Placental Tissue Samples Research Articles

Apelin and Visfatin Expression in Placental Tissue in Women With Preeclampsia and Overweight/Obesity.

Preeclampsia (PE) is a multifunctional and multisystem disorder. Several factors favor the development of PE, including obesity. Cytokines are also expressed in the placenta, predisposing to local alterations that favor the development of distinct pathological processes, including PE. This study aimed to evaluate the apelin and visfatin mRNA expression in the placental tissue of women with preeclampsia and overweight/obesity and correlates with maternal and fetal variables. A cross-sectional analytical study was performed with 60 pregnant women and their newborns. Clinical, anthropometric, and laboratory variables were collected. Placental tissue samples were obtained, and the apelin and visfatin mRNA expression levels were assessed by qRT-PCR. The main findings evidenced lower levels of apelin expression in overweight/obese women, accompanied by a negative correlation with BMI and pre-pregnancy weight; a higher expression of apelin was also observed in women with late PE and no personal history of PE. For visfatin levels, higher expression levels were observed in women with late PE and term delivery. Furthermore, a positive correlation was observed between visfatin levels and fetal anthropometric parameters, such as weight, length, and head circumference. Apelin levels were less expressed in overweight/obese women. Apelin and visfatin levels were correlated/associated with maternal-fetal variables.

Aberrant Methylation of the SOD1 GENE, its Expression and Enzyme Activity in the Placenta of Patients with Preeclampsia.

Oxidative stress is involved in the pathogenesis of preeclampsia (PE). Dysregulation of SOD1 may be involved in the pathogenesis of PE. We examined and compared the methylation level of the promoter region (PMR) of the SOD1, gene expression, and enzyme activity of superoxide dismutase (SOD) in both placenta and maternal blood in PE women. A total of 140 blood samples and 40 placental tissue samples from PE and healthy pregnant controls were studied. The PMR of the SOD1 (Methylight PCR method), the expression (Real-time PCR), and its enzyme activity were investigated and compared in two groups. The PMR of the SOD1 gene in the placental tissue of the patients was significantly increased compared to the control group (P= 0.008); this result was accompanied by a decrease in the expression of the gene and a decrease in the activity of the SOD enzyme. Meanwhile, the PMR of the SOD1 gene did not significantly change in the blood samples of the patients (P= 0.95), while a significant decrease in the expression of SOD1 (without a significant change in the SOD activity) was observed. The results showed significant changes in the PMR of the SOD1 gene and gene expression in placenta tissue. The results highlight the role of the placenta in complications during pregnancy and also revealed epigenetics as an important regulatory pathway in the pathogenesis of preeclampsia.

Comparison of methanol fixation versus cryopreservation of the placenta for metabolomics analysis

Methods for collection of placental tissue at room temperature for metabolic profiling are described. Specimens were excised from the maternal side of the placenta and immediately flash frozen or fixed and stored for 1, 6, 12, 24, or 48 h in 80% methanol. Untargeted metabolic profiling was performed on both the methanol-fixed tissue and the methanol extract. Data were analyzed using Gaussian generalized estimating equations, two sample t-tests with false discovery rate (FDR) corrections, and principal components analysis. Methanol-fixed tissue samples and methanol extracts had a similar number of metabolites (p = 0.45, p = 0.21 in positive vs. negative ion mode). In positive ion mode, when compared to flash frozen tissue, both the methanol extract and methanol-fixed tissue (6 h) had a higher number of metabolites detected (146 additional metabolites, pFDR = 0.020; 149 additional metabolites, pFDR = 0.017; respectively), but these associations were not found in negative ion mode (all pFDR ≥ 0.05). Principle components analysis demonstrated separation of the metabolite features in the methanol extract, but similarity between methanol-fixed tissue and flash frozen tissue. These results show that placental tissue samples collected in 80% methanol at room temperature can yield similar metabolic data to flash frozen specimens.

The correlation between serum levels and placental tissue expression of PLGF and sFLT-1 and the FIGO grading of the placenta accreta spectrum disorders

Objective This study aims to further explore the role of angiogenic vs anti-angiogenic factors in placenta accreta spectrum (PAS). Methods This cohort study included all patients with placenta previa and placenta accreta spectrum (PAS) disorders undergoing surgery at Dr. Soetomo Hospital (Academic Hospital of Universitas Airlangga, Surabaya, Indonesia) from May to September 2021. Venous blood samples for PLGF and sFlt-1 were drawn immediately prior to surgery. Placental tissue samples were taken during surgery. The FIGO grading was diagnosed intraoperatively by an experienced surgeon and confirmed by the pathologist and followed by immunohistochemistry (IHC) staining. The sFlt-1 and PLGF serum were performed by an independent laboratory technician. Results Sixty women were included in this study (20 women with placenta previa; 10 women with FIGO PAS grade 1; 8 women with FIGO PAS grade 2; 22 women with FIGO PAS grade 3). The median with 95% Confidence interval of PLGF serum values in placenta previa, FIGO grade I, grade II, and grade III were 233.68 (0.00–2434.00), 124.39 (10.42–663.68), 236.89 (18.83–418.99) and 237.31 (2.26–3101.00) (p = .736); the median values with 95% CI of serum sFlt-1 levels in placenta previa, FIGO grade I, grade II, and grade III were 2816.50 (418.00–12925.00), 2506.00 (227.50-16104.00), 2494.50 (888.52–20812.00), and 1601.00 (662.16–9574.00) (p = .037). Placental PLGF expression in placenta previa, FIGO grade 1, grade II, and grade III showed median values (with 95% CI) of 4.00 (1.00-9.00), 4.00 (2.00–9.00), 4.00 (4.00–9.00), and 6.00 (2.00–9.00) (p = .001); sFlt-1 expression median values (with 95% CI) were 6.00 (2.00–9.00), 6.00 (2.00–9.00), 4.00 (1.00–9.00), and 4.00 (1.00–9.00) (p = .004). Serum PLGF and sFlt-1 levels did not correlate with placental tissue expression (p = .228; p = .586). Conclusion There are differences in PAS's angiogenic processes ​according to the severity of trophoblast cell invasion. But there is no overall correlation between serum levels and PLGF and sFlt-1 expression in the placenta, suggesting the imbalance between angiogenic and anti-angiogenic are local mechanisms in the placental and the uterine wall.

Alterations in Antioxidant Micronutrient Concentrations in Placental Tissue, Maternal Blood and Urine and the Fetal Circulation in Pre-eclampsia.

Trace elements such as selenium and zinc are vital components of many enzymes, including endogenous antioxidants, and can interact with each other. Women with pre-eclampsia, the hypertensive disease of pregnancy, have been reported as having changes in some individual antioxidant trace elements during pregnancy, which are related to maternal and fetal mortality and morbidity. We hypothesised that examination of the three compartments of (a) maternal plasma and urine, (b) placental tissue and (c) fetal plasma in normotensive and hypertensive pregnant women would allow identification of biologically significant changes and interactions in selenium, zinc, manganese and copper. Furthermore, these would be related to changes in the angiogenic markers, placental growth factor (PlGF) and Soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) concentrations. Venous plasma and urine were collected from healthy non-pregnant women (n = 30), normotensive pregnant controls (n = 60) and women with pre-eclampsia (n = 50) in the third trimester. Where possible, matched placental tissue samples and umbilical venous (fetal) plasma were also collected. Antioxidant micronutrient concentrations were measured by inductively coupled plasma mass-spectrometry. Urinary levels were normalised to creatinine concentration. Plasma active PlGF and sFlt-1 concentrations were measured by ELISA. Maternal plasma selenium, zinc and manganese were all lower in women with pre-eclampsia (p < 0.05), as were fetal plasma selenium and manganese (p < 0.05 for all); maternal urinary concentrations were lower for selenium and zinc (p < 0.05). Conversely, maternal and fetal plasma and urinary copper concentrations were higher in women with pre-eclampsia (p < 0.05). Differences in placental concentrations varied, with lower overall levels of selenium and zinc (p < 0.05) in women with pre-eclampsia. Maternal and fetal PlGF were lower and sFlt-1 higher in women with pre-eclampsia; maternal plasma zinc was positively correlated with maternal plasma sFlt-1 (p < 0.05). Because of perceptions that early- and late-onset pre-eclampsia have differing aetiologies, we subdivided maternal and fetal data accordingly. No major differences were observed, but fetal sample sizes were small following early-onset. Disruption in these antioxidant micronutrients may be responsible for some of the manifestations of pre-eclampsia, including contributing to an antiangiogenic state. The potential benefits of mineral supplementation, in women with deficient intakes, during pregnancy to reduce pre-eclampsia remain an important area for experimental and clinical research.

Placental Barrier on Cadmium Transfer from Mother to Fetus in Related to Pregnancy Complications.

As two of the most severe and common medical disorders during pregnancy, gestational diabetes mellitus (GDM) and hypertensive disorder complicating pregnancy (HDCP) cause adverse effects on placental barrier function and thus may lead to a high risk of intrauterine exposure to toxic metals from mother to fetus. This study investigates the impact of the placental barrier on the transfer of cadmium (Cd) from mother to fetus and the relationship between pregnancy complications. A total of 107 pairs of samples were collected in Kunming, China; 29 were from healthy pregnant women, and 78 were from patients with pregnancy complications. Cd was measured in each mother's placenta and maternal and umbilical cord blood. The expressions of MT and Cd-MT complex in blood and placental tissue samples were determined by enzyme-linked immunosorbent assay (ELISA). The cesarean section rate in the whole pathological group (60.7%) was higher than that in the normal group (20.7%), and the ratio of the effective barrier (ratio of maternal blood to umbilical cord blood>1) in the pathological group (74%) was lower than that in the normal group (79%). In addition, the proportion of practical placental barriers in women aged 20-25 years was 83.3%, 76.3% in women aged 26-30 years, 74.3% in women aged 31-35 years, 70% in women aged 36-40 years, and 71% in women aged 40-45 years. The Cd content in the placenta of the three pathological groups was significantly higher than that in maternal and umbilical cord blood (P<0.05), and the distribution of Cd was the same as that in the normal group. However, there was no significant difference between maternal and umbilical cord blood Cd concentrations in the pathological group. The Cd concentration in the normal group's maternal blood was significantly higher than that in cord blood (P<0.05). In addition, the expression levels of both metallothionein (MT) and Cd-MT complex in placenta is much higher than in maternal and umbilical blood, and which in normal group are significantly higher than those in pathological group. Both mothers and fetuses are at increased health risk for pregnancy disorders when maternal age, BMI, or body weight increases. Increased maternal age increases the likelihood of Cd transfer from the mother to the fetus. Pregnancy complications may induce lower expression of MT, thus reducing the Cd-MT complex in the placenta, weakening the placental barrier, and increasing the risk of Cd transfer and exposure to the fetus.

Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2: Current Evidence and Perspectives

Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2: Current Evidence and Perspectives

Altered Expression of the HLA-G and IL10RB Genes in Placental Tissue of Women with Recurrent Pregnancy Loss.

Several lines of evidence strongly suggest that the contribution of human leukocyte antigen-G (HLA-G) and interleukin 10 receptor (IL10R) to maternal immunological tolerance toward paternal alloantigens of the embryo limits the activation and function of the maternal immune system. This study is aimed to assess the varia-tion of the mRNA expression levels of HLA-G and IL10RB genes in placental tissue of women with recurrent pregnancy loss (RPL). Placental tissue samples were collected from 78 women with a history of at least two consecutive miscarriages and 40 healthy women with no history of pregnancy loss. The expression of HLA-G and IL10RB in placental tissue specimens was evaluated by the quantitative real-time PCR (qPCR) method. Moreover, the correlation be-tween the expression levels of these genes and clinicopathological parameters was analyzed. The results showed that the expression of HLA-G was down-regulated in placental tissues samples of RPL patients compared to healthy subjects, while the expression of IL10RB was up-regulated, but none of them was statistically significant (p-value > 0.05). The mRNA expression levels of HLA-G and IL10RB in placental tissue of RPL patients were negatively correlated with age and number of miscarriages (p-value > 0.05). A significant positive correlation was observed between the expression levels of HLA-G and IL10RB in women with RPL (p-value < 0.05). The altered expression of HLA-G and IL10RB in placental tissue may contribute to the pathogenesis of RPL and therefore serve as potential therapeutic targets for its prevention.

Использование поляризационно-интерференционной микроскопии для определения оптических свойств фетальных эритроцитов в тканях

Objective: to evaluate the possibility of using polarization interference microscopy for morphological diagnostics of fetal erythrocytes in tissues. Materials and methods. Blood smears used during the diagnostic and treatment process and histological sections prepared from autopsy material were used. During the diagnosis, a polarization-interference microscope PZO BIOLAR PI with a microphotometric nozzle UPI was used to determine the optical density and the measure of light transmission in erythrocytes. The method of polarization-interference microscopy contributed to the study of optical properties in individual erythrocytes. The optical properties of erythrocytes containing fetal-type hemoglobin and erythrocytes with adult-type hemoglobin were compared. The difference in the composition of the structure of erythrocytes determined the difference in light transmission and refraction. Based on the results of light transmission, the optical density of fetal and adult erythrocytes was calculated. In the conducted study of clinical blood smears, in neonatal patients, 60 measurements of the light transmission coefficient and 60 similar studies were performed in patients of the comparison group - persons older than 18 years. In the study of autopsy material, 120 measurements of the erythrocyte light transmission coefficient were carried out in placental tissue samples (chorionic villi and interstitial space). Results. The optical properties of erythrocytes were determined both in blood smears and in placental tissue preparations. Erythrocytes in blood smears with HbF had an increased light transmission coefficient in relation to the optical properties of erythrocytes with HbA in the control group. During the study of placental tissues, it was revealed that the indicators of the optical density of maternal erythrocytes with HbA in the erythrocytes of the interstitial space differed in higher values of indicators compared with the optical density of fetal erythrocytes with HbF in the vessels of chorionic villi. Conclusion. The determination of differences in the physico-optical properties of erythrocytes with fetal and adult hemoglobins makes it possible to determine the affiliation of erythrocytes both in blood smears and in the interstitial space of the placenta.

MORPHOMETRIC CHARACTERISTICS OF PLACENTA IN WOMEN WITH PREECLAMPSIA AND OBESITY COMPARED TO WOMEN WITH NORMAL BODY WEIGHT.

The aim: to investigate the morphometric characteristics of placentas in women with comorbidity of preeclampsia and obesity compared to women with physiological body weight, and to assess the efficacy of the prophylactic therapy course developed to prevent the occurrence of preeclampsia in pregnant women with obesity. Materials and methods: 25 biopsy samples of placental tissue were taken from women between 37 and 40 weeks of gestation with a physiological body weight and with class II obesity. The women were divided into five groups of five women in each: the 1st group included women with physiological body weight without obstetric and somatic pathology; the 2nd group involved women with physiological body weight, whose pregnancy was complicated with preeclampsia; the 3rd group was made up of women with class II obesity whose pregnancy was complicated with preeclampsia; the 4th group consisted of women with class II obesity, who received the special prophylactic therapy course, and the 5th group included women with class II obesity, who did not receive the prophylactic therapy course. Results: The analysis of morphometric parameters of placenta samples taken from women with preeclampsia and obesity demonstrates a number of com-pensatory and adaptive changes in placenta under hypoxic conditions, and the most important of them include a significant decrease in the number and the mean diameter of the terminal villi, the reduction of volume of villious tree, an increase in the diameter of the capillaries of terminal villi. The morphometric parameters and histological structure in placenta samples from women with obesity, who received the special the prophylactic therapy course, as well as in placenta samples of the control group were similar to the gestational normative values. Conclusions: The morphometric investigation of placenta samples taken from women with comorbidity of preeclampsia and obesity has shown a significant decrease in the mean diameter of the terminal villi and an increase in the diameter of the capillaries of these terminal villi when compared with a group of women with preeclampsia and physiological body weight. The study has also demonstrated the distortion of the percentage ratio of the volume of the intervil¬lous space and the ratio of medium-calibre villi. The combination of these changes indicates a lack of adaptive capabilities in the placenta during preeclampsia under increasing hypoxic condition.

Correlative multiscale microCT-SBF-SEM imaging of resin-embedded tissue.

Three-dimensional biological microscopy presents a trade-off between spatial resolution and field of view. Correlative approaches applying multiple imaging techniques to the same sample can therefore mitigate against these trade-offs. Here, we present a workflow for correlative microscopic X-ray microfocus computed tomography (microCT) and serial block face scanning electron microscopy (SBF-SEM) imaging of resin-embedded tissue, using mammalian placental tissue samples as an example. This correlative X-ray and electron microscopy (CXEM) workflow allows users to image the same sample at multiple resolutions, and target the region of interest (ROI) for SBF-SEM based on microCT. We detail the protocols associated with this workflow and demonstrate its application in multiscale imaging of horse placental villi and ROI selection in the labyrinthine zone of a mouse placenta. These examples demonstrate how the protocol may need to be adapted for tissues with different densities.

Maternal exposure to polystyrene microplastics alters placental metabolism in mice.

The rapid growth in the worldwide use of plastics has resulted in a vast accumulation of microplastics in the air, soil and water. The impact of these microplastics on pregnancy and fetal development remains largely unknown. In pregnant mice, we recently demonstrated that exposure to micro- and nanoplastics throughout gestation resulted in significant fetal growth restriction. One possible explanation for reduced fetal growth is abnormal placental metabolism. To evaluate the effect of maternal exposure to microplastics on placental metabolism. In the present study, CD-1 pregnant mice were exposed to 5 μm polystyrene microplastics in filtered drinking water at one of four concentrations (0 ng/L (controls), 102 ng/L, 104 ng/L, 106 ng/L) throughout gestation (n = 7-11/group). At embryonic day 17.5, placental tissue samples were collected (n = 28-44/group). Metabolite profiles were determined using 1H high-resolution magic angle spinning magnetic resonance spectroscopy. The relative concentration of lysine (p = 0.003) and glucose (p < 0.0001) in the placenta were found to decrease with increasing microplastic concentrations, with a significant reduction at the highest exposure concentration. Multivariate analysis identified shifts in the metabolic profile with MP exposure and pathway analysis identified perturbations in the biotin metabolism, lysine degradation, and glycolysis/gluconeogenesis pathways. Maternal exposure to microplastics resulted in significant alterations in placental metabolism. This study highlights the potential impact of microplastic exposure on pregnancy outcomes and that efforts should be made to minimize exposure to plastics, particularly during pregnancy.

WNT5A, β‑catenin and SUFU expression patterns, and the significance of microRNA deregulation in placentas with intrauterine growth restriction.

Placental insufficiency is a common cause of intrauterine growth restriction (IUGR). It affects ~10% of pregnancies and increases fetal and neonatal morbidity and mortality. Although Wnt and Hh pathways are crucial for embryonic development and placentation, their role in the pathology of IUGR is still not sufficiently explored. The present study analyzed the expression of positive regulators of the Wnt pathway, WNT5A and β‑catenin, and the expression of the Hh pathway negative regulator suppressor of fused (SUFU). Immunohistochemical and reverse transcription‑quantitative PCR (RT‑qPCR) assays were performed on 34 IUGR and 18 placental tissue samples from physiologic singleton‑term pregnancies. Epigenetic mechanisms of SUFU gene regulation were also investigated by methylation‑specific PCR analysis of its promoter and RT‑qPCR analysis of miR‑214‑3p and miR‑378a‑5p expression. WNT5A protein expression was higher in endothelial cells of placental villi from IUGR compared with control tissues. That was also the case for β‑catenin protein expression in trophoblasts and endothelial cells and SUFU protein expression in trophoblasts from IUGR placentas. The SUFU gene promoter remained unmethylated in all tissue samples, while miR‑214‑3p and miR‑378a‑5p were downregulated in IUGR. The present results suggested altered Wnt and Hh signaling in IUGR. DNA methylation did not appear to be a mechanism of SUFU regulation in the pathogenesis of IUGR, but its expression could be regulated by miRNA targeting.

LncRNA LINC00534 regulates cell proliferation and migration via the miR-494-3p/PTEN axis in HTR-8/SVneo cells.

LncRNA LINC00534 has been found to be differentially expressed in placental tissue samples of preeclampsia (PE), but the exact mechanism is still unclear. In vitro assays were carried out in HTR-8/SVneo cells using various methods, including cell counting kit-8 (CCK-8), transwells, flow cytometry, and Western blotting (WB) and quantitative polymerase chain reaction. RNA pull-down and bioinformatics analysis were applied to examine other potential underlying mechanisms involved. We found that there was a high expression of LINC00534 in the placental tissues of patients with PE. LINC00534 overexpression (OE) significantly inhibited cell proliferation and migration as well as accelerated cell apoptosis in HTR8/SVneo cells. The knockdown of LINC00534 produced an opposite trend. Mechanistically, LINC00534 promoted the expressions of PTEN (Phosphatase and tensin homolog) through decreasing miR-494-3p. Further rescue studies showed that LINC00534 played a role by targeting mir-494-3p, which controlled the growth and migration of HTR-8/SVneo trophoblast cells via regulating PTEN/PI3K/AKT (Phosphatidylinositol3-kinase/protein kinase B). Moreover, lncRNA pull-down assay identified 198 potential bound proteins for LINC00534. Those proteins were mostly involved in RNA processing and modification, posttranslational modification, protein turnover, and chaperones. Overall, by suppressing HTR8/SVneo cell growth and migration via the miR-494-3p/PTEN axis and other mechanisms, LINC00534 offers new insight into PE pathogenesis.

Serological and Molecular Detection of Toxoplasma Gondii among Pregnant Women Giving Birth at the University Of Gondar Specialized Hospital in Gondar Town, Northwest Ethiopia

Objective: Congenital toxoplasmosis can be presented when immunosuppressed women are reactivating of this infection acquired before pregnancy in addition to women recently exposed to this disease during pregnancy, which causes of fetal death, neonatal death or congenital defects. Women mainly get this infection by ingested improperly cooked or raw meat consisting of viable tissue cysts or by contaminated foods and water within sporulated oocysts or through the placenta. Thus, this study aimed to detect Toxoplasma gondii in pregnant women using serologically and molecularly at study area. Methods: A cross-sectional study was conducted from September 2019 to October 2020 by collecting a total of 200 umbilical cord blood and matching discharged placental tissue samples from systematic randomly selected pregnant women giving birth at University of Gondar specialized hospital. Latex agglutination test and nested polymerase chain reaction were used for the detections of this infection. Findings: The overall serological, first polymerase chain reaction and nested polymerase chain reaction findings of this study were 46%, 24% and 10%, respectively. The univariant analysis indicated that seropositivity of Toxoplasma gondii antibodies were also significantly influenced by eating raw meat, eating raw vegetables, drinking raw milk, presence of domestic cat contacts and source of water (P  0.05). In the case of multivariate analysis drinking raw milk and source of water were also significantly associated to the seropositivity of Toxoplasma gondii. Moreover, there were also fair concordant between latex agglutination within first polymerase reaction (Kappa: 0.290) andnested polymerase chain reaction tests of this parasite (Kappa: 0.231). Novelty: This nested polymerase chain reaction and the Toxo-latex agglutination tests had also fair agreements in pregnant women. Moreover, Consumption of raw meat, vegetables and milk; domestic cat contacts and source of water were the potential statically significant associated risk factors for Toxoplasma gondii seropositivity. Conclusions: Generally, these comparative tests confirmed the existence of this infection in pregnant women that played up a pool of public health risks for their embryo and infants. Thus, thoroughly cooking raw meats and vegetables; pasteurized raw milk; avoid domestic cat contacts and boiling of water will be the best prevention and control strategies of this infection. Further works on its genotyping of this pathogen will be also convinced. Keywords: Latex agglutination; Nested polymerase chain reaction; Placental tissue; Pregnant women; Toxoplasma gondii; Umbilical cord blood

WTAP dysregulation-mediated HMGN3-m6A modification inhibited trophoblast invasion in early-onset preeclampsia.

Early-onset preeclampsia (ePE) originates from abnormal implantation and placentation that involves trophoblast invasion, but its pathophysiology is not entirely understood. N6-methyladenosine (m6A) regulators mediate the progression of various cancers. The invasiveness of trophoblast cells is similar to that of tumor cells. However, little is known regarding the potential role of m6A modification in ePE and the underlying mechanism. This study aimed to explore the m6A level in placental tissue samples collected from ePE patients and to investigate whether m6A modification was an essential part of PE pathogenesis. The m6A level in placental tissue samples of 80 PE participants was examined. MeRIP-microarray, RNA-Seq, luciferase reporter assay, and RNA immunoprecipitation chip (RIP) assay were performed. The m6A level in the ePE group was significantly reduced compared with the control group. Wilms' tumor 1-associating protein (WTAP) regulated trophoblast cell migration and invasion. Mechanistically, the high mobility group nucleosomal binding domain 3 (HMGN3) gene was a target gene of WTAP in trophoblast (p < .05). WTAP enhanced the stability of HMGN3 mRNA through binding with its 3'-UTR m6A site(+485A, +522A). HMGN3 was recognized by m6A recognition protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which was inhibited when knocking down WTAP. Both m6A and WTAP levels were downregulated in ePE. The m6A modification mediated by WTAP/IGF2BP1/HMGN3 axis might contribute to abnormal trophoblast invasion. Our work provided a foundation for further exploration of RNA epigenetic regulatory patterns in ePE, and indicated a new treatment strategy for ePE.

Sex-dependent differential transcript expression in the placenta of growth restricted infants

IntroductionThe pathological decrease of fetal growth during gestation can lead to subsequent poor health outcomes for the fetus. This process is commonly controlled by the placenta, the interface between mother and baby during gestation. Sex-specific gene expression has been implicated in placental function, therefore, there is a need to determine if it is important during reduced fetal growth. We therefore aimed to characterise placental gene expression at term to evaluate sex-specific genetic changes that occur in small for gestational age (SGA) infants. MethodsRNA-sequencing of twelve human placental tissue samples collected from pregnancies yielding either term appropriate for gestational age (AGA) or SGA infants identified at delivery. Candidate genes associated with fetal size and fetal sex were identified using differential gene expression and weighted gene co-expression network analyses. Single-cell sequencing data was used for candidate validation and to estimate candidate transcript expression in specific placental cell populations. ResultsDifferential gene expression and weighted gene co-expression network analyses identified 403 candidate transcripts associated with SGA infants. One hundred and three of these transcripts showed sex-specific expression. . Published placental sequencing datasets were used to validate the key expression results from the twelve placental samples initially studied; the sex-independent transcript expression for genes involved in cell cycle processes in males (7 transcripts) and endoplasmic reticulum stress in females (17 transcripts). DiscussionThis study identified the activation of multiple molecular mechanisms involved in the placental response to an adverse environmental stressor. Mechanisms such as disrupted protein synthesis were shared between infant biological sex when comparing AGA to SGA, whilst other pathways such as cell cycle and endoplasmic reticulum stress appear as independent/specific to either males or females when investigating reduced fetal growth. This data suggests that sexual dimorphism is an important consideration when examining placental dysfunction and poor fetal growth.

Increased Expression of NLRP3 Inflammasome in Placentas of Gestational Hypertension

Node like receptor pyrin 3 is a tripartite protein composed an amino terminal pyrin domin (PYD), nucleotide binding NACHT domine and a carboxy terminal leucinerich repeat (LRR) domine, and consider an intracellular sensor that detects a broad range signal and resulting in the formation and activation the NLRP3 inflammasome. This complex lead to release of the inflammatory cytokines IL-1β, IL-18 which is important for host defense against invading pathogen. Modern evidence indicates that the NLRP3 inflammasome involved in gestational hypertension. This study was conducted on fifty pregnant women and divided into two groups, 25 placentas from normotensive mother having no hypertension before as control group and 25 from gestational hypertension women as gestational hypertension group, obtained from Department of Obstetrics and Gynecology in Almosil El Aam Hospital and Alkhanssa Teaching Hospital, Mosul city, Iraq. The placental tissue samples were collected from central region and processed for immunohistochemical technique to expression of NLRP3 in placental tissue. The immunohistochemical study of placenta of gestational hypertension group showed the localization of NLRP3 protein and staining intensity in trophoblast, stroma and endothelium villi were high quantification compared with placenta from control group.

Increased Expression of NLRP3 Inflammasome in Placentas of Gestational Hypertension

Node like receptor pyrin 3 is a tripartite protein composed an amino terminal pyrin domin (PYD), nucleotide binding NACHT domine and a carboxy terminal leucinerich repeat (LRR) domine, and consider an intracellular sensor that detects a broad range signal and resulting in the formation and activation the NLRP3 inflammasome. This complex lead to release of the inflammatory cytokines IL-1β, IL-18 which is important for host defense against invading pathogen. Modern evidence indicates that the NLRP3 inflammasome involved in gestational hypertension. This study was conducted on fifty pregnant women and divided into two groups, 25 placentas from normotensive mother having no hypertension before as control group and 25 from gestational hypertension women as gestational hypertension group, obtained from Department of Obstetrics and Gynecology in Almosil El Aam Hospital and Alkhanssa Teaching Hospital, Mosul city, Iraq. The placental tissue samples were collected from central region and processed for immunohistochemical technique to expression of NLRP3 in placental tissue. The immunohistochemical study of placenta of gestational hypertension group showed the localization of NLRP3 protein and staining intensity in trophoblast, stroma and endothelium villi were high quantification compared with placenta from control group.

Placental Histopathology in COVID-19-Positive Mothers.

The placenta is a captivating multifunctional organ of fetal origin and plays an essential role during pregnancy by intimately connecting mother and baby. This study explicates placental pathology and information about 25 placentas collected from the mothers infected with novel coronavirus (SARS-COV-2). So far, congenital transmission of SARS-CoV-2 seems to be remarkably uncommon in spite of many cases of COVID-19 during pregnancy. Out of the 25 placental tissue samples collected, none has shown gene expression of SARS-CoV-2 when confirmed by RT-PCR. At the same time, nasal and throat swab samples collected from newborns of SARS-CoV-2-positive mothers correspondingly tested negative by RT-PCR. The shielding properties of placental barriers against viral infections from mothers to newborns remains a mystery. Major histopathological findings have been recorded as choriodecidual tissue with necrosis, intramural fibrin deposition, chorionic villi with fibrosis, and calcification. Moreover, although recent findings are insufficient to prove direct placental transmission of COVID-19, the abundance of angiotensin-converting enzymes-2 (ACE-2) on the placental surface could potentially contribute to unpleasant outcomes during pregnancy as SARSCoV-2 gains access to human cells via ACE-2. Finally, the significance of these findings is vague and needs further study.