Similar Datasets
Project description:The human placenta contains two specialized regions: the villous chorion where gases and nutrients are exchanged between maternal and fetal blood, and the smooth chorion (SC) which surrounds more than 70% of the developing fetus but whose cellular composition and function is poorly understood. Here, we use single cell RNA-sequencing to compare the cell types and molecular programs between these two regions in the second trimester human placenta. Each region consists of progenitor cytotrophoblasts (CTBs) and extravillous trophoblasts (EVTs) with similar gene expression programs. While CTBs in the villous chorion differentiate into syncytiotrophoblasts, they take an alternative trajectory in the SC producing a previously unknown CTB population which we term SC-specific CTBs (SC-CTBs). Marked by expression of region-specific cytokeratins, the SC-CTBs form a stratified epithelium above a basal layer of progenitor CTBs. They express epidermal and metabolic transcriptional programs consistent with a primary role in defense against physical stress and pathogens. Additionally, we show that SC-CTBs closely associate with EVTs and secrete factors that inhibit the migration of the EVTs. This restriction of EVT migration is in striking contrast to the villous region where EVTs migrate away from the chorion and invade deeply into the decidua. Together, these findings greatly expand our understanding of CTB differentiation in these distinct regions of the human placenta. This knowledge has broad implications for studies of the development, functions, and diseases of the human placenta.
| S-EPMC9323019 | biostudies-literature
Project description:Regionally distinct trophoblast regulate barrier function and invasion in the human placenta
| PRJNA814711 | ENA
Project description:Mitochondrial dynamics are involved in many cellular events, including the proliferation, differentiation, and invasion/migration of normal as well as cancerous cells. Human placenta-derived mesenchymal stem cells (PD-MSCs) were known to regulate the invasion activity of trophoblasts. However, the effects of PD-MSCs on mitochondrial function in trophoblasts are still insufficiently understood. Therefore, the objectives of this study are to analyze the factors related to mitochondrial function and investigate the correlation between trophoblast invasion and mitophagy via PD-MSC cocultivation. We assess invasion ability and mitochondrial function in invasive trophoblasts according to PD-MSC cocultivation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and extracellular flux (XF) assay. Under PD-MSCs co-cultivation, invasion activity of a trophoblast is increased via activation of the Rho signaling pathway as well as Matrix metalloproteinases (MMPs). Additionally, the expression of mitochondrial function (e.g., reactive oxygen species (ROS), calcium, and adenosine triphosphate (ATP) synthesis) in trophoblasts are increased via PD-MSCs co-cultivation. Finally, PD-MSCs regulate mitochondrial autophagy factors in invasive trophoblasts via regulating the balance between PTEN-induced putative kinase 1 (PINK1) and parkin RBR E3 ubiquitin protein ligase (PARKIN) expression. Taken together, these results demonstrate that PD-MSCs enhance the invasion ability of trophoblasts via altering mitochondrial dynamics. These results support the fundamental mechanism of trophoblast invasion via mitochondrial function and provide a new stem cell therapy for infertility.
| S-EPMC7696686 | biostudies-literature
Project description:The trophoblast is a critical cell for placental development and embryo implantation in the placenta. We previously reported that placenta-derived mesenchymal stem cells (PD-MSCs) increase trophoblast invasion through several signaling pathways. However, the paracrine effects of PD-MSCs on mitochondrial function in trophoblasts are still unclear. Therefore, the objective of the study was to analyze the mitochondrial function of trophoblasts in response to cocultivation with PD-MSCs. The results showed that PD-MSCs regulate the balance between cell survival and death and protect damaged mitochondria in trophoblasts from oxidative stress. Moreover, PD-MSCs upregulate factors involved in mitochondrial autophagy in trophoblast cells. Finally, PD-MSCs improve trophoblast invasion. Taken together, the data indicate that PD-MSCs can regulate trophoblast invasion through dynamic effects on mitochondrial energy metabolism. These results support the fundamental role of mitochondrial energy mechanism in trophoblast invasion and suggest a new therapeutic strategy for infertility.
| S-EPMC9135125 | biostudies-literature
Project description:IntroductionOur previous study has proofed the glucose sensitive gene-thioredoxin-interacting protein (TXNIP) expression was up in the placenta of the patients with gestational diabetes mellitus (GDM), but the pathological mechanisms underlying abnormal TXNIP expression in the placenta of patients with GDM is completely unclear and additional investigations are required to explain the findings we have observed. In the present study, we simulated the high TXNIP expression via introducing the Tet-On "switch" in vitro, approximate to its expression level in the real world, to explore the following consequence of the abnormal TXNIP.MethodsThe expression and localization of TXNIP in the placenta of GDM patients and the health control was investigated via immunofluorescent staining, western blot and RT-qPCR. Overexpression of TXNIP was achieved through transfecting Tet-on system to the human trophoblastic cell line-HTR-8/Svneo cell. TXNIP knockout was obtained via CRISPR-Cas9 method. The cell phenotype was observed via IncuCyte Imaging System and flow cytometry. The mechanism was explored via western blot and RT-qPCR.ResultsThe expression level of TXNIP in the GDM placenta was nearly 2-3 times higher than that in the control. The TXNIP located at trophoblastic cells of the placenta. When the expression of TXNIP was upregulated, the migration and invasion of the cells accelerated, but cell apoptosis and proliferation did not changed compared with the control group. Furthermore, the size of the TetTXNIP cells became larger, and the expression level of Vimentin and p-STAT3 increased in the TetTXNIP cells. All the changes mentioned above were opposite in the TXNIP-KO cells.ConclusionsAbnormal expression of TXNIP might be related to the impairment of the GDM placental function, affecting the migration and invasion of the placental trophoblast cells through STAT3 and Vimentin related pathway; thus, TXNIP might be the potential therapeutic target for repairing the placental dysfunction deficient in GDM patients.
| S-EPMC10084645 | biostudies-literature
Project description:BackgroundSeveral studies have reported microRNAs (miRNAs) could regulate the placental development, though the role and mechanism of miRNAs in the development of non-diabetic macrosomia (NDFMS) remains unclear.MethodsTo identify the aberrantly expressed key miRNAs in placenta of NDFMS, we employed a strategy consisting of initial screening with miRNA microarray and further validation with quantitative RT-PCR assay (qRT-PCR). In vitro cellular model and a mouse pregnancy model were used to delineate the functional effects of key miRNA on proliferation, invasion, and migration.FindingsmiR-141-3p was identified as the key miRNA with expression level significantly higher in placentas of NDFMS compared with those from normal controls. Overexpressed miR-141-3p in HTR-8/SVneo cells contributed to increased cell proliferation, invasion, and migration. miR-141-3p inhibition in HTR-8/SVneo cells resulted in decreased cell proliferation and invasion. Significantly increased infant birth weight was observed in late pregnancy of C57BL/6J mice treated with miR-141-3p agomir. However, no significant difference was found in early pregnancy of C57BL/6J mice treated with miR-141-3p agomir.InterpretationmiR-141-3p could stimulate placental cell proliferation to participate in the occurrence and development of NDFMS.
| S-EPMC6306401 | biostudies-literature
Project description:Preeclampsia (PE) is a pregnancy-related disease defined as onset of hypertension and proteinuria after the 20th week of pregnancy, which causes most maternal and perinatal morbidity and mortality. Although placental dysfunction is considered as the main cause of PE, the exact pathogenesis of PE is not yet fully understood. Long non-coding RNAs (lncRNAs) are implicated in a broad range of physiological and pathological processes, including the occurrence of PE. In this study, we investigated the expression and functions of HIF-1α pathway-related lncRNA-HEIPP (high expression in PE placenta) in the pathogenesis of PE. The expression of lncRNA-HEIPP in the placenta from women who underwent PE was screened by lncRNA microarray and then verified using real-time polymerase chain reaction. Then, the methylation profile of the lncRNA-HEIPP promoter and the enrichment of H3K4me3 binding were assessed by bisulfite pyrosequencing and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction (qPCR) assay, respectively. It was found that the level of lncRNA-HEIPP in the PE placenta was significantly higher than that in normal placenta and was increased in HTR-8/SVneo human trophoblast cells upon hypoxia treatment. Moreover, we reported that H3K4me3 manifested significantly higher promoter occupancy on lncRNA-HEIPP promoter in HTR-8/SVneo cells upon hypoxia treatment and found that the downregulation of lncRNA-HEIPP promoted trophoblast invasion. Our findings suggested that the hypoxia-induced expression of lncRNA-HEIPP mediated by H3K4me3 modification in trophoblast may contribute to the pathogenesis of PE.
| S-EPMC7793904 | biostudies-literature
Project description:Calcitonin gene-related peptide (CALCB), amylin, and adrenomedullin (ADM) belong to a unique group of calcitonin (CALCA)/CALCB family peptides that have overlapping biological effects owing to their structure and cross-reactivity between receptors. CALCB and ADM are expressed in fetoplacental tissues and are important in maintaining normal placental function. Recently, ADM 2 (ADM2)/intermedin was identified as a novel CALCA/CALCB family peptide that functions through CALCB and ADM receptors. ADM2 is expressed in the pituitary, digestive tract, and other organs of vertebrates and reduces blood pressure in both normal and hypertensive rats. We recently reported that the level of immunoreactive ADM2 is significantly upregulated in pregnant rats and that its hypotensive effects are also increased during rat pregnancy. Furthermore, infusion of ADM2 antagonist in pregnant rats causes fetoplacental growth restriction. The objective of this study was to analyze the expression and possible role of ADM2 in human placenta. We show that ADM2 mRNA is expressed in human placenta and that immunoreactive ADM2 is localized in syncytiotrophoblasts, cytotrophoblasts, and endothelial cells throughout human pregnancy. This study also demonstrates that ADM2 enhances the invasion and migration of first-trimester HTR-8SV/neo cells. ADM2 increases the invasive index of HTR-8SV/neo cells by 2.2-fold compared with controls. Taken together, the findings from this study suggest that ADM2 may have a role in the physiology of human pregnancy via regulation of trophoblast invasion and migration.
| S-EPMC2754890 | biostudies-literature
Project description:The aim of this microarray experiment was to compare the overall transcriptomic profile of human placenta derived trophoblast organoid cultures with its tissue of origin, human placental villi. As the placental villi contains both trophoblast and stromal populations, we have included placenta derived stromal cultures in this comparison.
2018-11-28 | E-MTAB-6683 | biostudies-arrayexpress
Project description:The developmental connection between the placenta and certain embryonic organs, such as the heart, is associated with normal pregnancy and complications, but how the placenta governs embryonic cardiogenesis is poorly understood. Trophoblasts fuse into a multinucleated syncytiotrophoblast (SynT) layer, primarily consisting of a placental materno-fetal interface. We identify that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is essential for trophoblast differentiation and fusion into SynT in human trophoblasts and mouse placentas. Moreover, SynT-derived PIBF1 enables the communication between SynT and adjacent vascular cells to develop the vascular network in the primary placenta and further impacts the early development of the embryonic cardiovascular system in an endocrine manner. Thus, SynT-derived factors and SynT itself in the placenta may play crucial roles in the proper organogenesis of other organs in the embryo.
2024-01-06 | GSE229265 | GEO