Glucose metabolism by human placental villi.
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ABSTRACT:
SUBMITTER: DiPietro DL
PROVIDER: S-EPMC1270392 | biostudies-other | 1967 Apr
REPOSITORIES: biostudies-other
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Project description: Not available
| EMPIAR-10967 | biostudies-other
Project description:Maintenance of a healthy pregnancy is reliant on a successful balance between the fetal and maternal immune systems. Although the maternal mechanisms responsible have been well studied, those used by the fetal immune system remain poorly understood. Using suspension mass cytometry and various imaging modalities, we report a complex immune system within the mid-gestation (17-23 weeks) human placental villi (PV). Consistent with recent reports in other fetal organs, T cells with memory phenotypes, although rare in abundance, were detected within the PV tissue and vasculature. Moreover, we determined that T cells isolated from PV samples may be more proliferative after T cell receptor stimulation than adult T cells at baseline. Collectively, we identified multiple subtypes of fetal immune cells within the PV and specifically highlight the enhanced proliferative capacity of fetal PV T cells.
| S-EPMC8935213 | biostudies-literature
Project description:Placental function is essential for fetal development and establishing the foundations for lifelong health. The placental villous stroma is a connective tissue layer that supports the fetal capillaries and villous trophoblast. All the nutrients that cross the placenta must also cross the stroma, and yet little is known about this region. This study uses high-resolution three-dimensional imaging to explore the structural complexity of this region within the placental villi. Serial block-face scanning electron microscopy and confocal microscopy were used to image the placental villous stroma in three-dimensions. Transmission electron microscopy (TEM) was used to generate high resolution two-dimensional images. Stereological approaches were used to quantify volumes of stromal constituents. Three-dimensional imaging identified stromal extracellular vesicles, which constituted 3.9% of the villous stromal volume. These stromal extracellular vesicles were ovoid in shape, had a median length of 2750 nm (range 350-7730 nm) and TEM imaging confirmed that they were bounded by a lipid bilayer. Fifty-nine per cent of extracellular vesicles were in contact with a fibroblast-like stellate cell and these vesicles were significantly larger than those where no contact was observed. These stellate cells formed local networks with adherent junctions observed at contact points. This study demonstrates that the villous stroma contains extracellular macrovesicles which are considerably larger than any previously described in tissue or plasma. The size and abundance of these macrovesicles in the villous stroma highlight the diversity of extracellular vesicle biology and their roles within connective tissues.
| S-EPMC6904625 | biostudies-literature
Project description:Background & objectivesDuring 6 to 8 wk of gestation, human placental villi show a complex pattern of morphogenesis. There is however, no large scale gene expression study exploring the temporal pattern of the developmental molecular networks in placental villi during the early weeks of gestation. We evaluated the transcriptome profiling of humn placental villus samples obtained from fertile women with voluntarily terminated normal pregnancies between 6-8 wk of gestation.MethodsTranscriptomic profiles of individual human placental villous samples from 25 women with normal pregnancies during 6 to 8 wk of gestation were examined using human whole genome expression arrays. Quantitative RT-PCR validation of copy numbers of transcripts for selected 15 genes and exploratory analysis of the microarray data revealed a high degree of quality assurance supportive of further clustering and differential analyses. Immunoblot and immunohistochemical analysis of selected five candidate proteins (CAGE1, CD9, SLC6A2, TANK and VEGFC) based on transcript profiles were done to assess the pattern of down stream informational flow.ResultsA large number (~9K) of genes with known functions were expressed in the experimental samples. The clustering analysis identified three major expression clusters with gestational age, and four co-expressional clusters. Differential analysis identified a highly discrete regulatory process involving only about 160 genes. Immunochemical analysis of selected candidate proteins based on transcript profiles revealed generally synchronous expression in human early placental villi.Interpretation & conclusionsSeveral signaling pathways linked to immunity (COL1, JAK2, JAK3, IL12, IL13, IL15, IL27, STAT3 and STAT5) were downregulated, while genes of the enriched category of antiviral immunity (ATF/AP1, IL10R and OAS) were clearly over-expressed. Transcriptional integration supportive of programmed development was observed in first trimester placental villi and it included regulation of apoptosis and cell cycle progression (ARRB1, ATR, BLM, CHRNA7, CHRNB1, FYN, KPNA4, and MTOR/FRAP), autophagy (ATG4B, ATG14, BAD, and BCL2), cell adhesion (CD9 and FN1) and epithelial-to-mesenchymal transition (CALD1, FN1, HEY1, MMP2, and WNT3A).
| S-EPMC3994729 | biostudies-literature
Project description:The placenta is the organ that mediates transport of nutrients and waste materials between mother and fetus. Synchrotron X-ray fluorescence (SXRF) microanalysis is a tool for imaging the distribution and quantity of elements in biological tissue, which can be used to study metal transport across biological membranes. Our aims were to pilot placental biopsy specimen preparation techniques that could be integrated into an ongoing epidemiology birth cohort study without harming rates of sample acquisition. We studied the effects of fixative (formalin or glutaraldehyde) and storage duration (30 days or immediate processing) on metal distribution and abundance and investigated a thaw-fixation protocol for archived specimens stored at -80 °C. We measured fixative elemental composition with and without a placental biopsy via inductively coupled plasma mass spectrometry (ICP-MS) to quantify fixative-induced elemental changes. Formalin-fixed specimens showed hemolysis of erythrocytes. The glutaraldehyde-paraformaldehyde solution in HEPES buffer (GTA-HEPES) had superior anatomical preservation, avoided hemolysis, and minimized elemental loss, although some cross-linking of exogenous Zn was evident. Elemental loss from tissue stored in fixative for 1 month showed variable losses (?40 % with GTA-HEPES), suggesting storage duration be controlled for. Thawing of tissue held at -80 °C in a GTA-HEPES solution provided high-quality visual images and elemental images.
| S-EPMC4663034 | biostudies-literature
Project description:BACKGROUND:Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) and cell-cell adhesion and trophoblast cells undergo changes in integrin expression as they differentiate. However, the mechanism(s) of integrin activation leading to integrin-mediated signaling in trophoblast cell differentiation is unknown. The Fermitin family proteins are integrin activators that help mediate integrin-mediated signaling, but have never been studied in detail within the human placenta. Thus, we examined the spatiotemporal pattern of expression of Fermitin family homolog-2 (FERMT2) in human chorionic villi throughout gestation and its role in trophoblast-substrate adhesion and invasion. METHODS:Placental villous tissue was obtained from patients undergoing elective terminations by dilatation and curettage at weeks 8-12 (n =?10), weeks 13-14 (n =?8), as well as from term deliveries at weeks 37-40 (n =?6). Tissues were fixed, processed and sections utilized for immunofluorescence analysis of FERMT2 expression during gestation. Additionally, HTR8-SVneo human trophoblast cells were transfected by electroporation with FERMT2-specific siRNAs or non-targeting siRNAs (control) and used in cell-substrate adhesion as well as invasion assays. RESULTS:FERMT2 was more commonly expressed in the basal domain of villous cytotrophoblast cells and prominently localized around the periphery of individual extravillous trophoblast cells. siRNA-mediated knockdown of FERMT2 in HTR8-SVneo cells resulted in significantly decreased trophoblast-substrate attachment (p <?0.05) as well as significantly decreased trophoblast invasion (p?<?0.05) relative to control cells. CONCLUSIONS:The detection of FERMT2 throughout extravillous trophoblast columns and the results of invasion assays demonstrated that this protein is likely an important regulator of integrin activation in extravillous cells to modulate migration and invasion.
| S-EPMC6211606 | biostudies-literature
Project description:Intra-amniotic (IA) inflammation is associated with significant morbidities for both the mother and the fetus. Prior studies have illustrated many of the effects of IA inflammation on the uterine lining (decidua) and membranous layers of the placenta at the fetal-maternal interface. However, much less is known about the immunological response occurring within the villous placenta. Using a rhesus macaque model of lipopolysaccharide (LPS)-induced IA inflammation, we showed that pregnancy-matched choriodecidua and villi have distinct immunological profiles in rhesus pregnancies. In the choriodecidua, we show that the abundance of neutrophils, multiple populations of antigen-presenting cells, and two populations of natural killer (NK) cells changes with prenatal IA LPS exposure. In contrast, in immune cells within the villous placenta we observed alterations in the abundance of B cells, monocytes, and CD8 T cells. Prior work has illustrated that IA inflammation leads to an increase in tumor necrosis factor alpha (TNF?) at the fetal-maternal interface. In this study, pretreatment with a TNF? blockade partially reversed inflammation in the placental villi. Furthermore, we report that immune cells in the villous placenta sensed LPS during our experimental window, and subsequently activated T cells to produce proinflammatory cytokines. Moreover, this study is the first report of memory T cells in third-trimester non-human primate placental villi and provides evidence that manipulation of immune cells in the villi at the fetal-maternal interface should be considered as a potential therapeutic target for IA inflammation.
| S-EPMC7256198 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) can influence the tumour microenvironment (TEM) and play a major role in tumourigenesis. Triple-negative [Ostrogen receptor (ER-), Progesterone receptor (PgR-), and HER2/neu receptor (HER2-)] breast cancer (TNBC) is an aggressive class of BC characterized by poor prognosis and lacks the benefit of routinely available targeted therapies. This study aims to investigate the effect of human placental chorionic villi derived MSCs (CVMSCs) on the behavior of TNBC in vitro. This was done by assaying different cancer hallmarks including proliferation, migration and angiogenesis. Cell proliferation rate of TNBC cell line (MDA-MB231) was monitored in real time using the xCELLigence system. Whereas, Boyden chamber migration assay was used to measure MDA-MB231 motility and invasiveness toward CVMSCs. Finally, a three-dimensional (3D) model using a co-culture system of CVMSCs with MDA-MB231 with or without the addition of human umbilical vein endothelial cells (HUVECs) was created to assess tumour angiogenesis in vitro. CVMSCs were able to significantly reduce the proliferative and migratory capacity of MDA-MB231 cells. Co-culturing of MDA-MB231 with CVMSCs, not only inhibited the tube formation ability of HUVECs but also reduced the expression of the BC characteristic cytokines; IL-10, IL-12, CXCL9 and CXCL10 of CVMSCs. These results support the hypothesis that CVMSCs can influence the behavior of TNBC cells and provides a basic for a potential therapeutic approach in a pre-clinical settings. The data from this study also highlight the complexity of the in vitro cancer angiogenesis model settings and regulations.
| S-EPMC6245746 | biostudies-literature
Project description:ObjectivesThe placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply) determines the fetal venous-arterial glucose difference (reflecting fetal consumption).MethodsCross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein) and outgoing vessels (uterine vein and umbilical artery).ResultsThere were significant mean (SD) uteroplacental arterio-venous 0.29 (0.23) mmol/L and fetal venous-arterial 0.38 (0.31) mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42) mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001), but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001) and the glucose concentration in the umbilical artery (r = -0.45, p = 0.004). Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001), but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values.ConclusionsWe did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly influenced by the fetal venous-arterial difference and not merely dependent on maternal glucose concentration or the arterio-venous difference on the maternal side of the placenta.
| S-EPMC4334523 | biostudies-literature
Project description:BACKGROUND: During human pregnancy, the placental villi produces high amounts of estradiol. This steroid is secreted by the syncytium, which is directly in contact with maternal blood. Estradiol has to cross placental foetal vessels to reach foetal circulation. The enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) was detected in placental endothelial cells of foetal vessels inside the villi. This enzyme catalyzes the conversion of estradiol to estrone, and of testosterone to androstenedione. It was proposed that estradiol level into foetal circulation could be regulated by 17beta-HSD2. METHODS: We obtained placentas from 10 to 26 6/7 weeks of pregnancy from women undergoing voluntary termination of pregnancy, term placentas were collected after normal spontaneous vaginal deliveries. We quantified 17beta-HSD2 mRNA levels in mid-gestation and term human placenta by RT-QPCR. We produced a new anti-17beta-HSD2 antibody to study its spatio-temporal expression by immunohistochemistry. We also compared steroid levels (testosterone, estrone and estradiol) and 17beta-HSD2 mRNA and protein levels between term placenta and endometrium. RESULTS: High 17beta-HSD2 mRNA and protein levels were found in both mid-gestation and term placentas. However, we showed that 17beta-HSD2 mRNA levels increase by 2.27 fold between mid-gestation and term. This period coincides with a transitional phase in the development of the villous vasculature. In mid-gestation placenta, high levels of 17beta-HSD2 were found in mesenchymal villi and immature intermediate villi, more precisely in endothelial cells of the stromal channel. At term, high levels of 17beta-HSD2 were found in the numerous sinusoidal capillaries of terminal villi. 17beta-HSD2 mRNA and protein levels in term placentas were respectively 25.4 fold and 30 to 60 fold higher than in the endometrium. Steroid levels were also significantly higher in term placenta than in the endometrium. CONCLUSION: The spatial and temporal expression of 17beta-HSD2 in the placenta during pregnancy and the comparison of 17beta-HSD2 expression and steroid levels between placental villi and endometrium are compatible with a role in the modulation of active and inactive forms of estrogens. Our observations strongly support the hypothesis that 17beta-HSD2 acts as a barrier decreasing estradiol secretion rates in the foetal circulation.
| S-EPMC1947994 | biostudies-literature