recurrent decidual cast

Lun ATL, et al. K-means cluster analysis was performed in MeV v4.8 (6) to group marker genes based on co-expression across cell state clusters. Apart from generating a temporal map of TF and effector genes underpinning progression of cells along the decidual pathway, the network analysis also revealed that multiple genes involved in immune surveillance of senescent cells, including CXCL14, IL-15 and TIMP-3, are hardwired to be activated prior to the emergence of snDC. I have a history of endometriosis in my family. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. BJOG. The number and distribution pattern of plasma cells stained with CD138 in decidual tissue in 10 high-power fields (HPFs) was examined. Taken together, the data show that complex networks of co-regulated genes underpin progression of cells along the decidual pathway and suggest that altered expression levels of PGR co-regulators, such as FOSL2 and STAT1, may account for progesterone-dependency of DC and progesterone-resistance of snDC. The biological mechanisms of these events have yet to be researched. A survey studied has been published on one particular symptom reported: decidual cast shedding. not pregnant. There are multiple mechanisms by which chronic senescent cells promote tissue dysfunction, including perturbation of stem cells, disruption of ECM, induction of tissue inflammation, and propagation of senescence in neighbouring cells25,27,32. Recurrent pregnancy loss (RPL) is one of the big challenges of normal pregnancy. 1g). The numbers of plasma cells (meanstandard error) in 10 HPFs of decidual tissue is 0.520.17 and 14.05.88 (P<0.01) in Non-CE and CE patients, respectively. d Schematic representation of uNK-cell co-culture experiments. Our analysis also enabled a definition of putative defects across the pathway, including decidualization failure (SCARA5: 30th percentile, DIO2: 30th percentile), excessive decidual senescence (SCARA5: 30th percentile, DIO2: 70th percentile), and uNK cell deficiency (uNK cells: 30th percentile, SCARA5 and DIO2: >30th<70th percentile) (Fig. The incidence rate of CD of grade2+3 was significantly higher in CE than Non-CE (53.8%; 7/13 vs. 0%; 0/13, P<0.01). PMC legacy view Reply Recurrent decidual cast with membranous dysmenorrhea. A doctor whos willing to play ball with recurrent loss testing is worth keeping at least until you get your results. The specific inhibitors for Erk, p38 and JNK against the MAPK pathway were added to the co-culture media to evaluate the functions of the Erk, p38 and JNK. Figure-of-merit (FOM) was run first to determine the number of expression patterns (k). National Library of Medicine volume20, Articlenumber:114 (2020) Single-cell reconstruction of the early maternal-fetal interface in humans. Gellersen B, Brosens JJ. Cells were cultured on tissue culture-treated plastic with media changed every 48h. Cells were passaged at sub-confluence by 5min treatment with 0.25% Trypsin-EDTA. Bayer-Garner IB, Korourian S. Plasma cells in chronic endometritis are easily identified when stained with syndecan-1. As depicted in Fig. 5a). NADPH oxidase-derived reactive oxygen species mediate decidualization of human endometrial stromal cells in response to cyclic AMP signaling. f Secretion of CLU in decidualized (C+M) cells co-cultured with uNK cells relative to decidualized cells cultured without uNK cells. Tewary, S. et al. a Decidual gene network B2 annotated to highlight genes implicated in uNK-cell activation and immune surveillance of senescence cells. cDNA was eluted in 12l nuclease-free water and quality and size assessed using an Agilent Bioanalyzer High Sensitivity DNA chip (Agilent, Stockport, UK). Trapnell C, et al. Jun JI, Lau LF. Progestin regulates chemokine (C-X-C motif) ligand 14 transcript level in human endometrium. Immunostaining with CD138 for endometrial tissue was performed according to previous reports [17, 26]. The lining of the uterine wall is called decidua and it sheds in the triangular shape resembling the uterus wall called cast It looks pretty strange because it is a combination of L19 was used as a reference control. Stained slides were de-hydrated, cleared and cover-slipped in a Tissue-Tek Prisma Automated Slide Stainer, model 6134 (Sakura Flinetek Inc., CA, USA) using DPX coverslip mountant. Recently we reported loss of clonal mesenchymal stem-like cells (MSC) in midluteal endometrium of RPL patients but how this is linked to subsequent breakdown of the decidualplacental interface in pregnancy is unclear33. <> The numbers of plasma cells (meanstandard error of the mean) in 10 HPFs of decidual tissue were 0.540.24 and 14.05.88 (P<0.01) in the Non-CE and CE groups, respectively (Fig. For potential or actual medical emergencies, immediately call 911 or your local emergency service. All samples were obtained with written informed consent and in accordance with The Declaration of Helsinki (2000) guidelines. Biopsies were timed relative to the pre-ovulatory luteinizing hormone (LH) surge to coincide with the midluteal implantation window (LH+8; n=3) or the start of the late-luteal phase (LH+10; n=3). Am J Reprod Immunol. 1d and Supplementary Fig. CRYAB, HSD11B1 and GLRX)3537 were enriched in S5 (designated DC) whereas genes involved in oxidative stress signalling and cellular senescence, including KIAA1199, CLU and ABI3BP3841, prevailed in S6 (designated snDC) (Fig. As shown in Fig. Kaku, S., Kubo, T., Kimura, F. et al. Reverse transcription was performed from 1g RNA using the Quantitect Reverse Transcription Kit (QIAGEN, Manchester, UK) and cDNA was diluted to 10ng/l equivalent before use in qPCR. The flow-through was cultured in DMEM/F12 with phenol red containing 10% DCC, 1X Antibiotic-Antimycotic mix, L-glutamine, estradiol and insulin (growth medium). Pediatr Dev Pathol. De Vivo Antonio, Mancuso Alfredo, Giacobbe Annamaria, et al. Recently, we demonstrated that decidualization also results in the emergence of senescent decidual cells (snDC), both in vitro and in vivo9,24. As shown in Fig. SAG activity in cultured cells was quantified using the 96-Well Cellular Senescence Activity Assay kit (CBA-231, Cell Biolabs Inc, CA, USA) as described previously9. Childs Bennett G., Gluscevic Martina, Baker Darren J., Laberge Remi-Martin, Marquess Dan, Dananberg Jamie, van Deursen Jan M. Senescent cells: an emerging target for diseases of ageing. When we chose 1 for m (the ratio of control to experimental subjects for independent prospective studies), the calculation resulted in sample sizes of 12 cases for the control group and 12 cases for the affected group. Doctors typically provide answers within 24 hours. Informed written consent was obtained for publication. Why did I pass a decidual cast? For these, please consult a doctor (virtually or in person). official website and that any information you provide is encrypted Our data suggest that DC must engage uNK cells to eliminate snDC to escape this default pathway, although additional in vivo studies are required to substantiate this conjecture. Altered transcriptional regulation of cytokines, growth factors, and apoptotic proteins in the endometrium of infertile women with chronic endometritis. A total of 5000 uNK cells were added to 50,000 EnSC, decidualized or not, per well of a 96-well plate. 2 Decidual bleeding does occur in some women but is fairly rare. Network A1 genes are rapidly downregulated within the first 48h of the decidual process after which expression remains largely stable. <> 2000;31:2925. I am sexually active. Taken together, the incidence of an aberrant decidual response (i.e. 1), 4580 cells were assigned to 7 transcriptional cell states using Shared Nearest Neighbour (SNN) and t-Distributed Stochastic Neighbour Embedding (t-SNE) methods. Tal R, et al. To examine if an aberrant decidual response in cycling endometrium is linked to increased risk of pregnancy loss, we analysed LH-timed endometrial biopsies from 90 control subjects and 89 RPL patients. Ritschka B, et al. See the June 13th discussion on this subject held on Good Morning CHD, Participate in the#CanWeTalkAboutIt Campaign. DCS is historically a rare gynecological event, with less than 40 cases reported in the medical literature over the last 109 years. Am J Reprod Immunol. The effect of chronic endometritis remains in the decidua of more than half of miscarriage cases, which are considered to be chronic deciduitis with a cluster or a number of plasma cells. Recovering gene interactions from single-cell data using data diffusion. d. Grade 3 CD, 20 or more plasma cells with more than 5 clusters in 10 HPFs. The predictive power of the k-means algorithm was estimated using an FOM values for k from 1 to 20. 6c). maybe endometriosis? We hypothesized that MSC deficiency may drive a pro-senescent decidual response during the peri-implantation window, culminating in chronic inflammation in early pregnancy, proteolysis of the decidualplacental interface, and miscarriage. Part of The mucus membrane lining the uterus is known as a decidua once it is implanted with a fertilized egg. The ratios of Grade 1 CD were 30.8% (4/13) and 15.4% (2/13) (P=0.64) in the Non-CE group and CE group, respectively (Table 1). 2009;12:1621. FFPE tissue sections were stained for CD56 (a uNK-cell-specific cell surface antigen) using a 1:200 dilution of concentrated CD56 antibody (NCL-L-CD56-504, Novocastra, Leica BioSystems). The diagnosis of CD is similar to that of CE, depending histologically on the presence of plasma cells in the decidua [19, 20]. Song JJ, et al. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Lash GE, et al. In the total cases of Grade 2 and Grade 3 CD, the incidence of CE before the pregnancy was 100%. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Thus, a critical challenge at implantation is to simultaneously avoid imminent endometrial breakdown while transforming the cycling endometrium into a semi-permanent tissue, the decidua, maintained throughout pregnancy. EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data. Cochr Database Syst Rev. Control subjects were considered to have good prognosis; patients with recurrent implantation failure, defined as three or more consecutive IVF failures with good quality embryos, were excluded. Reprod Biol Endocrinol. This precipitous transcriptomic response is in keeping with an acute cellular stress response and coincided with a transient rise in IL-6 and IL-8 secretion independent of transcription (Supplementary Fig. For the past 2 weeks I've been having constant stabbing like pains in my ovaries/pelvis. Black solid lines indicate the median level of secretion. and K.F. GPX3, PAEP and DPP4) (Fig. Google Scholar. Failure to do so leads to chronic senescence, at least in culture. 1e and Supplementary Table1). Placenta. (to F.K.). Black solid lines indicate the median level of secretion. Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells. PLoS One. Content on HealthTap (including answers) should not be used for medical advice, diagnosis, or treatment, and interactions on HealthTap do not create a doctor-patient relationship. about navigating our updated article layout. a The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. 2010;93:397404. Notably, IGFBP1, a widely used decidual marker gene8, was also part of this module. Initial Drop-Seq data processing was performed using Drop-Seq_tools-1.0.1 following the protocol described by Nemesh (seqAlignmentCookbook_v1.2Jan2016.pdf, http://mccarrolllab.com/dropseq). Networks are annotated for selected transcription factor genes with core roles in decidualization. Images were obtained using an EVOS AUTO microscope (ThermoFisher Scientific) with a 40 objective lens. Gilmore H, Fleischhacker D, Hecht JL. official website and that any information you provide is encrypted We also demonstrated that snDC rapidly convert DC into secondary senescent cells, a process abrogated by co-cultured uNK cells. The analysis of the presence of CD in the specimens of miscarriage may help subsequent fertility treatment. To study the effect of CE on decidua in cases of miscarriage. The hysteroscopy and histological diagnosis and treatment value of chronic endometritis in recurrent implantation failure patients. I had an intense amount of pain and then suddenly saw this & some other pieces right after. Samples were analysed by BD FACSMelody Cell Sorter (BD Biosciences) and data analysis was performed using FlowJo v10. The top 10 differentially expressed genes (DEG) between the 7 cell states are presented as a heatmap (Supplementary Fig. Bianco AC, Kim BW. a Schematic representation of in vitro time-course experiment. Finally, we report a conspicuous link between a pro-senescent decidual response in peri-implantation endometrium and recurrent pregnancy loss, suggesting that pre-pregnancy screening and intervention may reduce the burden of miscarriage. Approximately 15% of clinical pregnancies result in miscarriage1, most often during the first trimester. The experimental design is depicted in Fig. Arch Gynecol Obstet. Decidualizing cells then progressed in synchrony to S4 by day 4 after which they segregated into two transcriptionally distinct subsets, S5 and S6 (Fig. MeSH Primer sequences were as follows: SCARA5 forward: 5-CATGCG TGG GTT CAA AGG TG-3, SCARA5 reverse: 5-CCA TTC ACC AGG CGG ATC AT-3; DIO2 forward: 5-ACT CGG TCA TTC TGC TCA A-3, DIO2 reverse: 5-TTC CAG ACG CAG CGC AGT-3, L19 forward: 5-GCG GAA GGG TAC AGC CAA T-3, L19 reverse: 5-GCA GCC GGC GCA AA-3. Temporal changes in chromosome abnormalities in human spontaneous abortions: results of 40 years of analysis. To test this hypothesis, uNK cells were isolated from the supernatants of freshly cultured EnSC using magnetic-activated cell sorting (MACS) and the purity and viability of cells confirmed by flow cytometry (Supplementary Fig. Thank you, I've never had it happen before. Chronic inflammation of the placenta: definition, classification, pathogenesis, and clinical significance. The Drop-Seq data were deposited in the GEO repository (http://www.ncbi.nlm.nih.gov/geo/ with accession number: {"type":"entrez-geo","attrs":{"text":"GSE127918","term_id":"127918"}}GSE127918). The intracellular cytokines of decidual PD-1 + and PD-1- T cells were evaluated by flow cytometric analysis. Clusters were designated based on canonical marker genes as endothelial cells (EC; n=141), epithelial cells (EpC; n=395), immune cells (IC; n=352) and EnSC (n=1943) (Fig. Before Characteristic of the decidual CD56+ NK during early normal pregnancy and recurrent spontaneous abortion. Hardy K, Hardy PJ, Jacobs PA, Lewallen K, Hassold TJ. However, so far, there has been no reports of how the endometrium of CE patients changes during pregnancy. Standardisation of uterine natural killer (uNK) cell measurements in the endometrium of women with recurrent reproductive failure. However, SCARA5AVERAGE/DIO2AVERAGE samples consisted of mixture of SCARA5+ or DIO2+ cells as well as intermediate cells expressing both transcripts. O'herlihy C. Reviewing maternal deaths to make motherhood safer: 2006-2008. Raneros AB, et al. 3). This is when a piece of the uterine lining sheds and passes out of the body. f Decidualizing EnSC were placed in pseudotime to reconstruct the trajectory of differentiation, revealing a continuous trajectory towards senescence with a single branch point marking the divergence of DC. BMJ (Clin Res Ed). Conceptualization: J.J.B. CAS Carp H, et al. Our in vitro analysis suggested that the default trajectory of decidualizing EnSC is towards cellular senescence, which can only be avoided by timely clearance of snDC by uNK cells. First, DC and snDC both emerge in response to FOXO1 activation, a pivotal decidual transcription factor downstream of the protein kinase A (PKA) and progesterone signalling pathways. 50% off with $15/month membership Cell barcodes beyond the inflection point are believed to represent ambient RNA (e.g. 2). Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. Background The presence of chronic deciduitis (CD) was determined in patients diagnosed with or without chronic endometritis (CE) before pregnancy. Keywords: The beginning of pseudotime is in the middle of the heatmap and the trajectory towards DC and snDC are indicated by the arrows. Obstetrics and Gynecology 23 years experience. Int J Gynecol Pathol. Induction of 11beta-HSD 1 and activation of distinct mineralocorticoid receptor- and glucocorticoid receptor-dependent gene networks in decidualizing human endometrial stromal cells. Ultra sound yesterday showed fibroids. Chemokine signaling via the CXCR2 receptor reinforces senescence. Analysis of co-regulated gene networks indicated that a switch in PGR co-regulators from FOSL2 to STAT1 may account for progesterone-resistance in snDC, although this conjecture will need to be tested experimentally. Few interventions improve live-birth rates in RPL5, reflecting that in most cases the underlying mechanisms are incompletely understood. Nothing on this website should be construed as medical or legal advice. Single-cell transcriptomes were captured in aqueous droplets containing barcoded beads using a microfluidic system (scRNA-seq: Dolomite Bio, Royston, UK) according to the manufacturers protocol and based on the Drop-Seq method described by Macosko and colleagues34. Fuminori Kimura. In addition, it has been reported that the ongoing pregnancy rate is restored when CE is cured with antibiotic treatment, suggesting that the cause of CE is microbial infection [9, 12,13,14,15]. 1 : the part of the endometrium that in higher placental mammals undergoes special modifications in preparation for and during pregnancy and is cast off at parturition. When CD with cluster or five or more of plasma cells is confirmed histologically in miscarriage decidual tissue, the presence of CE before the pregnancy should be suspected. Samples were obtained during the luteal phase of ovulatory, non-hormonally stimulated menstrual cycles, timed relative to the pre-ovulatory LH surge, using a Wallach Endocell endometrial sampler. However, there was a significant difference in the incidence of Grade 2+Grade 3 CD. Get prescriptions or refills through a video chat, if the doctor feels the prescriptions are medically appropriate. New insights into the mechanisms underlying recurrent pregnancy loss. ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence. ELISAs were performed on spent medium collected at 48h intervals to examine secreted levels of CXCL14, IL-15 and TIMP-3. Endometrial biopsies were collected in DMEM-F12 media supplemented with 10% dextran-coated charcoal-stripped FBS (DCC) and processed for primary EnSC culture as described9. Differential gene expression on the selected cells was determined using the Seurat function FindMarkers employing the Wilcoxon test, with GO analysis performed using DAVID66. t-SNE projection of 4580 EnSC, colour-coded according to days of decidualization (D0-8) and upon withdrawal (WD) of the differentiation signal for 48h. D0 represents undifferentiated EnSC. contaminating RNA from damaged cells), not cellular transcriptomes, and therefore excluded from further analysis. Accessibility Chronic senescent cells accumulate progressively in response to various stressors and cause gradual loss of organ function during ageing mediated by the deleterious effects of the SASP on tissue homoeostasis25,27. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. Please note, we cannot prescribe controlled substances, diet pills, antipsychotics, or other commonly abused medications. Recently we demonstrated that snDC exhibit hallmarks of acute senescent cells9. As shown in Fig. By ICWA / June 13, 2022 June 13, 2022. Apart from a discrete population of proliferative cells (S1), the bulk of undifferentiated EnSC were in S2. Informed consent was obtained from the patients. Dobin A, et al. 4a). sharing sensitive information, make sure youre on a federal More research is urgently needed to investigate the factors contributing to DCS in 2021 and whether this trend is continuing. http://creativecommons.org/licenses/by/4.0/. Learn the causes, diagnosis, and outlook for this uncommon Grey dotted lines indicate secreted levels in individual cultures (n=4). Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure. CD is pathologically diagnosed with the presence of plasma cells within the decidua (decidual endometrium). 9). 3 0 obj We compared the percentage of CD56+ NK in the lymphocyte population of the non-pregnant endometrium and decidual tissue of placentas, received after medical abortion and after recurrent spontaneous abortion. Stress-resistant decidual cells recruit and activate uNK cells to eliminate stressed/senescent decidual cells through granule exocytosis. Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy. Immunohistochemistry of CD138 for decidual tissue. 2015;30:32330. ; methodology: P.V., E.S.L, J.L. Four independent EnSC cultures were used. Centile calculations were performed on dCt values using R v3.5 software. Severe Round ligament pain for 3months. 3e). Similarly, the ratios of Grade 2 CD were 0% (0/13) and 30.8% (4/13) (P=0.48), respectively, and the proportions of Grade 3 CD were 0% (0/13) and 23.1% (0/13) (P=0.22), respectively (Table 1). It can cause extreme discomfort as well as vaginal bleeding as it leaves your body. This conclusion was based on the observation that endometrial fibroblasts isolated from marsupials, which diverted from eutherians 60 to 80 million years ago56, activate similar core regulatory genes as human EnSC in response to a decidualizing stimulus and then mount an acute stress response akin to the initial decidual phase19. To explore the switching of DC into snDC further, we ordered decidualizing cells (D2-8) in pseudotime and colour-coded them by transcriptional state. Unable to load your collection due to an error, Unable to load your delegates due to an error. Be mindful of any unusual symptoms that may occur when you take contraceptives, like severe cramps and vaginal bleeding. will also be available for a limited time. Eluted libraries were analysed using Agilent Bioanalyzer High Sensitivity DNA chip to assess quality and determine library size, and concentration was determined by Qubit High Sensitivity DNA assay. Vento-Tormo R, et al. Six LH-timed endometrial biopsies were processed as described in detail above and elsewhere9. Amplification was performed on a 7500 Real-Time PCR system (Applied Biosystems, Paisley, UK) in 20l reactions using 2PrecisionPlus Mastermix with SYBR Green and low ROX (PrimerDesign, Southampton, UK), with 300nM each of forward and reverse primers. By rejecting non-essential cookies, Reddit may still use certain cookies to ensure the proper functionality of our platform. e SAG activity in undifferentiated and decidualized (C+M) cells co-cultured with or without uNK cells. PubMed 2016;105:10610. Grade 1 CD was found in 4/13 Non-CE patients who miscarried. Next, we examined the frequency of different putative defects along the decidual pathway. 4b). Whats wrong with me! and J.J.B. Murphy FA, Lipp A, Powles DL. RNA in situ hybridization was carried with RNAscope 2.5 HD Duplex Reagent Kit (ACD, California, USA) with probes for SCARA5 (574781-C1) and DIO2 (562211-C2) according to manufacturers guidelines. The total sample size for analysis was 6049 with 89.1% of the participants responding within the first 3.5 months of the 7.5 months duration of the study. We used k-means cluster analysis to identify networks of co-regulated genes across the decidual pathway (Supplementary Data3). According to the results of the present study, CD with the presence of a cluster or a number of plasma cells was frequently found when a CE patient became pregnant and miscarried. Proliferation of uterine natural killer cells is induced by human chorionic gonadotropin and mediated via the mannose receptor. At a molecular level, decidual transformation of EnSC encompasses genome-wide remodelling of the chromatin landscape13, reprogramming of multiple signalling pathways1416, and activation of decidual gene networks17,18. 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