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American Journal of Obstetrics and... Apr 2024Placenta accreta spectrum disorders are associated with severe maternal morbidity and mortality. Placenta accreta spectrum disorders involve excessive adherence of the...
BACKGROUND
Placenta accreta spectrum disorders are associated with severe maternal morbidity and mortality. Placenta accreta spectrum disorders involve excessive adherence of the placenta preventing separation at birth. Traditionally, this condition has been attributed to excessive trophoblast invasion; however, an alternative view is a fundamental defect in decidual biology.
OBJECTIVE
This study aimed to gain insights into the understanding of placenta accreta spectrum disorder by using single-cell and spatially resolved transcriptomics to characterize cellular heterogeneity at the maternal-fetal interface in placenta accreta spectrum disorders.
STUDY DESIGN
To assess cellular heterogeneity and the function of cell types, single-cell RNA sequencing and spatially resolved transcriptomics were used. A total of 12 placentas were included, 6 placentas with placenta accreta spectrum disorder and 6 controls. For each placenta with placenta accreta spectrum disorder, multiple biopsies were taken at the following sites: placenta accreta spectrum adherent and nonadherent sites in the same placenta. Of note, 2 platforms were used to generate libraries: the 10× Chromium and NanoString GeoMX Digital Spatial Profiler for single-cell and spatially resolved transcriptomes, respectively. Differential gene expression analysis was performed using a suite of bioinformatic tools (Seurat and GeoMxTools R packages). Correction for multiple testing was performed using Clipper. In situ hybridization was performed with RNAscope, and immunohistochemistry was used to assess protein expression.
RESULTS
In creating a placenta accreta cell atlas, there were dramatic difference in the transcriptional profile by site of biopsy between placenta accreta spectrum and controls. Most of the differences were noted at the site of adherence; however, differences existed within the placenta between the adherent and nonadherent site of the same placenta in placenta accreta. Among all cell types, the endothelial-stromal populations exhibited the greatest difference in gene expression, driven by changes in collagen genes, namely collagen type III alpha 1 chain (COL3A1), growth factors, epidermal growth factor-like protein 6 (EGFL6), and hepatocyte growth factor (HGF), and angiogenesis-related genes, namely delta-like noncanonical Notch ligand 1 (DLK1) and platelet endothelial cell adhesion molecule-1 (PECAM1). Intraplacental tropism (adherent versus non-adherent sites in the same placenta) was driven by differences in endothelial-stromal cells with notable differences in bone morphogenic protein 5 (BMP5) and osteopontin (SPP1) in the adherent vs nonadherent site of placenta accreta spectrum.
CONCLUSION
Placenta accreta spectrum disorders were characterized at single-cell resolution to gain insight into the pathophysiology of the disease. An atlas of the placenta at single cell resolution in accreta allows for understanding in the biology of the intimate maternal and fetal interaction. The contributions of stromal and endothelial cells were demonstrated through alterations in the extracellular matrix, growth factors, and angiogenesis. Transcriptional and protein changes in the stroma of placenta accreta spectrum shift the etiologic explanation away from "invasive trophoblast" to "loss of boundary limits" in the decidua. Gene targets identified in this study may be used to refine diagnostic assays in early pregnancy, track disease progression over time, and inform therapeutic discoveries.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Placenta Accreta; Endothelial Cells; Placenta; Placenta Diseases; Abruptio Placentae; Intercellular Signaling Peptides and Proteins; Decidua; Endothelium
PubMed: 38296740
DOI: 10.1016/j.ajog.2023.10.001 -
Placenta Sep 2023The future health of the offspring can be influenced by longstanding maternal anxiety and depression disorders during pregnancy. The present study aimed to explore the...
INTRODUCTION
The future health of the offspring can be influenced by longstanding maternal anxiety and depression disorders during pregnancy. The present study aimed to explore the effect of psychiatric disorders during pregnancy on placental epigenetics.
METHODS
We measured DNA methylation patterns in term-placentas of women either suffering longstanding anxiety and depression symptoms (Index group, with overt symptoms), or a healthy population (Control, none/only mild symptoms). Whole genome DNA methylation profiling was performed using the TruSeq® Methyl Capture EPIC Library Prep Kit (Illumina, San Diego, CA, USA) for library preparation and NGS technology for genomic DNA sequencing.
RESULTS
The results of high-throughput DNA methylation analysis revealed that the Index group had differential DNA methylation at epigenome-wide significance (p < 0.05) in 226 genes in the placenta. Targeted enrichment analyses identified hypermethylation of genes associated with psychiatric disorders (BRINP1, PUM1), and ion homeostasis (COMMD1), among others. The ECM (extracellular matrix)-receptor interaction pathway was significantly dysregulated in the Index group compared to the Control. In addition, DNA methylation/mRNA integration analyses revealed that four genes with key roles in neurodevelopment and other important processes (EPB41L4B, BMPR2, KLHL18, and UBAP2) were dysregulated at both, DNA methylation and transcriptome levels in the Index group compared to Control.
DISCUSSION
The presented results increase our understanding of how maternal psychiatric disorders may affect the newborn through placental differential epigenome, suggesting DNA methylation status as a biomarker when aiming to design new preventive techniques and interventions.
Topics: Infant, Newborn; Humans; Pregnancy; Female; Placenta; Depression; Epigenesis, Genetic; DNA Methylation; Anxiety; RNA-Binding Proteins
PubMed: 37549439
DOI: 10.1016/j.placenta.2023.07.298 -
Frontiers in Endocrinology 2023Placental dysfunction refers to the insufficiency of placental perfusion and chronic hypoxia during early pregnancy, which impairs placental function and causes... (Review)
Review
Placental dysfunction refers to the insufficiency of placental perfusion and chronic hypoxia during early pregnancy, which impairs placental function and causes inadequate supply of oxygen and nutrients to the fetus, affecting fetal development and health. Fetal intrauterine growth restriction, one of the most common outcomes of pregnancy-induced hypertensions, can be caused by placental dysfunction, resulting from deficient trophoblast syncytialization, inadequate trophoblast invasion and impaired vascular remodeling. During placental development, cytotrophoblasts fuse to form a multinucleated syncytia barrier, which supplies oxygen and nutrients to meet the metabolic demands for fetal growth. A reduction in the cell fusion index and the number of nuclei in the syncytiotrophoblast are found in the placentas of pregnancies complicated by IUGR, suggesting that the occurrence of IUGR may be related to inadequate trophoblast syncytialization. During the multiple processes of trophoblasts syncytialization, specific proteins and several signaling pathways are involved in coordinating these events and regulating placental function. In addition, epigenetic modifications, cell metabolism, senescence, and autophagy are also involved. Study findings have indicated several abnormally expressed syncytialization-related proteins and signaling pathways in the placentas of pregnancies complicated by IUGR, suggesting that these elements may play a crucial role in the occurrence of IUGR. In this review, we discuss the regulators of trophoblast syncytialization and their abnormal expression in the placentas of pregnancies complicated by IUGR.
Topics: Pregnancy; Female; Humans; Placenta; Trophoblasts; Fetal Growth Retardation; Placentation; Oxygen
PubMed: 36798658
DOI: 10.3389/fendo.2023.1107182 -
The Journal of Histochemistry and... Apr 2023Preeclampsia is a complication of pregnancy that affects 3-5% of pregnancies and is one of the major causes of maternal/neonatal mortality and morbidities worldwide. We...
Preeclampsia is a complication of pregnancy that affects 3-5% of pregnancies and is one of the major causes of maternal/neonatal mortality and morbidities worldwide. We aimed to investigate the distribution of Foxp3+ regulatory T-cells and CD68+ Hofbauer cells in the placenta of preeclamptic and healthy pregnant women with a special focus on correlating these findings with placental histology. Decidua and chorionic villi of the placenta obtained from healthy and preeclamptic pregnancies were evaluated in full-thickness sections. Sections were stained with hematoxylin and eosin and Masson's trichrome and immunostained for Foxp3 and CD68 for histological analyses. The total histomorphological score for placentas was found to be higher in preeclamptic placentas than that in the controls. The CD68 immunoreactivity was higher in the chorionic villi of preeclamptic placentas than that in the controls. The immunoreactivity of Foxp3 was found widely distributed within the decidua in both the groups and did not differ significantly. Interestingly, Foxp3 immunoreactivity in the chorionic villi was found mainly in the villous core and, to a lesser extent, in the syncytiotrophoblasts. We found no significant relation between Foxp3 expressions and morphological changes observed in preeclamptic placentas. Although extensive research is being carried out regarding the pathophysiology of preeclampsia, the findings are still controversial.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Placenta; Pre-Eclampsia; Trophoblasts; Transcription Factors; Forkhead Transcription Factors
PubMed: 37070940
DOI: 10.1369/00221554231170662 -
Pregnancy Hypertension Mar 2021We aimed at describing placental abruption in our county and at evaluating factors associated with poor fetal outcome. (Observational Study)
Observational Study
OBJECTIVES
We aimed at describing placental abruption in our county and at evaluating factors associated with poor fetal outcome.
STUDY DESIGN
In this case-control study, women with placental abruption were identified from two databases of Brest University Hospital between January 2013 and December 2018.
MAIN OUTCOME MEASURES
Placental histological findings, course of pregnancies, maternal and fetal characteristics were described and compared between cases (placental abruption with stillbirth or neonatal death) and controls.
RESULTS
We identified 135 placental abruption, of whom 24.4% were complicated with stillbirth and 6.5% with neonatal death. Forty percent of women were smokers and 14.1% had a history of vasculoplacental disorder. Pregnancies were complicated with 42.2% of pre-eclampsia and 43% of intrauterine growth restriction. Cases were associated with more autoimmune diseases in mother (20.0% versus 3.2%, P = 0.003), more aspirin or heparin use during pregnancy (20.0% versus 6.3%, P = 0.03), less pre-eclampsia (25.0% versus 49.5%, P = 0.01) and more deliveries ≤ 34 weeks of gestation (80.0% versus 43.2%, P = 0.0001) than controls. Placentas from cases showed more placental indentation ≥ 30% (42.5% versus 5.3%, P < 0.0001) and less histological chronic inflammation, especially less chronic chorioamniotitis (2.5% versus 24.2%, P = 0.002) than controls. In multivariate analysis, factors negatively associated with poor fetal outcome were placental histological chronic inflammation (P = 0.01) and macroscopic infarcts (P = 0.01).
CONCLUSIONS
Poor fetal outcome is negatively associated with certain placental histological chronic lesions, but not with pre-eclampsia, what suggests various pathophysiological processes among placental abruption.
Topics: Abruptio Placentae; Adult; Case-Control Studies; Female; France; Humans; Infant, Newborn; Male; Placenta; Pregnancy; Pregnancy Outcome; Retrospective Studies; Risk Factors
PubMed: 33264704
DOI: 10.1016/j.preghy.2020.11.004 -
Frontiers in Immunology 2021Human cytomegalovirus (HCMV) infects the placenta, and these placental infections can cause fetal injury and/or demise. The timing of maternal HCMV infection during...
Human cytomegalovirus (HCMV) infects the placenta, and these placental infections can cause fetal injury and/or demise. The timing of maternal HCMV infection during pregnancy is a determinant of fetal outcomes, but how development affects the placenta's susceptibility to infection, the likelihood of placental injury post-infection, and the frequency of transplacental HCMV transmission remains unclear. In this study, guinea pig cytomegalovirus (GPCMV) was used to model primary maternal infection and compare the effects of infection at two different times on the placenta. When guinea pigs were infected with GPCMV at either 21- or 35-days gestation (dGA), maternal and placental viral loads, as determined by droplet digital PCR, were not significantly affected by the timing of maternal infection. However, when the transcriptomes of gestational age-matched GPCMV-infected and control placentas were compared, significant infection-associated changes in gene expression were only observed after maternal infection at 35 dGA. Notably, transcripts associated with immune activation (e.g. , , , and ) were upregulated in the infected placenta. A GPCMV-specific hybridization assay detected rare infected cells in the main placenta after maternal infection at either time, and maternal infection at 35 dGA also caused large areas of GPCMV-infected cells in the junctional zone. As GPCMV infection after mid-gestation is known to cause high rates of stillbirth and/or fetal growth restriction, our results suggest that the placenta becomes sensitized to infection-associated injury late in gestation, conferring an increased risk of adverse pregnancy outcomes after cytomegalovirus infection.
Topics: Animals; Cytomegalovirus; Cytomegalovirus Infections; Female; Guinea Pigs; Placenta; Pregnancy; Pregnancy Complications, Infectious; Viral Load
PubMed: 34211475
DOI: 10.3389/fimmu.2021.686415 -
Journal of Reproductive Immunology Jun 2022Galectins are known for their immunomodulatory functions in placentas. They are associated with pregnancy disorders such as preeclampsia, HELLP-Syndrome and intrauterine...
OBJECTIVE
Galectins are known for their immunomodulatory functions in placentas. They are associated with pregnancy disorders such as preeclampsia, HELLP-Syndrome and intrauterine growth restriction (IUGR). In addition, galectins seem to be overexpressed in placentas of women with gestational diabetes mellitus (GDM).
STUDY DESIGN
The collective consisted of 40 women diagnosed with GDM and 40 healthy expectant mothers. The expression of Gal-4 was investigated in syncytiotrophoblast (SCT), representing the fetal part of the placenta, and decidual tissues, representing the maternal part of the placenta, by immunohistochemistry and immunofluorescence double staining. Expression levels were evaluated using the immunoreactive score (IRS).
RESULTS
Nuclear IRS of Gal-4 is significantly higher in SCT cells of placentas of expectant mothers diagnosed with GDM. Overexpression of Gal-4 observed in the decidua of women with GDM by significant higher nuclear and cytoplasmatic IRS of Gal-4. Multivariate regression showed that Gal-4 is significantly overexpressed in the nucleus of SCTs and cytoplasm of decidual cells of placentas with GDM. GDM could be identified as a significant predictor for both cases.
CONCLUSION
The results of this study provide further evidence for the involvement of galectins in the processes of chronic inflammation throughout a pregnancy with GDM. These findings are also in line with the known overexpression of galectin-1 in placental tissues of GDM women. Further evaluation of the role of galectins in this process is warranted.
Topics: Diabetes, Gestational; Female; Galectin 4; Galectins; Humans; Placenta; Pregnancy; Trophoblasts
PubMed: 35468527
DOI: 10.1016/j.jri.2022.103629 -
Biological Trace Element Research May 2020The human placenta is an important organ that forms a barrier where maternal and fetal exchange takes place. The placenta transport iodine to the fetal circulation by...
The human placenta is an important organ that forms a barrier where maternal and fetal exchange takes place. The placenta transport iodine to the fetal circulation by transfer of maternal iodine and deiodination of thyroid hormones (THs). The aim of the study was to examine the distribution of iodine and thyroid hormone transporters in the maternal and fetal sides of human-term placenta. A cross-sectional study was performed at the First Affiliated Hospital of China Medical University. Placental samples (maternal and fetal surfaces) were collected from 113 healthy-term pregnant women. The iodine content; the concentration of thyroxine (T4), triiodothyronine (T3), and reverse T3 (rT3); and the enzyme activity of placental type 2 iodothyronine deiodinase (D2) and D3 were examined. The mRNA and protein localization/expression of iodine and thyroid hormone transporters in the placenta were also studied. We also analyzed the association between expression level of Na+/I- symporter (NIS), thyroid hormone transporter protein, D3 activity in maternal and fetal surfaces of placenta with iodine content, and thyroid hormone levels. Iodine levels in placental samples from the maternal side were significantly higher than those in samples from the fetal side. T3 and T4 expression in fetal placenta was significantly lower than in maternal placenta. D3 activity in the fetal side of the placentas was significantly higher than that in the maternal side. The mRNA and protein expression of monocarboxylate transporters 8 (MCT8), L-amino acid transporters 1 (LAT1), organic anion transporting polypeptides 4A1 (OATP4A1), and TH binding protein transthyretin (TTR) were significantly increased in maternal side, while the NIS expression was higher in fetal side of human-term placenta. In conclusion, the enzymatic deiodination of thyroid hormones forms a barrier which reduces transplacental passage of the hormones and that the maternal part of the placenta is the primary factor in the mechanism regulating the hormonal transfer.
Topics: Adult; Cross-Sectional Studies; Female; Humans; Iodine; Placenta; Placental Circulation; Pregnancy; Thyroid Hormones
PubMed: 31502179
DOI: 10.1007/s12011-019-01834-z -
IEEE Transactions on Visualization and... Jun 2017The human placenta is essential for the supply of the fetus. To monitor the fetal development, imaging data is acquired using (US). Although it is currently the...
The human placenta is essential for the supply of the fetus. To monitor the fetal development, imaging data is acquired using (US). Although it is currently the gold-standard in fetal imaging, it might not capture certain abnormalities of the placenta. (MRI) is a safe alternative for the in utero examination while acquiring the fetus data in higher detail. Nevertheless, there is currently no established procedure for assessing the condition of the placenta and consequently the fetal health. Due to maternal respiration and inherent movements of the fetus during examination, a quantitative assessment of the placenta requires fetal motion compensation, precise placenta segmentation and a standardized visualization, which are challenging tasks. Utilizing advanced motion compensation and automatic segmentation methods to extract the highly versatile shape of the placenta, we introduce a novel visualization technique that presents the fetal and maternal side of the placenta in a standardized way. Our approach enables physicians to explore the placenta even in utero. This establishes the basis for a comparative assessment of multiple placentas to analyze possible pathologic arrangements and to support the research and understanding of this vital organ. Additionally, we propose a three-dimensional structure-aware surface slicing technique in order to explore relevant regions inside the placenta. Finally, to survey the applicability of our approach, we consulted clinical experts in prenatal diagnostics and imaging. We received mainly positive feedback, especially the applicability of our technique for research purposes was appreciated.
Topics: Female; Fetus; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Placenta; Pregnancy; Prenatal Diagnosis
PubMed: 28252405
DOI: 10.1109/TVCG.2017.2674938 -
American Journal of Obstetrics and... Oct 2015Over the past quarter century it has become clear that adult onset chronic diseases like heart disease and type 2 diabetes have their roots in early development. The...
Over the past quarter century it has become clear that adult onset chronic diseases like heart disease and type 2 diabetes have their roots in early development. The report by David Barker and colleagues showing an inverse relationship between birthweight and mortality from ischemic heart disease was the first clear-cut demonstration of fetal programming. Because fetal growth depends upon the placental capacity to transport nutrients from maternal blood, it has been a suspected causative agent since the original Barker reports. Epidemiological studies have shown that placental size and shape have powerful associations with offspring disease. More recent studies have shown that maternal phenotypic characteristics, such as body mass index and height, interact with placental size and shape to predict disease with much more precision than does birthweight alone. For example, among people in the Helsinki Birth Cohort, who were born during 1924–1944, the risk for acquiring colorectal cancer increased as the placental surface became longer and more oval. Among people in whom the difference between the length and breadth of the surface exceeded 6 cm, the hazard ratio for the cancer was 2.3 (95% CI 1.2–4.7, p=0.003) compared with those in whom there was no difference. Among Finnish men, the hazard ratio for coronary heart disease was 1.07 (1.02–1.13, P =0.01) per 1% increase in the placental weight/birthweight ratio. Thus, it appears that the ratio of birthweight to placental weight, known as placental efficiency, predicts cardiovascular risk as well. Babies born with placentas at the extremes of efficiency are more vulnerable for adult onset chronic diseases. Recent evidence suggests that placental growth patterns are sex specific. Boys’ placentas are, in general, more efficient than those made by girls. Another recent discovery is that the size, shape and efficiencies of the placenta can change over years of time with very narrow confidence limits. This suggests that the growth of the placenta within a population of women is strongly affected by their nutritional environment. Even though it is known that an individual placenta can expand to improve its nutrient acquisition capacity in the first 2/3 of gestation, the mechanisms by which placentas grow in response to a specific nutritional environment are not known. Discovering those mechanisms is the task of the current generation of scientists. While it may seem obvious that good nutrition is highly important for women who are pregnant because it supports optimal placentation and fetal development, more research is needed to determine the mechanisms by which maternal nutrition, placenta growth and fetal health are related.
Topics: Animals; Birth Weight; Cardiovascular Diseases; Chorioamnionitis; Chronic Disease; Female; Fetal Development; Glucocorticoids; Humans; Male; Organ Size; Placenta; Pregnancy; Risk Factors; Stress, Physiological
PubMed: 26428494
DOI: 10.1016/j.ajog.2015.08.030