposure may have relationships with placenta previa and placenta accreta. This study analyzed the associations between maternal metal (cadmium [Cd], lead [Pb], mercury [Hg], selenium [Se], and manganese [Mn]) concentrations and placenta previa and placenta accreta. METHODS: We recruited 17,414 women with singleton pregnancies. Data from a self-administered questionnaire regarding the first trimester and medical records after delivery were analyzed. Maternal blood samples were collected to measure metal concentrations. The subjects were classified into four quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. RESULTS: The odds ratio for placenta previa was significantly higher among subjects with Q4 Cd than those with Q1 Cd. The odds ratio for placenta previa was significantly higher for subjects with Q2 Pb than those with Q1 Pb. CONCLUSION: Participants with placenta previa had higher Cd concentrations. However, this study was cross-sectional and lacked important information related to Cd concentration, such as detailed smoking habits and sources of Cd intake. In addition, the subjects in this study comprised ordinary pregnant Japanese women, and it was impossible to observe the relationship between a wide range of Cd exposure and placenta previa. Therefore, epidemiological and experimental studies are warranted to verify the relationship between Cd exposure and pregnancy abnormalities.

Expression of Cripto-1 in the placenta and its role in placenta accreta and placenta previa.

OBJECTIVES: This study Aims to explore the role of placental Cripto-1 in the incidence of an adherent placenta. MATERIAL AND METHODS: Ten pregnant women with placenta increta, 20 pregnant women with placenta previa and 30 women with normal pregnant were enrolled in this study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of Cripto-1 in the placenta while as the analysis of placental Cripto-1 was performed by Western blotting RESULTS: The placenta increta group showed higher levels of Cripto-1 in the center of the increta as compared to the non-implantation area. The level of placental Cripto-1 in the placenta increta was higher than that of the placenta accrete. The expression of placental Cripto-1 in the placenta increta and placenta previa groups was higher than that of control. CONCLUSIONS: Placental Cripto-1 is involved in the regulation of placental tissue invasion. Additionally, excessive placental growth or penetration into the myometrium are likely to be involved in the development of placenta increta.

Expression of ß-catenin in human trophoblast and its role in placenta accreta and placenta previa.

OBJECTIVES: To investigate the expression of ß-catenin in chorionic villi, and to explore its roles in placenta accreta and placenta previa. METHODS: We compared ß-catenin expression in the control group, placenta accreta group (lesion area and normal zones), and placenta previa group (placental central and placental edge zones) by immunohistochemistry, Western blotting, and RT-PCR techniques. RESULTS: Compared with the normal group, the placenta accreta group had a longer length of stay, greater bleeding volume, and lower newborn birth weight. Further, the expression of ß-catenin was lower in both placenta previa and placenta accreta groups than in the control group, as measured by immunohistochemistry. Compared with the control group, expression of ß-catenin was significantly lower in the placenta previa and placenta accreta groups by Western blotting and RT-PCR. Importantly, the level of placental ß-catenin was significantly different when compared between the lesion and normal zones of placenta. CONCLUSION: The expression of ß-catenin in placenta accreta might play an important role in the regulation of placental cell invasion; low expression of ß-catenin in placenta accreta might be responsible for excessive trophoblastic invasion.

Nestin is highly expressed in foetal spinal cord isolated from placenta previa patients and promotes inflammation by enhancing NF-κB activity.

PURPOSE: Nestin is expressed in various tissues of the embryo in patients with placenta previa, while the regulatory mechanism still unknown. MATERIALS AND METHODS: All participants terminated pregnancy. Among them, 75 patients with placenta previa were assigned to the case group and 80 healthy pregnant women with normal placenta were assigned to the control group. Expression of nestin and CDK5 in foetal spinal cord tissues was detected by Western blot and quantitative real-time RT-PCR methods. The enzyme-linked immunosorbent assay (ELISA) was used to determine the serum expression of some pro-inflammatory cytokines in placenta previa patients. The interaction between nestin and CDK5 was evaluated by immunoprecipitation and siRNA inhibition of nestin was performed to estimate its effect on NF-κB activity in foetal spinal cord tissues. RESULTS: Along with increased expression of nestin and CDK5 in foetal spinal cord tissues in the case group, IL-1ß, IL-6, TNF-α and IFN-γ were increased in the serum of placenta previa patients. siRNA inhibition analysis indicated that nestin interacted with CDK5 and regulated NF-κB activity in foetal spinal cord tissues. CONCLUSIONS: Nestin is highly expressed and the interaction between nestin and CDK5 might lead to the progress of placenta previa through its regulation on NF-κB.

Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta.

Differentiation of first trimester human placental cytotrophoblast (CTB) from an anchorage-dependent epithelial phenotype into the mesenchymal-like invasive extravillous trophoblast (EVT) is crucial in the development of the maternal-fetal interface. We showed previously that differentiation of first trimester CTB to EVT involves an epithelial-mesenchymal transition (EMT). Here we compare the epithelial-mesenchymal characteristics of CTB and EVT derived from normal third trimester placenta or placenta previa versus abnormally invasive placenta (AIP). CTB and EVT were isolated from normal term placenta or placenta previa following Caesarean section and EVT from AIP following Caesarean hysterectomy. Cell identity was validated by measurement of cytokeratin-7 and HLA-G. Comparing normal term CTB with EVT from normal term placenta or placenta previa for differential expression analysis of genes associated with the EMT showed changes in >70% of the genes probed. While demonstrating a mesenchymal phenotype relative to CTB, many of the gene expression changes in third trimester EVT were reduced relative to the first trimester EVT. We suggest that third trimester EVT are in a more constrained, metastable state compared to first trimester equivalents. By contrast, EVT from AIP demonstrate characteristics that are more mesenchymal than normal third trimester EVT, placing them closer to first trimester EVT on the EMT spectrum, consistent with a more invasive phenotype.

Expression of nestin in embryonic tissues and its effects on clinicopathological characteristics of patients with placenta previa.

In this study, we examined expression of nestin in the spinal cord, lung, kidney, stomach, colon, and intestine tissues at different stages of embryos in patients with placenta previa. Fetuses of 75 patients with placenta previa were assigned to case group and 80 fetuses from healthy pregnant women with normal placenta who voluntarily terminated pregnancy to control group. Clinical data of pregnant women were collected at the time of admission. Blood from elbow vein was collected to determine expression of serum nestin. Tissues from spinal cord, lung, kidney, stomach, colon, and intestine in 3-7 months fetuses of the two groups were extracted. Expression of nestin in tissues was detected by immunohistochemistry, Western blotting and RT-qPCR. The mRNA expression of nestin in the case group was increased. Nestin expression was correlated with the gestational age, age of foetus, and type of placenta previa in patients with placenta previa. Positive nestin expression was detected in the spinal cord, lung, kidney, stomach, intestine, and colon tissues in normal and placenta previa embryo at Stage I. The positive cell density and nestin expression decreased at Stage II, and further decreased at Stage III. The case group had higher nestin mRNA and protein levels throughout human fetal development. Findings of this study suggested that, nestin, as a specific marker of neural precursor cells, was expressed in various tissues of the embryo in patients with placenta previa and nestin expression was lower with increased maturation of the embryo.

Increased expression of high mobility group box protein 1 and vascular endothelial growth factor in placenta previa.

Placenta previa is often associated with preterm delivery, reduced birth weight, a higher frequency of placental accreta and postpartum haemorrhage, and increased likelihood of blood transfusion. The present study aimed to examine the expression of high mobility group box protein 1 (HMGB1) in the placenta of women with or without placenta previa. The study group consisted of placental tissues obtained from women with or without placenta previa. The expression levels of HMGB1 and vascular endothelial growth factor (VEGF) were evaluated in the placental tissues using reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemistry. The mRNA expression levels of HMGB1 and VEGF were significantly increased in the placenta previa group compared with in the normal group. In addition, the placenta previa group exhibited increased HMGB1 and VEGF staining in vascular endothelial cells and trophoblasts. There were no significant differences in the expression of HMGB1 or VEGF between groups with or without placenta accreta or postpartum haemorrhage. The present study hypothesised that the increased expression of HMGB1 in the placenta may be associated with the pathogenesis of placenta previa by regulating the expression of the proangiogenic factor VEGF.

Prediction of spontaneous preterm birth using fetal fibronectin in women with a low-lying placenta.

OBJECTIVE: To determine the effect of a low-lying placenta on the concentration of quantitative fetal fibronectin (qfFN) in the cervicovaginal fluid (CVF), and predictive accuracy for spontaneous preterm birth in asymptomatic high-risk women (18 + 0-24 + 0 weeks gestation). METHODS: Median concentrations of qfFN were compared in women who had a low-lying placenta, covering the cervical os (n = 61) to matched controls (n= 61) without a low-lying placenta. Proportions of women with raised qfFN concentrations (>10 ng/ml), and false positive and negative rates (FPR and FNR) for spontaneous preterm delivery were also compared. RESULTS: The median concentration of qfFN in women with low-lying placenta was 5.0 ng/mL, compared with 6.0 ng/mL in controls. Proportion of women with raised levels (>10 ng/mL), positive levels (>50 ng/mL) and very high levels (>200 ng/mL) were similar in both groups (62.3% versus 59.0%, 16.3% versus 22.0% and 6.5% versus 4.9%, p > 0.05 for all thresholds). The FPR and FNR rate for delivery before 34 and 37 weeks were also comparable (FPR 90.0% versus 85.7% and 80.0% versus 78.6%; FNR 5.8% versus 4.3% and 9.8% versus 8.5%). CONCLUSIONS: CVF qfFN concentrations in asymptomatic high-risk women are not affected by the presence of a low-lying placenta.

Decreased placental and maternal serum TRAIL-R2 levels are associated with placenta accreta.

OBJECTIVES: TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) is produced both by decidual and trophoblast cells during pregnancy and known to participate in apoptosis. In this study, we aimed to determine and to compare maternal serum and placental TRAIL-R2 levels in patients with placenta accreta, non-adherent placenta previa and in healthy pregnancies. We also aimed to analyze the association of placenta accreta with the occurrence of previous C-sections. STUDY DESIGN: A total of 82 pregnant women were enrolled in this case-control study (27 placenta accreta patients, 26 non-adherent placenta previa patients and 29 age-, and BMI-matched healthy, uncomplicated pregnant controls). TRAIL-R2 levels were studied in both maternal serum and placental tissue homogenates. Determining the best predictor(s) which discriminate placenta accreta was analyzed by multiple logistic regression analyses. Adjusted odds ratios and 95% confidence intervals were also calculated. RESULTS: Both placental and serum TRAIL-R2 levels were significantly lower in placenta accreta group (median 34.82 pg/mg and 19.85 pg/mL, respectively) when compared with both non-adherent placenta previa (median 39.24 pg/mg and 25.99 pg/mL, respectively) and the control groups (median 41.62 pg/mg and 25.87 pg/mL, respectively) (p < 0.05). Placental TRAIL-R2 levels and previous cesarean section were found to be significantly associated with placenta accreta (OR: 0.934 95% CI 0.883-0.987, p = 0.016 and OR:7.725 95% CI: 2.717-21.965, p < 0.001, respectively). Placental and serum TRAIL-R2 levels were positively correlated. CONCLUSION: Decreased levels of placental TRAIL-R2 and previous history of cesarean section were found to be significantly associated with placenta accreta, suggesting a possible role of apoptosis in abnormal trophoblast invasion.

[Determination of glutamic acid in biological material by capillary electrophoresis].

The conditions for the identification and determination of Glutamic acid by capillary zone electrophoresis without their preliminary derivatization have been optimized. The effect of concentration of buffer electrolyte and pH on determination of Glutamic acid has been investigated. It is shown that the 5 Mm borate buffer concentration and a pH 9.15 are optimal. Quantitative determination of glutamic acid has been carried out using a linear dependence between the concentration of the analyte and the area of the peak. The accuracy and reproducibility of the determination are confirmed by the method "introduced - found". Glutamic acid has been determined in the placenta homogenate. The duration of analysis doesn't exceed 30 minutes. The results showed a decrease in the level of glutamic acid in cases of pregnancy complicated by placental insufficiency compared with the physiological, and this fact allows to consider the level of glutamic acid as a possible marker of complicated pregnancy.

Ki-67 proliferation index in patients with placenta previa percreta in the third trimester.

AIM: The purpose of this study was to investigate proliferative capacity of placenta previa percreta in the third trimester via evaluating Ki-67 proliferating index. METHODS: The paraffin blocks of placental tissues, which were obtained from the patients who underwent hysterectomy for placenta previa percreta (n = 12, gestational age > 28 weeks), from legal abortions (n = 12, gestational age < 10 weeks), and of cesarean deliveries with the indication of previous cesarean section, without any complication (n = 12, gestational age > 38 weeks), between January 2011 and April 2013, were included into the study. The paraffin blocks of the patients were stained with Ki-67 (proliferating cell marker) immunohistochemically, and Ki-67 proliferation index levels were calculated. RESULTS: Ki-67 proliferation index levels were higher in patients with legal abortions than patients with placenta percreta or noncomplicated cesarean delivery group. However, any statistically significant difference was not detected between the percreta and noncomplicated groups (p > 0.05). CONCLUSION: The tissue samples of the patients with placenta previa percreta exhibited low proliferative capacity similar to the samples of normal placentation group.

A survey of zeb1, twist and claudin 1 and 4 expression during placental development and disease.

We investigated zeb1, twist and claudins 1 and 4 in normal and diseased placental tissues. Eighty cases of placental tissues from all three trimesters and from different diseases were studied immunohistochemically to determine the expression of zeb1, twist and claudins 1 and 4. Zeb1 was more strongly expressed in endothelial and mesenchymal cells of the villous structures during the last two trimesters, suggesting that it plays a role in the development of placental blood vessels. In contrast, twist was more strongly expressed in the trophoblastic cells during these trimesters. The endothelial and stromal expression of zeb1 and the epithelial expression of twist were disturbed in those placentas with chromosomal aberrations. Claudin 4 was strongly expressed in trophoblastic cells during all trimesters. Its expression was especially strong in molar disease, suggesting that it could participate in trophoblastic aggregation and disturbed attachment of trophoblastic cells in the expanded villi. Claudin 4 expression was also increased in the placentas of diabetic mothers and in toxaemia. Claudin 1 did not show any specific disease associations. The study implicates that twist and zeb1 are involved in placental maturation, whereas claudin 4 appears to be connected with placental diseases such as diabetes, toxaemia or molar disease.