Three-dimensional understanding of the morphological complexity of the human uterine endometrium.
Ontology highlight
ABSTRACT:
SUBMITTER: Yamaguchi M
PROVIDER: S-EPMC7995615 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The histology of the endometrium has traditionally been established by observation of two-dimensional (2D) pathological sections. However, because human endometrial glands exhibit coiling and branching morphology, it is extremely difficult to obtain an entire image of the glands by 2D observation. In recent years, the development of three-dimensional (3D) reconstruction of serial pathological sections by computer and whole-mount imaging technology using tissue clearing methods with high-resolution fluorescence microscopy has enabled us to observe the 3D histoarchitecture of tissues. As a result, 3D imaging has revealed that human endometrial glands form a plexus network in the basalis, similar to the rhizome of grass, whereas mouse uterine glands are single branched tubular glands. This review summarizes the relevant literature on the 3D structure of mouse and human endometrium and discusses the significance of the rhizome structure in the human endometrium and the expected role of understanding the 3D tissue structure in future applications to systems biology.
| S-EPMC8401133 | biostudies-literature
Project description:Study questionCan we reconstitute physiologically relevant 3-dimensional (3D) microengineered endometrium in-vitro model?Summary answerOur representative microengineered vascularised endometrium on-a-chip closely recapitulates the endometrial microenvironment that consists of three distinct layers including epithelial cells, stromal fibroblasts and endothelial cells in a 3D extracellular matrix in a spatiotemporal manner.What is known alreadyOrgan-on-a-chip, a multi-channel 3D microfluidic cell culture system, is widely used to investigate physiologically relevant responses of organ systems.Study design, size, durationThe device consists of five microchannels that are arrayed in parallel and partitioned by array of micropost. Two central channels are for 3D culture and morphogenesis of stromal fibroblast and endothelial cells. In addition, the outermost channel is for the culture of additional endometrial stromal fibroblasts that secrete biochemical cues to induce directional pro-angiogenic responses of endothelial cells. To seed endometrial epithelial cells, on Day 8, Ishikawa cells were introduced to one of the two medium channels to adhere on the gel surface. After that, the microengineered endometrium was cultured for an additional 5-6 days (total ∼ 14 days) for the purpose of each experiment.Participants/materials, setting, methodsMicrofluidic 3D cultures were maintained in endothelial growth Medium 2 with or without oestradiol and progesterone. Some cultures additionally received exogenous pro-angiogenic factors. For the three distinct layers of microengineered endometrium-on-a-chip, the epithelium, stroma and blood vessel characteristics and drug response of each distinct layer in the microfluidic model were assessed morphologically and biochemically. The quantitative measurement of endometrial drug delivery was evaluated by the permeability coefficients.Main results and the role of chanceWe established microengineered vascularised endometrium-on-chip, which consists of three distinct layers: epithelium, stroma and blood vessels. Our endometrium model faithfully recapitulates in-vivo endometrial vasculo-angiogenesis and hormonal responses displaying key features of the proliferative and secretory phases of the menstrual cycle. Furthermore, the effect of the emergency contraception drug levonorgestrel was evaluated in our model demonstrating increased endometrial permeability and blood vessel regression in a dose-dependent manner. We finally provided a proof of concept of the multi-layered endometrium model for embryo implantation, which aids a better understanding of the molecular and cellular mechanisms underlying this process.Large scale dataN/A.Limitations, reasons for cautionThis report is largely an in-vitro study and it would be beneficial to validate our findings using human primary endometrial cells.Wider implications of the findingsOur 3D microengineered vascularised endometrium-on-a-chip provides a new in-vitro approach to drug screening and drug discovery by mimicking the complicated behaviours of human endometrium. Thus, we suggest our model as a tool for addressing critical challenges and unsolved problems in female diseases, such as endometriosis, uterine cancer and female infertility, in a personalised manner.Study funding/competing interest(s)This work is supported by funding from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) to Y.J.K. (No. 2018R1C1B6003), to J.A. (No. 2020R1I1A1A01074136) and to H.S.K. (No. 2020R1C1C100787212). The authors report no conflicts of interest.
| S-EPMC8450871 | biostudies-literature
Project description:Study questionCan primary human uterine microvascular endothelial cells (UtMVECs) be used as a model to study uterine angiogenic responses in vitro that are relevant in pregnancy?Summary answerUtMVECs demonstrated angiogenic responses when stimulated with proangiogenic factors, including sphingosine 1-phosphate (S1P), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), physiological levels of wall shear stress (WSS), human chorionic gonadotropin (hCG) and various combinations of estrogen and progesterone.What is known alreadyDuring sprouting angiogenesis, signaling from growth factors and cytokines induces a monolayer of quiescent endothelial cells (ECs) lining the vasculature to degrade the extracellular matrix and invade the surrounding tissue to form new capillaries. During pregnancy and the female reproductive cycle, the uterine endothelium becomes activated and undergoes sprouting angiogenesis to increase the size and number of blood vessels in the endometrium.Study design, size, durationThe study was designed to examine the angiogenic potential of primary human UtMVECs using the well-characterized human umbilical vein EC (HUVEC) line as a control to compare angiogenic potential. ECs were seeded onto three-dimensional (3D) collagen matrices, supplemented with known proangiogenic stimuli relevant to pregnancy and allowed to invade for 24 h. Sprouting responses were analyzed using manual and automated methods for quantification.Participants/materials, setting, methodsRT-PCR, Western blot analysis and immunostaining were used to characterize UtMVECs. Angiogenic responses were examined using 3D invasion assays. Western blotting was used to confirm signaling responses after proangiogenic lipid, pharmacological inhibitor, and recombinant lentiviral treatments. All experiments were repeated at least three times.Main results and the role of chanceAfter ensuring that UtMVECs expressed the proper endothelial markers, we found that UtMVECs invade 3D collagen matrices dose-dependently in response to known proangiogenic stimuli (e.g. S1P, VEGF, bFGF, hCG, estrogen, progesterone and WSS) present during early pregnancy. Invasion responses were positively correlated with phosphorylation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and p42/p44 mitogen-activated protein kinase (ERK). Inhibition of these second messengers significantly impaired sprouting (P < 0.01). Gene silencing of membrane type 1-matrix metalloproteinase using multiple approaches completely abrogated sprouting (P < 0.001). Finally, UtMVECs displayed a unique ability to undergo sprouting in response to hCG, and combined estrogen and progesterone treatment.Large scale dataNot applicable.Limitations, reasons for cautionThe study of uterine angiogenesis in vitro has limitations and any findings many not fully represent the in vivo state. However, these experiments do provide evidence for the ability of UtMVECs to be used in functional sprouting assays in a 3D environment, stimulated by physiological factors that are produced locally within the uterus during early pregnancy.Wider implications of the findingsWe show that UtMVECs can be used reliably to investigate how growth factors, hormones, lipids and other factors, such as flow, affect angiogenesis in the uterus.Study funding/competing interestsThis work was supported by NIH award HL095786 to K.J.B. The authors have no conflicts of interest.
| S-EPMC6454809 | biostudies-literature
Project description:2D macromolecules, such as graphene and graphene oxide, possess a rich spectrum of conformational phases. However, their morphological classification has only been discussed by visual inspection, where the physics of deformation and surface contact cannot be resolved. We employ machine learning methods to address this problem by exploring samples generated by molecular simulations. Features such as metric changes, curvature, conformational anisotropy and surface contact are extracted. Unsupervised learning classifies the morphologies into the quasi-flat, folded, crumpled phases and interphases using geometrical and topological labels or the principal features of the 2D energy map. The results are fed into subsequent supervised learning for phase characterization. The performance of data-driven models is improved notably by integrating the physics of geometrical deformation and topological contact. The classification and feature extraction characterize the microstructures of their condensed phases and the molecular processes of adsorption and transport, comprehending the processing-microstructures-performance relation in applications.
| S-EPMC9214330 | biostudies-literature
Project description:Conventional education results in unsatisfactory morphological understanding of acetabular fractures due to lack of three-dimensional (3D) details and tactile feedback of real fractures. Virtual reality (VR) and 3D printing (3DP) techniques are widely applied in teaching. The purpose of this study was to identify the effect of physical model (PM), VR and 3DP models in education of morphological understanding of acetabular fractures. 141 students were invited to participate in this study. Participants were equally and randomly assigned to the PM, VR and 3DP learning groups. Three-level objective tests were conducted to evaluate learning, including identifying anatomical landmarks, describing fracture lines, identifying classification, and inferring fracture mechanism. Four subjective questions were asked to evaluate the usability and value of instructional materials. Generally, the 3DP group showed a clear advantage over the PM and VR groups in objective tests, while there was no significant difference between the PM and VR groups. 3DP was considered to be the most valuable learning tool for understanding acetabular fractures. The findings demonstrate that 3DP modelling of real fractures is an effective learning instrument that can be used to understand the morphology of acetabular fractures and promote subjective interest.
| S-EPMC5771611 | biostudies-literature
Project description:Many captive animals are fed diets that are drastically different in mechanical properties than their wild diet. Most captive pantherines are fed a nutritionally supplemented diet consisting almost entirely of ground meat. While many zoos supplement this diet with bones, the fact remains that large captive felids are fed diets that require substantially less masticatory effort than those of their wild counterparts. The osteological effects of this dietary difference have not been fully evaluated. To this end, we compared linear measurements and 3D geometric morphometric landmarks of captive and wild lions and tigers. Using Principal Component (PC) analysis of the linear measurements, not only were the sexes and species statistically distinct, but so too was the population clearly divisible in terms of captivity status. The 3D analysis supported these findings: although the most influential variable in the sample (PC1, 21.5% of the variation) separates the two species, the second most influential contributor (PC2) to the overall skull shape is driven not by the sex differences in these highly dimorphic species, but rather by their captivity status. In fact, captivity status drives nearly twice as much of the 3D variation as sexual dimorphism (14.8% vs. 8.0% for PC2 vs. PC3). Thus the shape is influenced nearly twice as much by whether the animal was captive or wild than by whether it was male or female. If a causal relationship can be demonstrated between dietary mechanical properties and morphology, people who oversee the diets of captive carnivores should consider modifying these diets to account for not only nutritional but also the mechanical properties of a carcass-based diet as well. In addition to the husbandry implications, our analyses show the ways in which captive specimens are different than their wild counterparts--ndings that have implications for morphologists when considering anatomical samples.
| S-EPMC4237414 | biostudies-literature
Project description:We aim to provide an overview of the various digital three-dimensional visualizations used for learning anatomy and to assess whether these improve medical students' understanding of anatomy compared to traditional learning methods. Furthermore, we evaluate the attitudes of the users of three-dimensional visualizations. We included articles that compared advanced newer three-dimensional anatomy visualization methods (i.e., virtual reality, augmented reality, and computer-based three-dimensional visualizations) to traditional methods that have been used for a long time (i.e., cadaver and textbooks) with regard to users' understanding of anatomy. Of the 1,148 articles identified, 21 articles reported data on the effectiveness of using three-dimensional visualization methods compared to two-dimensional methods. Twelve articles found that three-dimensional visualization is a significantly more effective learning method compared to traditional methods, whereas nine articles did not find that three-dimensional visualization was a significantly more effective method. In general, based on these articles, medical students prefer to use three-dimensional visualizations to learn anatomy. In most of the articles, using three-dimensional visualization was shown to be a more effective method to gain anatomical knowledge compared to traditional methods. Besides that, students are motivated and interested in using these new visualization methods for learning anatomical structures. Clin. Anat. 32:25-33, 2019. © 2019 Wiley Periodicals, Inc.
| S-EPMC6916638 | biostudies-literature
Project description:BACKGROUND:The words 'infection' and 'inflammation' lack specific definitions. Here, such words are not defined. Instead, the ability to visualize host-microbial interactions was explored. METHODS:Leukocyte differential counts and four bacterial species (Staphylococcus aureus, Streptococcus dysgalactiae, Staphylococcus chromogenes, and Escherichia coli) were determined or isolated in a cross-sectional and randomized study conducted with 611 bovine milk samples. Two paradigms were evaluated: (i) the classic one, which measures non-structured (count or percent) data; and (ii) a method that, using complex data structures, detects and differentiates three-dimensional (3D) interactions among lymphocytes (L), macrophages (M), and neutrophils (N). RESULTS:Classic analyses failed to differentiate bacterial-positive (B+) from -negative (B-) observations: B- and B+ data overlapped, even when statistical significance was achieved. In contrast, the alternative approach showed distinct patterns, such as perpendicular data inflections, which discriminated microbial-negative/mononuclear cell-predominating (MCP) from microbial-positive/phagocyte-predominating (PP) subsets. Two PP subcategories were distinguished, as well as PP/culture-negative (false-negative) and MCP/culture-positive (false-positive) observations. In 3D space, MCP and PP subsets were perpendicular to one another, displaying ? 91% specificity or sensitivity. Findings supported five inferences: (i) disease is not always ruled out by negative bacterial tests; (ii) low total cell counts can coexist with high phagocyte percents; (iii) neither positive bacterial isolation nor high cell counts always coincide with PP profiles; (iv) statistical significance is not synonymous with discrimination; and (v) hidden relationships cannot be detected when simple (non-structured) data formats are used and statistical analyses are performed before data subsets are identified, but can be uncovered when complexity is investigated. CONCLUSIONS:Pattern recognition-based assessments can detect host-microbial interactions usually unobserved. Such cutoff-free, confidence interval-free, gold standard-free approaches provide interpretable information on complex entities, such as 'infection' and 'inflammation', even without definitions. To investigate disease dynamics, combinations of observational and experimental longitudinal studies, on human and non-human infections, are recommended.
| S-EPMC4397090 | biostudies-literature
Project description:Bovine in vitro endometrial models that resemble tissue function in vivo are needed to study infertility, long-term uterine alterations induced by pathogens and impact of endocrine disruptor chemicals on reproductive function and other reproductive system complications that cause high economic losses in livestock species. The present study aimed to generate an innovative, reproducible, and functional 3D scaffold-based model of the bovine endometrium structurally robust for long term-culture. We developed a multicellular model containing both endometrial epithelial and stromal cells. Epithelial cells organized to form a luminal-like epithelial layer on the surface of the scaffold. Stromal cells produced their own extracellular matrix forming a stable subepithelial compartment that physiologically resembles the normal endometrium. Both cell types released prostaglandin E2 and prostaglandin F2α following a treatment with oxytocin and arachidonic acid. Additionally signal pathways mediating oxytocin and arachidonic acid stimulation of prostaglandin synthesis were analyzed by real time PCR (RT-PCR). Oxytocin receptor (OXTR), prostaglandin E2 receptor 2 (EP2), prostaglandin E2 receptor 4 (EP4), prostaglandin F receptor (PTGFR), prostaglandin E synthase (PTGES), PGF-synthase (PGFS) and prostaglandin-endoperoxide synthase 2 (COX-2) expression was detected in both control and treatment groups, however, only significant changes in abundance of OXTR mRNA transcripts were found. The results obtained by this study are a step forward in bovine in vitro culture technology. This 3D scaffold-based model provides a platform to study regulatory mechanisms involved in endometrial physiology and can set the basis for a broader tool for designing and testing novel therapeutic strategies for recurrent uterine pathologies.
| S-EPMC10484811 | biostudies-literature
Project description:The three-dimensional (3D) organization of chromatin in the nucleus of diploid eukaryotic organisms has fascinated biologists for many years. Despite major progress in chromatin conformation studies, current knowledge regarding the spatial organization of diploid (maternal and paternal) genomes is still limited. Recent advances in Hi-C technology and data processing approaches have enabled construction of diploid Hi-C contact maps. These maps greatly accelerated the pace of novel discoveries in haplotype-resolved 3D genome studies, revealing the role of allele biased chromatin conformation in transcriptional regulation. Here, we review emerging concepts and haplotype phasing strategies of Hi-C data in 3D diploid genome studies. We discuss new insights on homologous chromosomal organization and the interplay between allelic biased chromatin architecture and several nuclear functions, explaining how haplotype-resolved Hi-C technologies have been used to resolve important biological questions.
| S-EPMC8246089 | biostudies-literature