scholarly journals Dynamic remodeling of endometrial extracellular matrix regulates embryo receptivity in cattle

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 49-61 ◽  
Author(s):  
Saara Carollina Scolari ◽  
Guilherme Pugliesi ◽  
Ricardo de Francisco Strefezzi ◽  
Sónia Cristina da Silva Andrade ◽  
Luiz Lehmann Coutinho ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Pregnancy Outcome ◽  
Gene Ontology Analysis ◽  
Follicle Growth ◽  
Large Follicle ◽  
Ecm Remodeling ◽  
Expression Of Genes ◽  
Ovulatory Follicle ◽  
Key Genes ◽  
Small Follicle

We aimed to evaluate in the bovine endometrium whether (1) key genes involved in endometrial extracellular matrix (ECM) remodeling are regulated by the endocrine peri-ovulatory milieu and (2) specific endometrial ECM-related transcriptome can be linked to pregnancy outcome. In Experiment 1, pre-ovulatory follicle growth of cows was manipulated to obtain two groups with specific endocrine peri-ovulatory profiles: the Large Follicle-Large CL group (LF-LCL) served as a paradigm for greater receptivity and fertility and showed greater plasma pre-ovulatory estradiol and post-ovulatory progesterone concentrations compared to the Small Follicle-Small CL group (SF-SCL). Endometrium was collected on days 4 and 7 of the estrous cycle. Histology revealed a greater abundance of total collagen content in SF-SCL on day 4 endometrium. In Experiment 2, cows were artificially inseminated and, six days later, endometrial biopsies were collected. Cows were retrospectively divided into pregnant and non-pregnant (P vs NP) groups after diagnosis on day 30. In both experiments, expression of genes related to ECM remodeling in the endometrium was studied by RNAseq and qPCR. Gene ontology analysis showed an inhibition in the expression of ECM-related genes in the high receptivity groups (LF-LCL and P). Specifically, there was downregulation ofTGFB2,ADAMTS2,5 and 14,TIMP3 and COL1A2,COL3A1,COL7A1andCOL3A3in the LF-LCL and P groups. In summary, the overlapping set of genes differently expressed in both fertility models: (1) suggests that disregulation of ECM remodeling can impair receptivity and (2) can be used as markers to predict pregnancy outcome in cattle.

scholarly journals Steroidal Regulation of Oviductal microRNAs Is Associated with microRNA-Processing in Beef Cows

2021 ◽  
Vol 22 (2) ◽  
pp. 953
Author(s):  
Angela Maria Gonella-Diaza ◽  
Everton Lopes ◽  
Kauê Ribeiro da Silva ◽  
Ricardo Perecin Nociti ◽  
Gabriella Mamede Andrade ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Sex Steroids ◽  
Molecular Mechanisms ◽  
Beef Cows ◽  
Early Embryo ◽  
Preovulatory Follicle ◽  
Large Follicle ◽  
Specific Manner ◽  
Microrna Processing ◽  
Small Follicle

Information on molecular mechanisms through which sex-steroids regulate oviductal function to support early embryo development is lacking. Here, we hypothesized that the periovulatory endocrine milieu affects the miRNA processing machinery and miRNA expression in bovine oviductal tissues. Growth of the preovulatory follicle was controlled to obtain cows that ovulated a small follicle (SF) and subsequently bore a small corpus luteum (CL; SF-SCL) or a large follicle (LF) and large CL (LF-LCL). These groups differed in the periovulatory plasmatic sex-steroid’s concentrations. Ampulla and isthmus samples were collected on day four of the estrous cycle. Abundance of DROSHA, DICER1, and AGO4 transcripts was greater in the ampulla than the isthmus. In the ampulla, transcription of these genes was greater for the SF-SCL group, while the opposite was observed in the isthmus. The expression of the 88 most abundant miRNAs and 14 miRNAs in the ampulla and 34 miRNAs in isthmus were differentially expressed between LF-LCL and SF-SCL groups. Integration of transcriptomic and miRNA data and molecular pathways enrichment showed that important pathways were inhibited in the SF-SCL group due to miRNA control. In conclusion, the endocrine milieu affects the miRNA expression in the bovine oviduct in a region-specific manner.

scholarly journals Engineering cardiac microphysiological systems to model pathological extracellular matrix remodeling

2018 ◽  
Vol 315 (4) ◽  
pp. H771-H789 ◽  
Author(s):  
Nethika R. Ariyasinghe ◽  
Davi M. Lyra-Leite ◽  
Megan L. McCain
Keyword(s):  
Cardiovascular Disease ◽  
Extracellular Matrix ◽  
Myocardial Function ◽  
Myocardial Cell ◽  
Three Dimensions ◽  
Model Systems ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Microphysiological Systems

Many cardiovascular diseases are associated with pathological remodeling of the extracellular matrix (ECM) in the myocardium. ECM remodeling is a complex, multifactorial process that often contributes to declines in myocardial function and progression toward heart failure. However, the direct effects of the many forms of ECM remodeling on myocardial cell and tissue function remain elusive, in part because conventional model systems used to investigate these relationships lack robust experimental control over the ECM. To address these shortcomings, microphysiological systems are now being developed and implemented to establish direct relationships between distinct features in the ECM and myocardial function with unprecedented control and resolution in vitro. In this review, we will first highlight the most prominent characteristics of ECM remodeling in cardiovascular disease and describe how these features can be mimicked with synthetic and natural biomaterials that offer independent control over multiple ECM-related parameters, such as rigidity and composition. We will then detail innovative microfabrication techniques that enable precise regulation of cellular architecture in two and three dimensions. We will also describe new approaches for quantifying multiple aspects of myocardial function in vitro, such as contractility, action potential propagation, and metabolism. Together, these collective technologies implemented as cardiac microphysiological systems will continue to uncover important relationships between pathological ECM remodeling and myocardial cell and tissue function, leading to new fundamental insights into cardiovascular disease, improved human disease models, and novel therapeutic approaches.

scholarly journals Differential Requirement of DICER1 Activity during Development of Mitral and Tricuspid Valves

2022 ◽  
Author(s):  
Shun Yan ◽  
Yin Peng ◽  
Jin Lu ◽  
Saima Shakil ◽  
Yang Shi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tricuspid Valve ◽  
Regulatory Mechanisms ◽  
Mitral Valve Stenosis ◽  
Sequencing Analysis ◽  
Ecm Remodeling ◽  
Mitral Valves ◽  
Valve Development ◽  
Single Cell Rna Sequencing ◽  
Cell Sources

Mitral and tricuspid valves are essential for unidirectional blood flow in the heart. They are derived from similar cell sources, and yet congenital dysplasia affecting both valves is clinically rare, suggesting the presence of differential regulatory mechanisms underlying their development. We specifically inactivated Dicer1 in the endocardium during cardiogenesis, and unexpectedly found that Dicer1-deletion caused congenital mitral valve stenosis and regurgitation, while it had no impact on other valves. We showed that hyperplastic mitral valves were caused by abnormal condensation and extracellular matrix (ECM) remodeling. Our single-cell RNA Sequencing analysis revealed impaired maturation of mesenchymal cells and abnormal expression of ECM genes in mutant mitral valves. Furthermore, expression of a set of miRNAs that target ECM genes was significantly lower in tricuspid valves compared to mitral valves, consistent with the idea that the miRNAs are differentially required for mitral and tricuspid valve development. Our study thus reveals miRNA-mediated gene regulation as a novel molecular mechanism that differentially regulates mitral and tricuspid valve development, thereby enhancing our understanding of the non-association of inborn mitral and tricuspid dysplasia observed clinically.

scholarly journals Integrative analyses of biomarkers and pathways for heart failure

2021 ◽  
Author(s):  
Shaowei Fan ◽  
Yuanhui Hu
Keyword(s):  
Heart Failure ◽  
Extracellular Matrix ◽  
Microarray Data ◽  
Enrichment Analysis ◽  
Signal Pathway ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Pathway Enrichment Analysis ◽  
Ppi Networks ◽  
Key Genes

Abstract Background: Heart failure (HF) is the most common potential cause of death, causing a huge health and economic burden all over the world. So far, some impressive progress has been made in the study of pathogenesis. However, the underlying molecular mechanisms leading to this disease remain to be fully elucidated. Methods: The microarray data sets of GSE76701, GSE21610 and GSE8331 were retrieved from the gene expression comprehensive database (GEO). After merging all microarray data and adjusting batch effects, differentially expressed genes (DEG) were determined. Functional enrichment analysis was performed based on Gene Ontology (GO) resources, Kyoto Encyclopedia of Genes and Genomes (KEGG) resources, gene set enrichment analysis (GSEA), response pathway database and Disease Ontology (DO). Protein protein interaction (PPI) network was constructed using string database. Combined with the above important bioinformatics information, the potential key genes were selected. The comparative toxicological genomics database (CTD) is used to explore the interaction between potential key genes and HF. Results: We identified 38 patients with heart failure and 16 normal controls. There were 315 DEGs among HF samples, including 278 up-regulated genes and 37 down-regulated genes. Pathway enrichment analysis showed that most DEGs were significantly enriched in BMP signal pathway, transmembrane receptor protein serine / threonine kinase signal pathway, extracellular matrix, basement membrane, glycosaminoglycan binding, sulfur compound binding and so on. Similarly, GSEA enrichment analysis showed that DEGs were mainly enriched in extracellular matrix and extracellular matrix related proteins. BBS9, CHRD, BMP4, MYH6, NPPA and CCL5 are central genes in PPI networks and modules. Conclusions: the enrichment pathway of DEGs and go ontology may reveal the molecular mechanism of HF. Among them, target genes EIF1AY, RPS4Y1, USP9Y, KDM5D, DDX3Y, NPPA, HBB, TSIX, LOC28556 and XIST are expected to become new targets for heart failure. Our findings provide potential biomarkers or therapeutic targets for the further study of heart failure and contribute to the development of advanced prediction, diagnosis and treatment strategies.

scholarly journals Bone Mesenchymal Stem Cells Promote Extracellular Matrix Remodeling of Degenerated Nucleus Pulposus Cells via the miR-101-3p/EIF4G2 Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Zeng Wang ◽  
Xiaolin Ding ◽  
Feifei Cao ◽  
Xishan Zhang ◽  
Jingguo Wu
Keyword(s):  
Extracellular Matrix ◽  
Nucleus Pulposus ◽  
Quantitative Polymerase Chain Reaction ◽  
Matrix Remodeling ◽  
Nucleus Pulposus Cells ◽  
Promoting Effect ◽  
Bone Mesenchymal Stem Cells ◽  
Ecm Remodeling ◽  
Lumbar Vertebral Fracture ◽  
Related Proteins

The etiology of lumbocrural pain is tightly concerned with intervertebral disk degeneration (IDD). Bone mesenchymal stem cell (BMSC)-based therapy bears potentials for IDD treatment. The properties of microRNA (miRNA)-modified BMSCs may be altered. This study investigated the role and mechanism of BMSCs promoting extracellular matrix (ECM) remodeling of degenerated nucleus pulposus cells (NPCs) via the miR-101-3p/EIF4G2 axis. NPCs were collected from patients with IDD and lumbar vertebral fracture (LVF). The expressions of miR-101-3p and ECM-related proteins, Collagen-I (Col-I) and Collagen-II (Col-II), were detected using the reverse transcription-quantitative polymerase chain reaction. The expressions of Col-I and Col-II, major non-collagenous component Aggrecan, and major catabolic factor Matrix metalloproteinase-13 (MMP-13) were detected using Western blotting. BMSCs were cocultured with degenerated NPCs from patients with IDD. Viability and apoptosis of NPCs were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. After the degenerated NPCs were transfected with the miR-101-3p inhibitor, the expressions of ECM-related proteins, cell viability, and apoptosis were detected. The targeting relationship between miR-101-3p and EIF4G2 was verified. Functional rescue experiments verified the effects of miR-101-3p and EIF4G2 on ECM remodeling of NPCs. Compared with the NPCs of patients with LVF, the degenerated NPCs of patients with IDD showed downregulated miR-101-3p, Col-II, and Aggrecan expressions and upregulated MMP-13 and Col-I expressions. BMSCs increased the expressions of miR-101-3p, Aggrecan, and Col-II, and decreased the expressions of MMP-13 and Col-I in degenerated NPCs. BMSCs enhanced NPC viability and repressed apoptosis. Downregulation of miR-101-3p suppressed the promoting effect of BMSCs on ECM remodeling. miR-101-3p targeted EIF4G2. Downregulation of EIF4G2 reversed the inhibiting effect of the miR-101-3p inhibitor on ECM remodeling. In conclusion, BMSCs increased the miR-101-3p expression in degenerated NPCs to target EIF4G2, thus promoting the ECM remodeling of NPCs.

scholarly journals Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances

Sensors ◽  
2018 ◽  
Vol 18 (10) ◽  
pp. 3249 ◽  
Author(s):  
Hao Huang
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Surface Proteins ◽  
Biological Processes ◽  
Ecm Remodeling ◽  
Plasma Surface ◽  
Ecm Proteins ◽  
Recent Advances ◽  
Metalloproteinase 9

As one of the most widely investigated matrix metalloproteinases (MMPs), MMP-9 is a significant protease which plays vital roles in many biological processes. MMP-9 can cleave many extracellular matrix (ECM) proteins to regulate ECM remodeling. It can also cleave many plasma surface proteins to release them from the cell surface. MMP-9 has been widely found to relate to the pathology of cancers, including but not limited to invasion, metastasis and angiogenesis. Some recent research evaluated the value of MMP-9 as biomarkers to various specific cancers. Besides, recent research of MMP-9 biosensors discovered various novel MMP-9 biosensors to detect this enzyme. In this review, some recent advances in exploring MMP-9 as a biomarker in different cancers are summarized, and recent discoveries of novel MMP-9 biosensors are also presented.

scholarly journals Effect of large follicle puncture on IVF-ET outcome in patients with unsynchronized follicle maturationcan

2019 ◽  
Vol 47 (5) ◽  
pp. 2056-2066
Author(s):  
Xinrong Wang ◽  
Wenjuan Wang ◽  
Qinglan Qu ◽  
Ning Zhang ◽  
Cuifang Hao ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Pregnancy Outcomes ◽  
Endometrial Thickness ◽  
Multivariate Logistic Regression Analysis ◽  
Clinical Pregnancy ◽  
Control Group ◽  
Large Follicle ◽  
Vitro Fertilization ◽  
Follicular Maturation

Objective This retrospective study was conducted to explore causes of unsynchronized follicular maturation (UFM) and analyze the effects of large follicle puncture on embryo quality and pregnancy outcome. Methods Clinical features and controlled ovulation hyperstimulation (COH) were compared between the puncture group (n = 48) and the control group (n = 2545). We analyzed the COH process with in vitro fertilization during fresh cycle embryo transfer with different clinical pregnancy outcomes. We compared clinical characteristics and COH process of patients in the clinical pregnancy (n = 774) and non-clinical pregnancy (n = 527) groups. Finally, factors related to pregnancy outcomes were analyzed using multivariate logistic regression analysis. Results Age, level of estradiol on down-regulation day, and initial gonadotropin dose were significantly higher in the puncture group than in the control group. We detected significant differences in age, infertility, and body mass index (BMI) between the clinical and non-clinical pregnancy groups. Age, BMI, and endometrial thickness on the day of human chorionic gonadotropin administration were the independent factors influencing pregnancy outcome. Conclusions Patient’s age and level of anti-Müllerian hormone were the main factors causing UFM in patients undergoing COH. Large follicle puncture had no significant effect on pregnancy outcome.

scholarly journals Spatio-specific regulation of endocrine-responsive gene transcription by periovulatory endocrine profiles in the bovine reproductive tract

2016 ◽  
Vol 28 (10) ◽  
pp. 1533 ◽  
Author(s):  
Estela R. Araújo ◽  
Mariana Sponchiado ◽  
Guilherme Pugliesi ◽  
Veerle Van Hoeck ◽  
Fernando S. Mesquita ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reproductive Tract ◽  
Uterine Horn ◽  
Tissue Samples ◽  
Large Follicle ◽  
Endocrine Profiles ◽  
Peptidase Inhibitor ◽  
Solute Carrier ◽  
Specific Regulation ◽  
Small Follicle

In cattle, pro-oestrous oestradiol and dioestrous progesterone concentrations modulate endometrial gene expression and fertility. The aim was to compare the effects of different periovulatory endocrine profiles on the expression of progesterone receptor (PGR), oestrogen receptor 2 (ESR2), oxytocin receptor (OXTR), member C4 of aldo–keto reductase family 1 (AKR1C4), lipoprotein lipase (LPL), solute carrier family 2, member 1 (SLC2A1) and serpin peptidase inhibitor, clade A member 14 (SERPINA14): (1) between uterine horns ipsi- and contralateral to the corpus luteum (CL), (2) between regions of the ipsilateral horn and (3) in the vagina. Endometrium and vagina tissue samples were collected from cows that ovulated a larger (large follicle-large CL, LF-LCL; n = 6) or smaller follicle (small follicle-small CL, SF-SCL; n = 6) 7 days after oestrus. Cows in the LF-LCL group had a greater abundance of transcripts encoding ESR2, AKR1C4, LPL, SLC2A1 and SERPINA14, but a reduced expression of PGR and OXTR in the endometrium versus the SF-SCL group (P < 0.05). Expression of PGR and OXTR was greater in the contralateral compared with the ipsilateral horn (P < 0.05). Regardless of group, the anterior region of the ipsilateral horn had increased expression of PGR, ESR2, LPL, SLC2A1 and SERPINA14 (P < 0.05). Different periovulatory endocrine profiles, i.e. LF-LCL or SF-SCL, did not influence gene expression in the vagina and had no interaction with inter- or intra-uterine horn gene expression. In conclusion, inter- and intra-uterine horn variations in gene expression indicate that the expression of specific genes in the bovine reproductive tract is location dependent. However, spatial distribution of transcripts was not influenced by distinct periovulatory sex-steroid environments.

scholarly journals The Role of Changes in Extracellular Matrix of Cartilage in the Presence of Inflammation on the Pathology of Osteoarthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Maricela Maldonado ◽  
Jin Nam
Keyword(s):  
Extracellular Matrix ◽  
Repair Process ◽  
Cellular Component ◽  
Ecm Remodeling ◽  
Multiple Factors ◽  
Inflammatory Conditions ◽  
Composition And Structure ◽  
Poor Understanding ◽  
Wear And Tear

Osteoarthritis (OA) is a degenerative disease that affects various tissues surrounding joints such as articular cartilage, subchondral bone, synovial membrane, and ligaments. No therapy is currently available to completely prevent the initiation or progression of the disease partly due to poor understanding of the mechanisms of the disease pathology. Cartilage is the main tissue afflicted by OA, and chondrocytes, the sole cellular component in the tissue, actively participate in the degeneration process. Multiple factors affect the development and progression of OA including inflammation that is sustained during the progression of the disease and alteration in biomechanical conditions due to wear and tear or trauma in cartilage. During the progression of OA, extracellular matrix (ECM) of cartilage is actively remodeled by chondrocytes under inflammatory conditions. This alteration of ECM, in turn, changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. The changes in ECM composition and structure also prevent participation of mesenchymal stem cells in the repair process by inhibiting their chondrogenic differentiation. This review focuses on how inflammation-induced ECM remodeling disturbs cellular activities to prevent self-regeneration of cartilage in the pathology of OA.

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