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Journal of the American Heart... Mar 2024Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term...
BACKGROUND
Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth.
METHODS AND RESULTS
Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (=-0.25 to -0.31, all <0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted =0.25-0.47, all <0.05).
CONCLUSIONS
Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.
Topics: Infant, Newborn; Child; Pregnancy; Humans; Female; Placenta; Fetal Development; Brain; Heart Defects, Congenital; Fetal Diseases; Brain Injuries
PubMed: 38420785
DOI: 10.1161/JAHA.123.033189 -
BMC Pregnancy and Childbirth Jun 2020There has been debate about the existence of lymphatic vessels in placenta. Lymphatic endothelial cell (LEC) markers such as LYVE-1 and podoplanin/D2-40 have been found,...
BACKGROUND
There has been debate about the existence of lymphatic vessels in placenta. Lymphatic endothelial cell (LEC) markers such as LYVE-1 and podoplanin/D2-40 have been found, although PROX1 has not been detected. The most reliable marker for LECs is the double staining for CD31 and PROX1, which has not been performed yet.
METHODS
We studied three term placentas and dissected them into three areas: i.) basal plate area, ii.) intermediate area, and iii.) chorionic plate area. We used immunofluorescence single and double staining with antibodies against CD31, PROX1, LYVE-1, VEGFR-3, D2-40/PDPN, CD34, CCBE-1, and vimentin, as well as nested PCR, qPCR, Western blot and transmission electron microscopy (TEM).
RESULTS
At TEM level we observed structures that have previously mistakenly been interpreted as lymphatics, however, we did not find any CD31/PROX1 double-positive cells in placenta. Absence of PROX1 was also noted by nested PCR, qPCR and Western blot. Also, LEC marker VEGFR-3 was expressed only in a small number of scattered leukocytes but was absent from vessels. The LEC marker D2-40/PDPN was expressed in most stromal cells, and the LEC marker LYVE-1 was found in a considerable number of stromal cells, but not in endothelial cells, which were positive for CD31, CD34, CCBE-1 and vimentin. Additionally, vimentin was found in stromal cells.
CONCLUSIONS
Our studies clearly show absence of lymphatics in term placenta. We also show that the functional area of the mother's endometrium is not penetrated by lymphatics in term pregnancy.
Topics: Biomarkers; Endometrium; Endothelial Cells; Female; Humans; Lymphatic Vessels; Membrane Glycoproteins; Placenta; Pregnancy; Transcription Factors; Vascular Endothelial Growth Factor Receptor-3
PubMed: 32600346
DOI: 10.1186/s12884-020-03073-w -
Placenta Sep 2021Impaired placentation is an important contributing factor to intra-uterine growth restriction and pre-eclampsia in fetuses with congenital heart defects (CHD). These...
Impaired placentation is an important contributing factor to intra-uterine growth restriction and pre-eclampsia in fetuses with congenital heart defects (CHD). These pregnancy complications occur more frequently in pregnancies with fetal CHD. One of the most important factors influencing the life of children with CHD is neurodevelopmental delay, which seems to start already in utero. Delayed neurodevelopment in utero may be correlated or even (partly) explained by impaired placentation in CHD cases. This systematic review provides an overview of published literature on placental development in pregnancies with fetal CHD. A systematic search was performed and the Newcastle-Ottawa scale was used to access data quality. Primary outcomes were placenta size and weight, vascular and villous architecture, immunohistochemistry, angiogenic biomarkers and/or placental gene expression. A total of 1161 articles were reviewed and 21 studies were included. Studies including CHD with a genetic disorder or syndrome and/or multiple pregnancies were excluded. Lower placental weight and elevated rates of abnormal umbilical cord insertions were found in CHD. Cases with CHD more frequently showed microscopic placental abnormalities (i.e. abnormal villous maturation and increased maternal vascular malperfusion lesions), reduced levels of angiogenic biomarkers and increased levels of anti-angiogenic biomarkers in maternal serum and umbilical cord blood. Altered gene expression involved in placental development and fetal growth were found in maternal serum and CHD placentas. In conclusion, abnormal placentation is found in CHD. More extensive studies are needed to elucidate the contribution of impaired placentation to delayed neurodevelopment in CHD cases.
Topics: Biomarkers; Female; Fetal Development; Heart Defects, Congenital; Humans; Placenta; Placentation; Pregnancy
PubMed: 34388551
DOI: 10.1016/j.placenta.2021.07.297 -
Pathobiology : Journal of... 2021Since the outbreak of coronavirus disease 2019 (COVID-19), there has been a debate whether pregnant women are at a specific risk for COVID-19 and whether it might be...
Since the outbreak of coronavirus disease 2019 (COVID-19), there has been a debate whether pregnant women are at a specific risk for COVID-19 and whether it might be vertically transmittable through the placenta. We present a series of five placentas of SARS coronavirus 2 (SARS-CoV-2)-positive women who had been diagnosed with mild symptoms of COVID-19 or had been asymptomatic before birth. We provide a detailed histopathologic description of morphological changes accompanied by an analysis of presence of SARS-CoV-2 in the placental tissue. All placentas were term deliveries (40th and 41st gestational weeks). One SARS-CoV-2-positive patient presented with cough and dyspnoea. This placenta showed prominent lymphohistiocytic villitis and intervillositis and signs of maternal and foetal malperfusion. Viral RNA was present in both placenta tissue and the umbilical cord and could be visualized by in situ hybridization in the decidua. SARS-CoV-2 tests were negative at the time of delivery of 3/5 women, and their placentas did not show increased inflammatory infiltrates. Signs of maternal and/or foetal malperfusion were present in 100% and 40% of cases, respectively. There was no transplacental transmission to the infants. In our cohort, we can document different time points regarding SARS-CoV-2 infection. In acute COVID-19, prominent lymphohistiocytic villitis may occur and might potentially be attributable to SARS-CoV-2 infection of the placenta. Furthermore, there are histopathological signs of maternal and foetal malperfusion, which might have a relationship to an altered coagulative or microangiopathic state induced by SARS-CoV-2, yet this cannot be proven considering a plethora of confounding factors.
Topics: Adult; COVID-19; Cohort Studies; Female; Humans; Placenta; Pregnancy; SARS-CoV-2
PubMed: 32950981
DOI: 10.1159/000511324 -
Computerized Medical Imaging and... Sep 2020Post-delivery analysis of the placenta is useful for evaluating health risks of both the mother and baby. In the U.S., however, only about 20% of placentas are assessed...
Post-delivery analysis of the placenta is useful for evaluating health risks of both the mother and baby. In the U.S., however, only about 20% of placentas are assessed by pathology exams, and placental data is often missed in pregnancy research because of the additional time, cost, and expertise needed. A computer-based tool that can be used in any delivery setting at the time of birth to provide an immediate and comprehensive placental assessment would have the potential to not only to improve health care, but also to radically improve medical knowledge. In this paper, we tackle the problem of automatic placental assessment and examination using photos. More concretely, we first address morphological characterization, which includes the tasks of placental image segmentation, umbilical cord insertion point localization, and maternal/fetal side classification. We also tackle clinically meaningful feature analysis of placentas, which comprises detection of retained placenta (i.e., incomplete placenta), umbilical cord knot, meconium, abruption, chorioamnionitis, and hypercoiled cord, and categorization of umbilical cord insertion type. We curated a dataset consisting of approximately 1300 placenta images taken at Northwestern Memorial Hospital, with hand-labeled pixel-level segmentation map, cord insertion point and other information extracted from the associated pathology reports. We developed the AI-based Placental Assessment and Examination system (AI-PLAX), which is a novel two-stage photograph-based pipeline for fully automated analysis. In the first stage, we use three encoder-decoder convolutional neural networks with a shared encoder to address morphological characterization tasks by employing a transfer-learning training strategy. In the second stage, we employ distinct sub-models to solve different feature analysis tasks by using both the photograph and the output of the first stage. We evaluated the effectiveness of our pipeline by using the curated dataset as well as the pathology reports in the medical record. Through extensive experiments, we demonstrate our system is able to produce accurate morphological characterization and very promising performance on aforementioned feature analysis tasks, all of which may possess clinical impact and contribute to future pregnancy research. This work is the first for comprehensive, automated, computer-based placental analysis and will serve as a launchpad for potentially multiple future innovations.
Topics: Benzoates; Female; Fetus; Humans; Neural Networks, Computer; Placenta; Pregnancy; Sodium Dodecyl Sulfate; Umbilical Cord
PubMed: 32634729
DOI: 10.1016/j.compmedimag.2020.101744 -
Ultrasound in Obstetrics & Gynecology :... Mar 2016To evaluate the accuracy of ultrasound in the diagnosis of placenta accreta and its variants, and to assess the impact of prenatal diagnosis in our population. (Comparative Study)
Comparative Study
OBJECTIVES
To evaluate the accuracy of ultrasound in the diagnosis of placenta accreta and its variants, and to assess the impact of prenatal diagnosis in our population.
METHODS
A total of 314 women with placenta previa were enrolled prospectively and underwent transabdominal and transvaginal ultrasound examinations. An ultrasound diagnosis (grayscale and color/power Doppler) of placental attachment disorder (PAD) was based on the detection of at least two of the following ('two-criteria system'): loss/irregularity of the retroplacental clear zone, thinning/interruption of the uterine serosa-bladder wall interface, turbulent placental lacunae with high velocity flow, myometrial thickness < 1 mm, increased vascularity of the uterine serosa-bladder wall interface, loss of vascular arch parallel to the basal plate and/or irregular intraplacental vascularization. Definitive diagnosis was made at delivery by Cesarean section. Maternal outcome in cases diagnosed antenatally was compared with that in cases diagnosed at delivery.
RESULTS
There were 37/314 cases of PAD (29 anterior and eight posterior). The two-criteria system identified 30 cases of placenta accreta, providing a sensitivity of 81.1% and specificity of 98.9%. When anterior and posterior placentae were considered separately, the detection rates of PAD were 89.7 and 50.0%, respectIvely. Maternal outcome was better in women with prenatal diagnosis of PAD, as seen by less blood loss and shorter hospitalization.
CONCLUSIONS
Our data confirmed that grayscale and color Doppler ultrasound have good performance in the diagnosis of PAD and that prenatal diagnosis improves maternal outcome. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Cesarean Section; Female; Humans; Outcome Assessment, Health Care; Placenta; Placenta Accreta; Pregnancy; Prenatal Diagnosis; Prospective Studies; Sensitivity and Specificity; Ultrasonography, Doppler, Color; Ultrasonography, Prenatal; Uterus
PubMed: 25964123
DOI: 10.1002/uog.14893 -
Biology of Reproduction Mar 2022During pregnancy, the immune system is modified to allow developmental tolerance of the semi-allogeneic fetus and placenta to term. Pregnant women suffering from stress,...
During pregnancy, the immune system is modified to allow developmental tolerance of the semi-allogeneic fetus and placenta to term. Pregnant women suffering from stress, anxiety, and depression show dysfunctions of their immune system that may be responsible for fetal and/or newborn disorders, provided that placental gene regulation is compromised. The present study explored the effects of maternal chronic self-perceived stress, anxiety, and depression during pregnancy on the expression of immune-related genes and pathways in term placenta. Pregnancies were clinically monitored with the Beck Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 divided patients into two groups: Index group (>10, n = 11) and a Control group (<10, n = 11), whose placentae were sampled at delivery. The placental samples were subjected to RNA-Sequencing, demonstrating that stress, anxiety, and depression during pregnancy induced a major downregulation of placental transcripts related to immune processes such as T-cell regulation, interleukin and cytokine signaling, or innate immune responses. Expression differences of main immune-related genes, such as CD46, CD15, CD8α & β ILR7α, and CCR4 among others, were found in the Index group (P < 0.05). Moreover, the key immune-like pathway involved in humoral and cellular immunity named "Primary immunodeficiency" was significantly downregulated in the Index group compared with Controls. Our results show that mechanisms ruling immune system functions are compromised at the maternal-fetal interface following self-perceived depressive symptoms and anxiety during pregnancy. These findings may help unveil mechanisms ruling the impact of maternal psychiatric symptoms and lead to new prevention/intervention strategies in complicated pregnancies.
Topics: Anxiety; Depression; Female; Humans; Immunity; Infant, Newborn; Placenta; Pregnancy; Pregnant Women
PubMed: 34935902
DOI: 10.1093/biolre/ioab232 -
Genome Research Jun 2016The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically...
The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilization. There are a large number of germline DMRs that have not yet been associated with imprinting, and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs in the human placenta and investigated the dynamics of these imprinted DMRs during development in somatic and extraembryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 134 human tissue samples, publicly available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. Forty-three known and 101 novel imprinted DMRs were identified in the human placenta by comparing methylation between diandric and digynic triploid conceptions in addition to female and male gametes. Seventy-two novel DMRs showed a pattern consistent with placental-specific imprinting, and this monoallelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation between placental samples. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation.
Topics: DNA Methylation; Female; Genomic Imprinting; Humans; Male; Placenta; Polymorphism, Genetic; Pregnancy; Sequence Analysis, DNA
PubMed: 26769960
DOI: 10.1101/gr.196139.115 -
Placenta Sep 2020Placental Protein 1 (PP1), PP8, and PP22 were isolated from the placenta. Herein, we aimed to identify PP1, PP8, and PP22 proteins and their placental and trophoblastic...
INTRODUCTION
Placental Protein 1 (PP1), PP8, and PP22 were isolated from the placenta. Herein, we aimed to identify PP1, PP8, and PP22 proteins and their placental and trophoblastic expression patterns to reveal potential involvement in pregnancy complications.
METHODS
We analyzed PP1, PP8, and PP22 proteins with LC-MS. We compared the placental behaviors of PP1, PP8, and PP22 to the predominantly placenta-expressed PP5/TFPI-2. Placenta-specificity scores were generated from microarray data. Trophoblasts were isolated from healthy placentas and differentiated; total RNA was isolated and subjected to microarray analysis. We assigned the placentas to the following groups: preterm controls, early-onset preeclampsia, early-onset preeclampsia with HELLP syndrome, term controls, and late-onset preeclampsia. After histopathologic examination, placentas were used for tissue microarray construction, immunostaining with anti-PP1, anti-PP5, anti-PP8, or anti-PP22 antibodies, and immunoscoring.
RESULTS
PP1, PP8, and PP22 were identified as 'nicotinate-nucleotide pyrophosphorylase', 'serpin B6', and 'protein disulfide-isomerase', respectively. Genes encoding PP1, PP8, and PP22 are not predominantly placenta-expressed, in contrast with PP5. PP1, PP8, and PP22 mRNA expression levels did not increase during trophoblast differentiation, in contrast with PP5. PP1, PP8, and PP22 immunostaining were detected primarily in trophoblasts, while PP5 expression was restricted to the syncytiotrophoblast. The PP1 immunoscore was higher in late-onset preeclampsia, while the PP5 immunoscore was higher in early-onset preeclampsia.
DISCUSSION
PP1, PP8, and PP22 are expressed primarily in trophoblasts but do not have trophoblast-specific regulation or functions. The distinct dysregulation of PP1 and PP5 expression in either late-onset or early-onset preeclampsia reflects different pathophysiological pathways in these preeclampsia subsets.
Topics: Adult; Chromatography, Liquid; Female; Humans; Mass Spectrometry; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Proteomics
PubMed: 32747003
DOI: 10.1016/j.placenta.2020.05.013 -
Arthritis Research & Therapy Jun 2022Systemic lupus erythematosus (SLE) can cause placental dysfunctions, which may result in pregnancy complications. Long noncoding RNAs (lncRNAs) are actively involved in...
BACKGROUND
Systemic lupus erythematosus (SLE) can cause placental dysfunctions, which may result in pregnancy complications. Long noncoding RNAs (lncRNAs) are actively involved in the regulation of immune responses during pregnancy. The present study aimed to determine the lncRNA expression profiles in placentas from women with SLE to gain new insights into the underlying molecular mechanisms in SLE pregnancies.
METHODS
RNA sequencing (RNA-seq) analysis was performed to identify SLE-dysregulated lncRNAs and mRNAs in placentas from women with SLE and normal full-term (NT) pregnancies. Bioinformatics analysis was conducted to predict the biological functions of these SLE-dysregulated lncRNAs and mRNAs.
RESULTS
RNA-seq analysis identified 52 dysregulated lncRNAs in SLE placentas, including 37 that were upregulated and 15 downregulated. Additional 130 SLE-dysregulated mRNAs were discovered, including 122 upregulated and 8 downregulated. Bioinformatics analysis revealed that SLE-dysregulated genes were associated with biological functions and gene networks, such as regulation of type I interferon-mediated signaling pathway, response to hypoxia, regulation of MAPK (mitogen-activated protein kinase) cascade, response to steroid hormone, complement and coagulation cascades, and Th1 and Th2 cell differentiation.
CONCLUSIONS
This is the first report of the lncRNA profiles in placentas from SLE pregnancies. These results suggest that the aberrant expression and the potential regulatory function of lncRNAs in placentas may play comprehensive roles in the pathogenesis of SLE pregnancies. SLE-dysregulated lncRNAs may potentially serve as biomarkers for SLE.
Topics: Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Lupus Erythematosus, Systemic; Placenta; Pregnancy; RNA, Long Noncoding; RNA, Messenger
PubMed: 35701843
DOI: 10.1186/s13075-022-02825-7