-
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 -
Placenta Jan 2011Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the...
Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the human placenta, and how it is altered developmentally and pathologically. We examined D2-40/podoplanin and VEGFR-3 expressions in placentas from normotensive pregnancies at different gestational ages and in placentas from women with clinically defined preeclampsia. D2-40 expression in systemic lymphatic vessel endothelium served as a positive control. Protein expression for D2-40, VEGFR-3, and β-actin was determined by Western blot in placentas from normotensive (n = 6) and preeclamptic (n = 5) pregnancies. Our results show that D2-40/podoplanin was strongly expressed in the placenta, mainly as a network plexus pattern in the villous stroma throughout gestation. CD31 was limited to villous core fetal vessel endothelium and VEGFR-3 was found in both villous core fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was significantly decreased, and VEGFR-3 significantly increased in preeclamptic placental tissues compared to normotensive placental controls. Placental villous stroma is a reticular-like structure, and the localization of D2-40 to the stroma suggests that a lymphatic-like conductive network may exist in the human placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is known regarding biological functions of sialylated glycoproteins within the placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during placenta development and reduced D2-40/podoplanin expression in preeclamptic placenta may contribute to altered interstitial fluid homeostasis and impaired angiogenesis in this pregnancy disorder.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Case-Control Studies; Chorionic Villi; Down-Regulation; Female; Humans; Membrane Glycoproteins; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Stromal Cells
PubMed: 21095001
DOI: 10.1016/j.placenta.2010.10.014 -
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 -
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 -
Placenta Feb 2016The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental...
INTRODUCTION
The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta.
METHODS
The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization.
RESULTS
Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs).
DISCUSSION
Together these defects indicate that Hectd1 is required for development of the labyrinthine zonethe mouse placenta.
Topics: Animals; Female; Giant Cells; Mice; Mice, Knockout; Placenta; Placenta Diseases; Placentation; Pregnancy; Trophoblasts; Ubiquitin-Protein Ligases
PubMed: 26907377
DOI: 10.1016/j.placenta.2015.12.002 -
Frontiers in Endocrinology 2022During pregnancy, arterial hypertension may impair placental function, which is critical for a healthy baby's growth. Important proteins during placentation are known to...
INTRODUCTION
During pregnancy, arterial hypertension may impair placental function, which is critical for a healthy baby's growth. Important proteins during placentation are known to be targets for O-linked β-N-acetylglucosamine modification (O-GlcNAcylation), and abnormal protein O-GlcNAcylation has been linked to pathological conditions such as hypertension. However, it is unclear how protein O-GlcNAcylation affects placental function and fetal growth throughout pregnancy during hypertension.
METHODS
To investigate this question, female Wistar and spontaneously hypertensive rats (SHR) were mated with male Wistar rats, and after pregnancy confirmation by vaginal smear, rats were divided into groups of 14, 17, and 20 days of pregnancy (DOPs). On the 14th, 17th, and 20th DOP, rats were euthanized, fetal parameters were measured, and placentas were collected for western blot, immunohistochemical, and morphological analyses.
RESULTS
SHR presented a higher blood pressure than the Wistar rats (p=0.001). Across all DOPs, SHR showed reduced fetal weight and an increase in small-for-gestational-age fetuses. While near-term placentas were heavier in SHR (p=0.006), placental efficiency decreased at 17 (p=0.01) and 20 DOPs (p<0.0001) in this group. Morphological analysis revealed reduced junctional zone area and labyrinth vasculature changes on SHR placentas in all DOPs. O-GlcNAc protein expression was lower in placentas from SHR compared with Wistar at 14, 17, and 20 DOPs. Decreased expression of O-GlcNAc transferase (p=0.01) and O-GlcNAcase (p=0.002) enzymes was found at 14 DOPs in SHR. Immunohistochemistry showed reduced placental O-GlcNAc content in both the junctional zone and labyrinth of the placentas from SHR. Periodic acid-Schiff analysis showed decreased glycogen cell content in the placentas from SHR at 14, 17, and 20 DOPs. Moreover, glucose transporter 1 expression was decreased in placentas from SHR in all DOPs.
CONCLUSIONS
These findings suggest that decreased protein O-GlcNAcylation caused by insufficient placental nutritional apport contributes to placental dysfunction during hypertensive pregnancy, impairing fetal growth.
Topics: Female; Pregnancy; Rats; Male; Animals; Placenta; Rats, Wistar; Rats, Inbred SHR; Placentation; Hypertension; Nutrients
PubMed: 36531508
DOI: 10.3389/fendo.2022.1032499 -
Indian Journal of Pathology &... 2023Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with the onset or first recognition during pregnancy and is the most common metabolic...
BACKGROUND
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with the onset or first recognition during pregnancy and is the most common metabolic complication of pregnancy. Significant maternal and fetal complications can result from undiagnosed or inadequately treated GDM.
AIM
To investigate the difference in the expression of the CD-68 marker in the Hofbauer cells (HCs) and their distribution within the villi in the placentas of diabetic and non-diabetic mothers.
MATERIALS AND METHODS
Sixty placentas were included in the study, 30 as controls and 30 from mothers with diagnosed GDM as cases. Full-thickness cross sections of placentas were obtained. Tissue processing was done, followed by haematoxylin and eosin (H&E). A study of CD68 markers (placental macrophages) was done using standard protocols of immunohistochemistry.
STATISTICAL ANALYSIS
Frequencies and percentages of Hofbauer cells (HCs) found in case and control placental tissue were calculated. Student's t-test was used to compare two groups using SPSS 13.0 software. When P is 0.0001, differences were considered statistically significant.
RESULTS AND CONCLUSION
We studied the distribution and number of fetal macrophages (CD68+) in diabetic and non-diabetic placentas. The immunostained CD68+ cell count was identified to be significantly higher in the GDM placenta. In relation to fetal blood vessels in the villus stroma of the GDM placenta in comparison to control, CD68+ cells were found more frequently. This study shows a significant increase in the number of Hofbauer cells in the placenta of mothers with GDM in comparison to control (P < 0.0001). An increase in macrophages in these placentae might be related to the protective mechanism against inflammation. Further studies are required to investigate the mechanism in detail.
Topics: Female; Humans; Pregnancy; Case-Control Studies; Diabetes, Gestational; Immunohistochemistry; Macrophages; Placenta
PubMed: 38084523
DOI: 10.4103/ijpm.ijpm_99_22 -
PloS One 2014The serum amyloid A (SAA) protein is known to function in the acute phase response and immunoregulation. Recently, SAA has been shown to be involved in cell...
The serum amyloid A (SAA) protein is known to function in the acute phase response and immunoregulation. Recently, SAA has been shown to be involved in cell proliferation, differentiation and migratory behavior in different cell types. Here, we evaluated whether exogenous SAA could influence trophoblast invasion and differentiation using both the trophoblast-like BeWo cell line and fully differentiated human extravillous trophoblast cells (EVT) isolated from term placentae. SAA stimulated BeWo cell invasion, as measured in Matrigel invasion assays, and induced metalloprotease mRNA expression and activity. Given that BeWo cells express Toll-like receptor 4 (TLR4), a known receptor for SAA, we examined the role of TLR4 in SAA-induced invasion using a TLR4 neutralizing antibody. We also tested whether SAA could affect markers of trophoblast syncytialization in BeWo cells. We observed that SAA decreased βhCG secretion and did not influence trophoblast syncytialization. Using EVT cells isolated from human term basal plates, we confirmed that SAA at 1 and 10 µg/mL doubled EVT invasion in a TLR4-dependent manner, but at 20 µg/mL inhibited EVT cells invasiveness. In addition, we observed that SAA was expressed in both BeWo cells and human term placentae, specifically in the syncytiotrophoblast, decidual cells and EVT. In conclusion, SAA was identified as a molecule that functions in the placental microenvironment to regulate metalloprotease activity and trophoblast invasion, which are key processes in placentation and placental homeostasis.
Topics: Cell Line; Cell Movement; Female; Giant Cells; Humans; Placenta; Pregnancy; Serum Amyloid A Protein; Trophoblasts
PubMed: 24614130
DOI: 10.1371/journal.pone.0090881 -
International Journal of Molecular... Nov 2023While exercise (EX) during pregnancy is beneficial for both mother and child, little is known about the mechanisms by which maternal exercise mediates changes in utero....
While exercise (EX) during pregnancy is beneficial for both mother and child, little is known about the mechanisms by which maternal exercise mediates changes in utero. Six-week-old female C57BL/6 mice were divided into two groups: with (exercise, EX; N = 7) or without (sedentary, SED; N = 8) access to voluntary running wheels. EX was provided via 24 h access to wheels for 10 weeks prior to conception until late pregnancy (18.5 days post coitum). Sex-stratified placentas and fetal livers were collected. Microarray analysis of SED and EX placentas revealed that EX affected gene transcript expression of 283 and 661 transcripts in male and female placentas, respectively (±1.4-fold, < 0.05). Gene Set Enrichment and Ingenuity Pathway Analyses of male placentas showed that EX led to inhibition of signaling pathways, biological functions, and down-regulation of transcripts related to lipid and steroid metabolism, while EX in female placentas led to activation of pathways, biological functions, and gene expression related to muscle growth, brain, vascular development, and growth factors. Overall, our results suggest that the effects of maternal EX on the placenta and presumably on the offspring are sexually dimorphic.
Topics: Animals; Female; Male; Mice; Mice, Inbred C57BL; Mothers; Placenta; Signal Transduction; Exercise
PubMed: 38003633
DOI: 10.3390/ijms242216441