Placental Tissues Of Pregnant Women Research Articles

Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway.

Pre-eclampsia (PE) is a severe pregnancy complication characterized by impaired trophoblast invasion and spiral artery remodeling and can have serious consequences for both mother and child. Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) is involved in numerous tumor-related biological processes. However, the biological action and underlying mechanisms of PPP1R3G in PE progression remain unclear. We used western blotting and immunohistochemistry to investigate PPP1R3G expression in gestational age-matched pre-eclamptic and normal placental tissues. After lentivirus transfection, wound-healing, Transwell, cell-counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and TdT mediateddUTP Nick End Labeling (TUNEL) assays were used to assess trophoblast migration, invasion, proliferation, and apoptosis, respectively. The relative expression levels of PPP1R3G and the proteins involved in the Akt signaling pathway were determined using western blotting. The results showed that PPP1R3G levels were significantly lower in the placental tissues and GSE74341 microarray of the PE group than those of the healthy control group. We also found that neonatal weight and Apgar score were lower at birth, and peak systolic blood pressure and diastolic blood pressure were higher in the PE group than in the non-PE group. In addition, PPP1R3G knockdown decreased p-Akt/Akt expression and inhibited migration, invasion, and proliferation in HTR-8/SVneo trophoblasts but had no discernible effect on cell apoptosis. Furthermore, PPP1R3G positively regulated matrix metallopeptidase 9 (MMP-9), which was downregulated in placental tissues of pregnant women with PE. These results provided the first evidence that the reduced levels of PPP1R3G might contribute to PE by suppressing the invasion and migration of trophoblasts and targeting the Akt/MMP-9 signaling pathway.

Levels of PFAS concentrations in the placenta and pregnancy complications

BackgroundRecent research has raised concerns about the potential health effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure, particularly during critical periods of development such as pregnancy. In this study, we sought to investigate the presence and potential impacts of PFAS in the placenta. MethodsWe measured 13 PFAS compounds in placental tissue samples among 50 women who gave birth at a tertiary medical center in southern Israel. The sample comprised of 10 women with pregnancy-related complications (preterm birth, preeclampsia, gestational diabetes or small-for-gestational age) and 40 women without complications individually matched to cases by age. ResultsFor five (5) out of 13 PFAS compounds (Perfluorooctane Sulfonate (PFOS), perfluorooctanoic acid (PFOA), Perfluorohexanesulphonic acid (PFHxS), Perfluorononanoic acid (PFNA), Perfluorodecanoic acid (PFDA)) median concentrations were lower or comparable to placental measurements in different international populations. Geometric mean was estimated at 0.09 ng/g (90%CI:0.07;0.10) for PFOA, 0.05 ng/g for PFNA (90%CI:0.04;0.07), 0.03 ng/g for PFDA (90%CI:0.01;0.03), 0.06 ng/g for PFHxS (90%CI:0.05;0.07), 0.23 ng/g for PFOS linear measurement (90%CI:0.20;0.26) and 0.25 ng/g (90%CI:0.22;0.30) for PFOS summed concentrations that included non-linear isomers. Composite outcome of pregnancy-related complications was associated with elevated PFOA placental concentrations at an odds ratio (OR)= 1.82 (90%CI:1.06;3.13) for an increase of one quintile of PFOA value and adjusted to maternal gravidity in a conditional logistic regression. ConclusionThis pilot study indicates a widespread exposure to multiple PFAS compounds in placental tissue of pregnant women in Israel. These findings warrant further validation through comprehensive national human biomonitoring initiatives.

Assessment of Tissue Expression of the Oxytocin-Vasopressin Pathway in the Placenta of Women with a First-Episode Psychosis during Pregnancy.

Psychosis refers to a mental health condition characterized by a loss of touch with reality, comprising delusions, hallucinations, disorganized thought, disorganized behavior, catatonia, and negative symptoms. A first-episode psychosis (FEP) is a rare condition that can trigger adverse outcomes both for the mother and newborn. Previously, we demonstrated the existence of histopathological changes in the placenta of pregnant women who suffer an FEP in pregnancy. Altered levels of oxytocin (OXT) and vasopressin (AVP) have been detected in patients who manifested an FEP, whereas abnormal placental expression of these hormones and their receptors (OXTR and AVPR1A) has been proven in different obstetric complications. However, the precise role and expression of these components in the placenta of women after an FEP have not been studied yet. Thus, the purpose of the present study was to analyze the gene and protein expression, using RT-qPCR and immunohistochemistry (IHC), of OXT, OXTR, AVP, and AVPR1a in the placental tissue of pregnant women after an FEP in comparison to pregnant women without any health complication (HC-PW). Our results showed increased gene and protein expression of OXT, AVP, OXTR, and AVPR1A in the placental tissue of pregnant women who suffer an FEP. Therefore, our study suggests that an FEP during pregnancy may be associated with an abnormal paracrine/endocrine activity of the placenta, which can negatively affect the maternofetal wellbeing. Nevertheless, additional research is required to validate our findings and ascertain any potential implications of the observed alterations.

SWATH proteomics analysis of placental tissue with intrahepatic cholestasis of pregnancy

IntroductionIntrahepatic cholestasis of pregnancy (ICP) usually occurs in the second and third trimesters. The disease's etiology and diagnostic criteria are currently unknown. Based on a sequence window to obtain all theoretical fragment ions (SWATH) proteomic approach, this study sought to identify potential proteins in placental tissue that may be involved in the pathogenesis of ICP and adverse fetal pregnancy outcomes. MethodsThe postpartum placental tissue of pregnant women with ICP were chosen as the case group (ICP group) (subdivided into mild ICP group (MICP group) and severe ICP group (SICP group)), and healthy pregnant women were chosen as the control group (CTR). The hematoxylin-eosin (HE) staining was used to observe the histologic changes of placenta. The SWATH analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS) was used to screen the differentially expressed proteins (DEPs) in ICP and CTR groups, and bioinformatics analysis was used to find out the biological process of these differential proteins. ResultsProteomic studies showed there were 126 DEPs from pregnant women with ICP and healthy pregnant women. Most of the identified proteins were functionally related to humoral immune response, cell response to lipopolysaccharide, antioxidant activity and heme metabolism. A subsequent examination of placentas from patients with mild and severe ICP revealed 48 proteins that were differentially expressed. Through death domain receptors and fibrinogen complexes, these DEPs primarily regulate extrinsic apoptotic signaling pathways, blood coagulation, and fibrin clot formation. The differential expressions of HBD, HPX, PDE3A, and PRG4 were down-regulated by Western blot analysis, which was consistent with proteomics. DiscussionThis preliminary study helps us to understand the changes in the placental proteome of ICP patients, and provides new insights into the pathophysiology of ICP.

Long noncoding RNA maternally expressed gene 3 improves trophoblast dysfunction and inflammation in preeclampsia through the Wnt/β-Catenin/nod-like receptor pyrin domain-containing 3 axis.

Inadequate trophoblastic infiltration and resulting placental hypoxia and inflammation comprise the core pathological basis of preeclampsia (PE). Maternally expressed gene 3 (MEG3) is known to be involved in the pathogenesis of preeclampsia by inhibiting the migration and invasion of trophoblasts and promoting their apoptosis. Nevertheless, the specific underlying downstream molecular mechanism of MEG3 is less well characterized. In this study, we detected lower expression levels of MEG3 and β-Catenin and higher expression of nod-like receptor pyrin domain-containing 3 (NLRP3) in placental tissues of pregnant women with severe preeclampsia (sPE) than in normal pregnancies. Elevated serum levels of IL-1β and TNF-α were also observed in the sPE group. Then, we established a hypoxia/reoxygenation (H/R) model to mimic preeclampsia. Similar results with sPE group were found in the H/R group compared with the control group. In addition, suppressive trophoblast proliferation, migration and invasion and increases in the apoptotic rate and inflammation were also detected in the H/R group. Notably, overexpressing MEG3 markedly improved trophoblast dysfunction and inflammation caused by H/R. However, the effects of MEG3 on trophoblasts, whether upregulated or downregulated, can be reversed by DKK-1 (Wnt/β-Catenin inhibitor) and MCC950 (NLRP3 inhibitor). The current study revealed that MEG3 regulates trophoblast function and inflammation through the Wnt/β-Catenin/NLRP3 axis and provided new insights into the pathogenesis of preeclampsia.

How the nitric oxide and antioxidant enzymes work in the placental tissues of pregnant women with COVID 19 disease?

Objective: The aim of this study to examine the oxidative stress parameters in placental tissues and blood plasmas of pregnant women.
 Materials and Methods: The biochemical parameters were examined in 37 pregnant women with covid disease, 37 pregnant women who had covid, and 37 healthy pregnant women. The amounts of lipid peroxidation (LPO), glutathione (GSH), nitric oxide (NOx) and catalase (CAT), superoxide dismutase (SOD) enzyme activities were measured in each tissue and blood plasma.
 Results:The LPO levels increased in the pregnant woman who has had covid 19 compared with healthy pregnant. Likewise, the LPO levels increased in pregnant women who were negative at the time of delivery. While the amount of glutathione was high in healthy placental tissues, it was found to be quite low in covid 19 positive tissues. While the enzyme activities of SOD and NOx are quite high in placental tissues of healthy pregnant women, they are significantly low in covid positive and negative pregnant tissues. While the CAT enzymes activities, another antioxidant enzyme, was at a very low level in healthy placental tissues compared to SOD enzyme, it was significantly increased in positive pregnant placental tissues.
 Conclusion: The antioxidant enzyme activities and amounts show significant differences between groups in placental tissues. The changes in enzyme rates in placental tissues are proportional to blood plasma results.

Expression and role of miR-146a and SMAD4 in placental tissue of pregnant women with preeclampsia.

To investigate the expression of miR-146a in severe preeclampsia (PE) and its effect on trophoblast cell proliferation, invasion and apoptosis, as well as its relationship with SMAD4. Participants were divided into the severe PE group (n=30) and the normal group (n=30). The expression of miR-146a and SMAD4 in placenta tissue was detected by immunohistochemistry, qRT-PCR, and western blot. Trophoblast cell lines HTR-8/SVneo were cultured to detect the expression of miR-146a under the Cobalt chloride (CoCl2 )-simulated hypoxia. The effects of miR-146a transfection on cell proliferation, invasion, apoptosis, and SMAD4 expression were analyzed. Compared with the normal group, miR-146a expression was decreased and the protein and mRNA levels of SMAD4 were increased in placenta tissues of the severe PE group. Our in vitro experiments showed that the expression of miR-146a decreased after CoCl2 treatment. Silencing miR-146a caused increased expression of SMAD4 and decreased expression of VEGF. After transfection with miR-146a inhibitor, compared with the NC group, the invasion and proliferation of HTR-8/Svneo cells were decreased, while the apoptosis was enhanced. The expression of miR-146a decreased in severe PE and was negatively correlated with SMAD4 expression. The expression of miR-146a was inhibited under hypoxia, and the low expression of miR-146a affected the proliferation, invasion, and apoptosis of trophoblast cells.

DJ-1 upregulates the Nrf2/GPX4 signal pathway to inhibit trophoblast ferroptosis in the pathogenesis of preeclampsia

Ferroptosis is a newly discovered mode of cell death that involves disorders in iron metabolism and the accumulation of reactive oxygen species (ROS) in the plasma membrane. Preeclampsia (PE) is a gestational idiopathic disease that is characterized by hypertension and albuminuria, begins after 20 weeks of pregnancy. DJ-1 is a prerequisite for activating and stabilizing Nrf2 to allow translocation to the nucleus to carry out further functions. Detecting the expression levels of DJ-1, the Nrf2/GPX4 signaling pathway and ferroptosis markers in placental tissues of pregnant women with and without PE. Analyzing the effects of the ferroptosis inducer (RSL3) and the inhibitor (Fer-1) on the mortality rate of BeWo cells and DJ-1+/+, DJ-1−/− BeWo cells. Ferroptosis markers (MDA concentration and morphology of trophoblast cells) and DJ-1 and its downstream the Nrf2/GPX4 signaling pathway increased significantly in PE pathological state. The expression levels of DJ-1 protein in the control group and the PE group were positively correlated with the expression levels of Nrf2/GPX4 signaling pathway protein, and negatively correlated with the MDA concentration. BeWo cells were sensitive to the ferroptosis inducer (RSL3) and the inhibitor (Fer-1). The high expression levels of DJ-1 in BeWo cells can resist ferroptosis by regulating the Nrf2/GPX4 signaling pathway. Ferroptosis is involved in the pathogenesis of PE. DJ-1 can mediate the trophoblast cells ferroptosis and play a protective role in the pathogenesis of preeclampsia by regulating the Nrf2/GPX4 signaling pathway.

Antimicrobial Resistance Pattern in E. coli Isolated from Placental Tissues of Pregnant Women in Low-Socioeconomic Setting of Pakistan.

Infections during pregnancy can culminate in adverse pregnancy outcomes, including preterm birth (PTB). Pakistan is among the top ten nations with high PTB-associated neonatal mortality rates, where access to prenatal as well as neonatal care is only afforded by the privileged few. Societal stigma further discourages women seeking healthcare for minor infections. Microbial pathogens associated with genitourinary infections can lead to gestational complications culminating in earlier onset of labor. In this study, association of Escherichia coli (E. coli) with PTB in Pakistani women of low-socioeconomic status is examined. 57 paired vaginal swabs and placenta samples from mothers with full term and preterm deliveries were collected and processed for isolation and molecular characterization of extraintestinal pathogenic E. coli (ExPEC). ExPEC isolated from vaginal swabs and placenta showed phylotype B2 being most prevalent (Vagina n = 3 (9), 33%) (Placenta n = 4 (12), 33%) in preterm cases followed by phylotype B1 (Vagina n = 2 (9), 22%) (Placenta n = 3 (12), 25%) and untypeable strains. Antibiotic susceptibility profiling showed a large percentage of resistant isolates to multiple antibiotics, including carbapenem and included extended-spectrum beta-lactamase (ESBL) producers. Our study is the first to report different phylotypes of E. coli from placental tissues in preterm deliveries which may be a cause for concern for maternal and neonatal health. ExPEC from vaginal swabs and placental of females delivering preterm shows the pathogenic phylotype B2 dominance with a large percentage of isolates resistant to multiple antibiotics, including carbapenem and included ESBL producers. The placental isolates may indicate ascending infection from vagina or urinary tract which may lead to preterm birth.

Overexpression of glycolysis markers in placental tissue of pregnant women with chronic venous disease: a histological study.

Chronic Venous Disease (CVD) refers to a wide variety of venous disorders being the varicose veins its most common manifestation. It is well-established the link between pregnancy and the risk of suffering CVD, due to hormonal or haematological factors, especially during the third trimester. In the same manner, previous studies have demonstrated the detrimental effect of this condition in the placental tissue of pregnant women, including in the normal physiology and the metabolomic profile of this organ. In this context, the aim of this study was to evaluate the glucose homeostasis in the placental tissue of women presenting CVD. Through immunohistochemistry, we studied the protein expression of the glucose transporter 1 (GLUT-1), Phosphoglycerate kinase 1 (PGK1), aldolase (ALD), Glyceraldehyde-3-phosphate dehydrogenase (GA3PDH) and lactate dehydrogenase (LDH). Our results have reported a significative increase in the expression of GLUT-1, PGK1, ALD, GA3PDH and the isoenzyme LDHA in placentas of women with CVD. This work has proven for the first-time an altered glucose metabolism in the placental tissue of women affected by CVD, what may aid to understand the pathophysiological mechanisms of this condition in more distant organs such as placenta. Furthermore, our research also supports the basis for further studies in the metabolic phenotyping of the human placenta due to CVD, which may be considered during the late pregnancy in these women.

Ambient Black Carbon Particles Reach the Fetal Circulation

BACKGROUND AND AIM: Mothers’ exposure to ambient air pollution, including black carbon (BC), during pregnancy has been associated with several adverse birth outcomes. Although the presence of ambient combustion-related particulates was recently shown in the placental tissue of pregnant women, proof of placental translocation to the fetal circulation in a real-life human context is still lacking. Here, we screened human umbilical cord blood for the presence of BC as part of the combustion-derived particulate matter. METHODS: Cord blood BC load was determined in the framework of the ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort study. We exploited the non-incandescence related white-light generation by carbonaceous particles following femtosecond pulsed illumination to screen whole cord blood samples from 60 newborns for the presence of BC particles in a biocompatible and label-free manner. RESULTS:BC is identified in all screened blood samples, with an average (SD) particle count of 0.48 x 10⁵ (0.29 x 10⁵), 1.02 x 10⁵ (0.76 x 10⁵) and 2.87 x 10⁵ (2.12 x 10⁵) particles per mL cord blood for low (n=20), intermediate (n=20) and high (n=20) exposed mother-newborn pairs, respectively. Furthermore, the cord blood BC load is positively associated with the mothers’ residential BC exposure during pregnancy (n=60; r=0.72; p0.0001). Moreover, the carbonaceous nature of these particulates was confirmed. CONCLUSIONS:Identification of BC particles in the fetal circulation shows that ambient particulates can be transported towards the fetus and represents a plausible explanation for the observed detrimental health effects from early life onwards. KEYWORDS: Air pollution, In utero exposure, maternal-fetal transfer, black carbon

Ultrasound Parameters of Umbilical Artery Blood Flow Are Associated with Amniotic Fluid and Umbilical Artery Concentrations of Erythropoietin and Oxidative Stress Injury

Intrauterine hypoxia is the most frequent adverse intrauterine condition that occurs under a variety of circumstances including preeclampsia, placental insufficiency, high-altitude pregnancy, and any inflammatory condition during pregnancy resulting from gestational diabetes or even maternal obesity. However, early diagnosis of intrauterine hypoxia is still a challenge. In this study, we comparatively analyzed the systolic to diastolic ratio (S/D), resistant index (RI), and pulse index (PI) of the umbilical artery (UmA) and middle cerebral artery (MCA) blood flows obtained from 46 pregnant women with intrauterine hypoxia and 80 normal pregnant women at 28-31, 32-36, and 37-41 gestational weeks. Results found that the S/D, RI, and PI of UmA and MCA blood flows at 28-31, 32-36, and 37-41 gestational weeks were all increased in hypoxic fetuses than in normal fetuses ( P < 0.05 ). The malondialdehyde (MDA) level was elevated but superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities were reduced in the UmA blood of pregnant women with intrauterine hypoxia compared with normal pregnant women ( P < 0.05 ). It was found that the NADPH oxidase 2 (Nox2) and NADPH oxidase 4 (Nox4) activities were increased in the UmA blood of pregnant women with intrauterine hypoxia compared with normal pregnant women ( P < 0.05 ). Results of ELISA methods showed that the expression level of survivin was lower but the expression levels of caspase-3, caspase-6, and caspase-9 were higher in the placental tissues of pregnant women with intrauterine hypoxia than those in normal pregnant women ( P < 0.05 ). The concentrations of erythropoietin in the amniotic fluid and UmA blood were increased in pregnant women with intrauterine hypoxia compared with normal pregnant women ( P < 0.05 ). The Spearman correlation analysis showed that the S/D, RI, and PI of UmA blood flow at 37-41 gestational weeks were positively correlated with the levels of Nox2, Nox4, and MAD and the UmA concentration of erythropoietin but negatively correlated with the activities of SOD, GSH-Px, and CAT ( P < 0.05 ). In summary, the study indicates that ultrasound parameters of the UmA blood flow including S/D, RI, and PI could serve as predictors of intrauterine hypoxia.

O-GlcNAcylation inHyperglycemic Pregnancies: Impact on Placental Function.

The dynamic cycling of N-acetylglucosamine, termed as O-GlcNAcylation, is a post-translational modification of proteins and is involved in the regulation of fundamental cellular processes. It is controlled by two essential enzymes, O-GlcNAc transferase and O-GlcNAcase. O-GlcNAcylation serves as a modulator in placental tissue; furthermore, increased levels of protein O-GlcNAcylation have been observed in women with hyperglycemia during pregnancy, which may affect the short-and long-term development of offspring. In this review, we focus on the impact of O-GlcNAcylation on placental functions in hyperglycemia-associated pregnancies. We discuss the following topics: effect of O-GlcNAcylation on placental development and its association with hyperglycemia; maternal-fetal nutrition transport, particularly glucose transport, via the mammalian target of rapamycin and AMP-activated protein kinase pathways; and the two-sided regulatory effect of O-GlcNAcylation on inflammation. As O-GlcNAcylation in the placental tissues of pregnant women with hyperglycemia influences near- and long-term development of offspring, research in this field has significant therapeutic relevance.

P57: Tumor necrosis factor alpha in placental tissue of pregnant women with preeclampsia: Immunohistochemical analysis

P57: Tumor necrosis factor alpha in placental tissue of pregnant women with preeclampsia: Immunohistochemical analysis

Dynamic Changes of Fetal-Derived Hypermethylated RASSF1A and Septin 9 Sequences in Maternal Plasma.

DNA methylation has a tissue-specific feature, and placenta has distinct methylation patterns from peripheral blood cells. Although fetal/placental-derived cell free DNA (cfDNA) in the maternal blood has been reported in recent decades, systematic exploration of dynamic changes of the placental epigenetic signatures across gestation is lacking. The primary goal of this study was to characterize prenatal and postnatal methylation levels of placental-sourced RASSF1A and Septin 9 sequences in maternal plasma. Here, we used a quantitative methylation-sensitive PCR (qMS-PCR) assay to check the methylation status of RASSF1A and Septin 9 in placental tissues of pregnant women and plasma samples from non-pregnant individuals. Then, we examined the methylation levels of the two targets in maternal plasma from expectant women at different gestational ages and postdelivery. Hypermethylated RASSF1A and Septin 9 were identified in placental samples but undetectable in peripheral blood of healthy non-pregnant women. Further, hypermethylated RASSF1A sequence was found in all three trimesters of pregnancy except for early gestation (8weeks). Moreover, methylation scores of the two targets increased as pregnancy progressed. In addition, hypermethylated RASSF1A sequence was detectable in maternal plasma from 12h (one case) to 24h postdelivery (three cases) in 18 pregnant women. Our data on the variation of fetal-sourced methylated RASSF1A levels in maternal plasma in relation to gestational age provide a useful basis for improving the reliability of the methylation assay for non-invasive prenatal diagnosis (NIPD) in clinical practice.

Особенности васкулогенеза и ангиогенеза в плаценте на фоне химиотерапии

Aim: to study placental vasculogenesis and angiogenesis in women receiving chemotherapy. Patients and Methods: placental structure was examined in 57 pregnant women aged 22–38 years who were subdivided into 3 groups, i.e., women with malignancies receiving or not receiving chemotherapy and healthy controls. The slices of the central part of placentas collected after childbirth were examined. Immunohistochemistry (IHC) was performed after standard histology. IHC intensity was assessed for CD31 and CD34. In addition to IHC intensity, the number of positive cells per field of view was calculated for VEGF, VEGFR1, and VEGFR2. Mean counts of positive cells separately for epithelial and stromal cells were calculated for eNOS. Results: in the control group, the maturity of the placental villous tree matched the gestational age. Meanwhile, in 100% of pregnant women with malignancies receiving chemotherapy and in 46.8% of pregnant women with malignancies not receiving chemotherapy, the maturity of the placental villous tree was 2–4 weeks behind the gestational age. IHC revealed no significant differences in the placental concentrations of CD31, CD39, eNOS, VEGF, VEGFR1, and VEGFR2 between women with malignancies not receiving chemotherapy and the controls. In women receiving chemotherapy, IHC intensity and the number of positive cells were twice as high as in the control group. The activity of VEGFR1 and VEGFR2 was 11 times higher and 1.4 times higher, respectively, than in the control group. The mean number of cells expressing VEGFR1 and VEGFR2 per field of view increased by 1.5 times and 1.7 times, respectively. In addition, 1.6-fold reduction in CD31 level and 1.3-fold reduction in CD34 level as well as 1.4-fold increase in epithelial еNOS level and 1.3-fold increase in stromal eNOS level were revealed. Conclusions: our findings on IHC distribution of the expression of VEGF and its recep-tors in the placental tissue of pregnant women undergoing cytostatic chemotherapy in part illus-trate the processes of the compensation and impaired functioning of the mother-placentafetus system in pre-placental hypoxia. KEYWORDS: angiogenesis, vasculogenesis, vascular growth factor, chemotherapy, hypoxia, placental insufficiency. FOR CITATION: Yu.E. Dobrokhotova, Borovkova E.I., Arutyunyan A.M. et al. Placental vasculogenesis and angiogenesis in women undergoing chemotherapy. Russian Journal of Woman and Child Health. 2021;4(1):23–30. DOI: 10.32364/2618-8430-2021-4-1-23-30.

Downregulation of IGF2 expression in third trimester placental tissues from Zika virus infected women in Brazil

ObjectivesScreening for genes differentially expressed in placental tissues, aiming to identify transcriptional signatures that may be involved in ZIKV congenital pathogenesis. MethodsTranscriptome data from placental tissues of pregnant women naturally infected with Zika virus during the third trimester were compared to those from women who tested negative for Zika infection. The findings were validated using both a cell culture model and an immunohistochemistry/morphological analysis of naturally infected placental tissues. ResultsTranscriptome analysis revealed that Zika virus infection induces downregulation of insulin-like growth factor II (IGF2) gene, an essential factor for fetal development. The Caco-2 cell culture model that constitutively expresses IGF2 was used for the transcriptome validation. Asiatic and African Zika virus strains infection caused downregulated IGF2 gene expression in Caco-2 cells, whereas other flaviviruses, such as dengue serotype 1, West Nile and wild-type yellow fever viruses, had no effect on this gene expression. Immunohistochemical assays on decidual tissues corroborated our transcriptome analysis, showing that IGF2 is reduced in the decidua of Zika virus-infected women. ConclusionsOur results draw attention to IGF2 modulation in uterine tissues, and this finding is expected to support future studies on strategies to ameliorate the harmful effects of Zika virus infection during pregnancy.

MiR-135a-5p promotes the migration and invasion of trophoblast cells in preeclampsia by targeting β-TrCP

BackgroundMiR-135a-5p is an important regulator of cell migration and invasion in several diseases. However, the biological functions and mechanisms of miR-135a-5p in women with preeclampsia (PE) remain unclear. MethodsThe levels of miR-135a-5p and beta-transducin repeat containing E3 ubiquitin protein ligase (β-TrCP) expression in samples of placenta tissue from PE patients and healthy control subjects were determined by quantitative real-time PCR. The effects of miR-135a-5p and β-TrCP on cell migration, invasion, and epithelial-mesenchymal transition (EMT) in two trophoblast cell lines (HTR-8/SVneo and TEV-1) were examined using wound healing, Transwell, and western blot assays, respectively. A luciferase reporter assay was performed to confirm the association between miR-135a-5p and β-TrCP, and an in vivo mouse model was established and used to analyze the effect of β-TrCP on PE clinical phenotypes. ResultsWe found that miR-135a-5p expression was significantly decreased and negatively correlated with β-TrCP expression in the placental tissues of pregnant women with PE. Cellular function experiments showed that overexpression of miR-135a5p promoted the migration and invasion of trophoblast cells in vitro. Furthermore, β-TrCP was confirmed as a target gene of miR-135a-5p in trophoblast cells. Notably, overexpression of β-TrCP significantly reversed the effect of miR-135a-5p on migration and invasion of trophoblast cells. At the molecular level, decreases in E-cadherin levels and increases in N-cadherin, Vimentin, and β-catenin levels that were induced by miR-135a-5p overexpression were attenuated by β-TrCP overexpression. ConclusionsOur findings demonstrate that miR-135a-5p promotes the migration and invasion of trophoblast cells by targeting β-TrCP.

Knockdown of DDX46 inhibits trophoblast cell proliferation and migration through the PI3K/Akt/mTOR signaling pathway in preeclampsia.

Preeclampsia (PE) is a serious disease during pregnancy associated with the dysfunction of trophoblast cell invasion. DDX46 is a kind of RNA helicase that has been found to regulate cancer cell metastasis. However, the role of DDX46 in PE remains unclear. Our results showed that the mRNA levels of DDX46 in placental tissues of pregnant women with PE were markedly lower than those in normal pregnancies. Loss-of-function assays showed that knockdown of DDX46 significantly suppressed cell proliferation of trophoblast cells. Besides, DDX46 knockdown decreased trophoblast cell migration and invasion capacity. In contrast, the overexpression of DDX46 promoted the migration and invasion of trophoblast cells. Furthermore, knockdown of DDX46 caused significant decrease in the levels of p-PI3K, p-Akt, and p-mTOR in HTR-8/SVneo cells. In addition, treatment with IGF-1 reversed the inhibitory effects of DDX46 knockdown on proliferation, migration, and invasion of HTR-8/SVneo cells. In conclusion, these data suggest that DDX46 might be involved in the progression of PE, which might be attributed to the regulation of PI3K/Akt/mTOR signaling pathway. Thus, DDX46 might serve as a therapeutic target for the treatment of PE.

Expression imbalance of IL-17/IL-35 in peripheral blood and placental tissue of pregnant women in preeclampsia

ObjectivesThe possible mechanism of preeclampsia is investigated in this study to facilitate the exploration of the future remediation of this disease by analysing the changes of IL-17 and IL-35 in peripheral blood and placental tissue of pregnant women with preeclampsia (PE). Materials and methodsThe study was conducted using 45 healthy pregnant women as the control group and 90 pregnant women in the preeclampsia group, including 45 cases with severe preeclampsia and 45 cases with mild preeclampsia. All of 135 pregnant women underwent caesarean delivery. IL-17 and IL-35 concentrations in the serum were measured by ELISA, and IL-17 and IL-35 expression in placental specimens was detected by immunohistochemistry. ResultsThere were no statistically significant differences in age among the three study groups. Serum IL-17 levels were significantly higher in PE patients than in healthy pregnant women (P < 0.01). The ratio of positive staining for IL-17 was markedly higher in mild PE tissues (84.44%; 38/45) and severe PE tissues (86.67%; 39/45) than in healthy pregnant tissues (35.56%; 16/45) (P < 0.01). The strong positive rates for IL-17 were markedly higher in mild PE tissues (48.89%; 22/45) and severe PE tissues (68.89%; 31/45) than in healthy pregnant tissues (13.33%; 6/45) (P < 0.01). No differences between mild PE tissues and severe PE tissues were noted in both positive case rates and strong positive rates. Consistent with this finding, the ratio of strong positive staining for IL-35 was higher in healthy pregnant tissues (66.67%; 30/45) than in mild PE tissues (33.11%; 14/45) and severe PE tissues (26.67%; 12/45) (P < 0.01). ConclusionsThe abnormal increase in serum and placental of IL-17 has an association with the formation and development of PE. IL-35 expression is significantly lower in severe PE placenta tissue and serum compared with normal pregnant women. These results suggested that IL-17/IL-35 imbalance may play a role in the pathophysiology of PE.