scholarly journals MicroRNAs in Small Extracellular Vesicles Indicate Successful Embryo Implantation during Early Pregnancy

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 645 ◽  
Author(s):  
Qiang Tan ◽  
Shuang Shi ◽  
Jingjie Liang ◽  
Xiaowei Zhang ◽  
Dingren Cao ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Embryo Implantation ◽  
Extracellular Vesicle ◽  
Synchronous Communication ◽  
Normal Embryo ◽  
Multivesicular Bodies ◽  
Uterine Receptivity ◽  
Database Analysis ◽  
Mirna Expression Profiles ◽  
Future Practice

Synchronous communication between the developing embryo and the receptive endometrium is crucial for embryo implantation. Thus, uterine receptivity evaluation is vital in managing recurrent implantation failure (RIF). The potential roles of small extracellular vesicle (sEV) miRNAs in pregnancy have been widely studied. However, the systematic study of sEVs derived from endometrium and its cargos during the implantation stage have not yet been reported. In this study, we isolated endometrium-derived sEVs from the mouse endometrium on D2 (pre-receptive phase), D4 (receptive phase), and D5 (implantation) of pregnancy. Herein, we reveal that multivesicular bodies (MVBs) in the endometrium increase in number during the window of implantation (WOI). Moreover, our findings indicate that CD63, a well-known sEV marker, is expressed in the luminal and glandular epithelium of mouse endometrium. The sEV miRNA expression profiles indicated that miR-34c-5p, miR-210, miR-369-5p, miR-30b, and miR-582-5p are enriched during WOI. Further, we integrated the RIF’s database analysis results and found out that miR-34c-5p regulates growth arrest specific 1 (GAS1) for normal embryo implantation. Notably, miR-34c-5p is downregulated during implantation but upregulated in sEVs. An implication of this is the possibility that sEVs miR-34c-5p could be used to evaluate uterine states. In conclusion, these findings suggest that the endometrium derived-sEV miRNAs are potential biomarkers in determining the appropriate period for embryo implantation. This study also has several important implications for future practice, including therapy of infertility.

scholarly journals MicroRNAs in small extracellular vesicles indicate successful embryo implantation during early pregnancy

2020 ◽  
Author(s):  
Qiang Tan ◽  
Shuang Shi ◽  
Jingjie Liang ◽  
Xiaowei Zhang ◽  
Dingren Cao ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Early Stage ◽  
Expression Profiles ◽  
Embryo Implantation ◽  
Uterine Cavity ◽  
Synchronous Communication ◽  
Protein Markers ◽  
Uterine Receptivity ◽  
Transmission Electron ◽  
Mirnas Expression

Abstract Background : Synchronous communication between the developing embryo and the receptive endometrium is required for successful embryo implantation. Assessing of uterine receptivity is important for overcoming the recurrent implantation failure (RIF). Although the potential roles of small extracellular vesicles (sEVs) miRNAs in pregnancy have repeatedly mentioned, the systematic study of sEVs derived from endometrium and its cargoes during the implantation have not yet been reported. Methods : In this study, sEVs were isolated from mouse uterine cavity on D2 (pre-receptive phase), D4 (receptive phase) and D5 (implantation) of pregnancy using ultracentrifugation and analyzed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The miRNAs expression profiles of sEVs were identified by RT-qPCR. The datasets analysis of RIF were employed by an integrative bioinformatics analysis. The protein markers of sEVs were examined by western blotting. The effects of miRNAs in embryo implantation were determined by an agomir injection test. Results : Here we show that the number of multivesicular bodies (MVBs) in the endometrium is increased during the window of implantation (WOI). Meanwhile, the expression of CD63 is mainly located in the luminal and glandular epithelium. sEVs miRNAs profile reveal that miR-34c-5p, miR-210, miR-369-5p, miR-30b and miR-582-5p are enriched during WOI. By further integrating the database analysis results of RIF, we found that miR-34c-5p regulates GAS1 to involve normal process of embryo implantation. It is interesting that miR-34c-5p is down-regulated during implantation but enriched in sEVs. An implication of this is the possibility that sEVs miR-34c-5p could be used to evaluate uterine states. Conclusion : Our study identified that mouse endometrium release sEVs during the early stage of pregnancy, especially during WOI. We found that miR-34c-5p in sEVs affects embryo implantation by targeting to GAS1. Furthermore, the sEVs miRNAs suggest potential biomarkers for the choose of suitable period for embryo implantation. This study also has a number of important implications for future practice.

scholarly journals Differential MicroRNA Expression Involved in Endometrial Receptivity of Goats

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 472
Author(s):  
Xupeng Zang ◽  
Chen Zhou ◽  
Wenjing Wang ◽  
Jianyu Gan ◽  
Yaokun Li ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Expression Profiles ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Fish Analysis ◽  
Factors Affecting ◽  
Mirna Expression Profiles ◽  
Differentially Expressed Mirnas

Endometrial receptivity represents one of the leading factors affecting the successful implantation of embryos during early pregnancy. However, the mechanism of microRNAs (miRNAs) to establish goat endometrial receptivity remains unclear. This study was intended to identify potential miRNAs and regulatory mechanisms associated with establishing endometrial receptivity through integrating bioinformatics analysis and experimental verification. MiRNA expression profiles were obtained by high-throughput sequencing, resulting in the detection of 33 differentially expressed miRNAs (DEMs), followed by their validation through quantitative RT-PCR. Furthermore, 10 potential transcription factors (TFs) and 1316 target genes of these DEMs were obtained, and the TF–miRNA and miRNA–mRNA interaction networks were constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that these miRNAs were significantly linked to establishing endometrial receptivity. Moreover, the fluorescence in situ hybridization (FISH) analysis, dual-luciferase report assay, and immunohistochemistry (IHC) analysis corroborated that chi-miR-483 could directly bind to deltex E3 ubiquitin ligase 3L (DTX3L) to reduce its expression level. In conclusion, our findings contribute to a better understanding of molecular mechanisms regulating the endometrial receptivity of goats, and they provide a reference for improving embryo implantation efficiency.

scholarly journals Nuclear Shp2 directs normal embryo implantation via facilitating the ERα tyrosine phosphorylation by the Src kinase

2017 ◽  
Vol 114 (18) ◽  
pp. 4816-4821 ◽  
Author(s):  
Hao Ran ◽  
Shuangbo Kong ◽  
Shuang Zhang ◽  
Jianghong Cheng ◽  
Chan Zhou ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Tyrosine Phosphatase ◽  
Embryo Implantation ◽  
Src Kinase ◽  
Estrogen Receptor Α ◽  
Normal Embryo ◽  
Uterine Receptivity ◽  
Mouse Uterus ◽  
Independent Manner ◽  
Rtk Signaling

Estrogen and progesterone coupled with locally produced signaling molecules are essential for embryo implantation. However, the hierarchical landscape of the molecular pathways that governs this process remains largely unexplored. Here we show that the protein tyrosine phosphatase Shp2, a positive transducer of RTK signaling, is predominately localized in the nuclei in the periimplantation mouse uterus. Uterine-specific deletion of Shp2 exhibits reduced progesterone receptor (PR) expression and progesterone resistance, which derails normal uterine receptivity, leading to complete implantation failure in mice. Notably, the PR expression defects are attributed to the limited estrogen receptor α (ERα) activation in uterine stroma. Further analysis reveals that nuclear Shp2, rather than cytosolic Shp2, promotes the ERα transcription activity. This function is achieved by enhancing the Src kinase-mediated ERα tyrosine phosphorylation, which facilitates ERα binding to Pgr promoter in an ERK-independent manner in periimplantation uteri. Besides uncovering a regulatory mechanism, this study could be clinically relevant to dysfunctional ERα-caused endometrial disorders in women.

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

scholarly journals miRNA expression profiles in liver grafts of HCV and HIV/HCV infected recipients, six months after liver transplantation

2021 ◽  
Author(s):  
Michela Bulfoni ◽  
Riccardo Pravisani ◽  
Emiliano Dalla ◽  
Daniela Cesselli ◽  
Masaaki Hidaka ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Mirna Expression Profiles

scholarly journals MicroRNA expression classification for pediatric multiple sclerosis identification

2021 ◽  
Author(s):  
Gabriella Casalino ◽  
Giovanna Castellano ◽  
Arianna Consiglio ◽  
Nicoletta Nuzziello ◽  
Gennaro Vessio
Keyword(s):  
Machine Learning ◽  
Multiple Sclerosis ◽  
Expression Profiles ◽  
Healthy Children ◽  
Multifactorial Diseases ◽  
Hyperactivity Disorder ◽  
Pediatric Multiple Sclerosis ◽  
Mirna Expression Profiles ◽  
Selection Algorithms ◽  
Expression Classification

Abstract MicroRNAs (miRNAs) are a set of short non-coding RNAs that play significant regulatory roles in cells. The study of miRNA data produced by Next-Generation Sequencing techniques can be of valid help for the analysis of multifactorial diseases, such as Multiple Sclerosis (MS). Although extensive studies have been conducted on young adults affected by MS, very little work has been done to investigate the pathogenic mechanisms in pediatric patients, and none from a machine learning perspective. In this work, we report the experimental results of a classification study aimed at evaluating the effectiveness of machine learning methods in automatically distinguishing pediatric MS from healthy children, based on their miRNA expression profiles. Additionally, since Attention Deficit Hyperactivity Disorder (ADHD) shares some cognitive impairments with pediatric MS, we also included patients affected by ADHD in our study. Encouraging results were obtained with an artificial neural network model based on a set of features automatically selected by feature selection algorithms. The results obtained show that models developed on automatically selected features overcome models based on a set of features selected by human experts. Developing an automatic predictive model can support clinicians in early MS diagnosis and provide new insights that can help find novel molecular pathways involved in MS disease.

Effects of the Co‐Administration of MK‐801 and Clozapine MiRNA Expression Profiles in Rats

2021 ◽  
Author(s):  
Wenhui Huang ◽  
Xuefeng Gu ◽  
Yingying Wang ◽  
Yuhan Bi ◽  
Yu. Yang ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Mk 801 ◽  
Mirna Expression Profiles

scholarly journals Heparan Sulfate Proteoglycan Sulfation Regulates Uterine Differentiation and Signaling During Embryo Implantation

Endocrinology ◽  
2018 ◽  
Vol 159 (6) ◽  
pp. 2459-2472 ◽  
Author(s):  
Yan Yin ◽  
Adam Wang ◽  
Li Feng ◽  
Yu Wang ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Heparan Sulfate ◽  
Signaling Pathways ◽  
Reproductive Tract ◽  
Ovarian Function ◽  
Embryo Implantation ◽  
Uterine Epithelium ◽  
Female Reproductive Tract ◽  
Uterine Receptivity ◽  
Mouse Uterus

Abstract To prepare for embryo implantation, the uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs). HSPGs play crucial roles in signal transduction by regulating morphogen transport and ligand binding. In this study, we examine the role of HSPG sulfation in regulating uterine receptivity by conditionally deleting the N-deacetylase/N-sulfotransferase (NDST) 1 gene (Ndst1) in the mouse uterus using the Pgr-Cre driver, on an Ndst2- and Ndst3-null genetic background. Although development of the female reproductive tract and subsequent ovarian function appear normal in Ndst triple-knockout females, they are infertile due to implantation defects. Embryo attachment appears to occur but the uterine epithelium at the site of implantation persists rather than disintegrates in the mutant. Uterine epithelial cells continued to proliferate past day 4 of pregnancy, accompanied by elevated Fgf2 and Fgf9 expression, whereas uterine stroma failed to undergo decidualization, as evidenced by lack of Bmp2 induction. Despite normal Indian hedgehog expression, transcripts of Ptch1 and Gli1, both components as well as targets of the hedgehog (Hh) pathway, were detected only in the subepithelial stroma, indicating altered Hh signaling in the mutant uterus. Taken together, these data implicate an essential role for HSPGs in modulating signal transduction during mouse implantation.

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