Extracellular vesicle research in reproductive science— Paving the way for clinical achievements

2022 ◽  
Author(s):  
Elina Aleksejeva ◽  
Natasa Zarovni ◽  
Keerthie Dissanayake ◽  
Kasun Godakumara ◽  
Paola Vigano ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Early Embryo ◽  
Clinical Settings ◽  
Menstrual Phase ◽  
Standardized Measurement ◽  
Reproductive Science ◽  
Mediate Cell ◽  
Therapeutic Art

Abstract Mammalian conception involves a multitude of reciprocal interactions via a molecular dialogue between mother and conceptus. Extracellular vesicles (EVs) are secreted membrane-encapsulated particles that mediate cell-to-cell communication in various contexts. EVs, which are present in seminal, follicular, oviductal, and endometrial fluids, as well as in embryo secretions, carry molecular constituents that impact gamete maturation, fertilization, early embryo development, and embryo-maternal communication. The distribution, concentration, and molecular cargo of EVs are regulated by steroid hormones and the health status of the tissue of origin, and thus are influenced by menstrual phase, stage of conception, and the presence of infertility-associated diseases. EVs have been recognized as a novel source of biomarkers and potential reproductive medicine therapeutics, particularly for assisted reproductive technology (ART). There are still many technological and scientific hindrances to be overcome before EVs can be used in clinical diagnostic and therapeutic ART applications. Issues to be resolved include the lack of standardized measurement protocols and an absence of absolute EV quantification technologies. Additionally, clinically suitable and robust EV isolation methods have yet to be developed. In this review, we provide an overview of EV-mediated interactions during the early stages of reproduction from gamete maturation to embryo implantation and then outline the technological progress that must be made for EV applications to be translated to clinical settings.

scholarly journals The Biological Function of Extracellular Vesicles during Fertilization, Early Embryo—Maternal Crosstalk and Their Involvement in Reproduction: Review and Overview

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1510
Author(s):  
Emanuele Capra ◽  
Anna Lange-Consiglio
Keyword(s):  
Extracellular Vesicles ◽  
Spatial Interaction ◽  
Cell Communication ◽  
Early Embryo ◽  
Molecular Profile ◽  
Cell Of Origin ◽  
Non Invasive ◽  
Temporal And Spatial ◽  
Mediate Cell

Secretory extracellular vesicles (EVs) are membrane-enclosed microparticles that mediate cell to cell communication in proximity to, or distant from, the cell of origin. Cells release a heterogeneous spectrum of EVs depending on their physiologic and metabolic state. Extracellular vesicles are generally classified as either exosomes or microvesicles depending on their size and biogenesis. Extracellular vesicles mediate temporal and spatial interaction during many events in sexual reproduction and supporting embryo-maternal dialogue. Although many omic technologies provide detailed understanding of the molecular cargo of EVs, the difficulty in obtaining populations of homogeneous EVs makes difficult to interpret the molecular profile of the molecules derived from a miscellaneous EV population. Notwithstanding, molecular characterization of EVs isolated in physiological and pathological conditions may increase our understanding of reproductive and obstetric diseases and assist the search for potential non-invasive biomarkers. Moreover, a more precise vision of the cocktail of biomolecules inside the EVs mediating communication between the embryo and mother could provide new insights to optimize the therapeutic action and safety of EV use.

CSF extracellular vesicles and risk of disease activity after a first demyelinating event

2021 ◽  
pp. 135245852098754
Author(s):  
Gloria Dalla Costa ◽  
Tommaso Croese ◽  
Marco Pisa ◽  
Annamaria Finardi ◽  
Lorena Fabbella ◽  
...  
Keyword(s):  
Disease Activity ◽  
Extracellular Vesicles ◽  
Prognostic Markers ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Intervention Strategies ◽  
Targeted Intervention ◽  
Improve Risk Stratification ◽  
Risk Of Disease ◽  
In Cis

Background: Extracellular vesicles (EVs), a recently described mechanism of cell communication, are released from activated microglial cells and macrophages and are a candidate biomarker in diseases characterized by chronic inflammatory process such as multiple sclerosis (MS). Methods: We explored cerebrospinal fluid extracellular vesicle (CSF EV) of myeloid origin (MEVs), cytokine and chemokine levels in patients with clinically isolated syndrome (CIS). Results: We found that CSF MEVs were significantly higher in CIS patients than in controls and were inversely correlated to CSF CCL2 levels. MEVs level were significantly associated with an shorter time to evidence of disease activity (hazard ratio: 1.01, 95% confidence interval: 1.00–1.02, p < 0.01) independently from other known prognostic markers. Conclusion: After a first demyelinating event, CSF EVs may improve risk stratification of these patients and allow more targeted intervention strategies.

scholarly journals Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3827
Author(s):  
Jae Young Hur ◽  
Kye Young Lee
Keyword(s):  
Therapeutic Potential ◽  
Extracellular Vesicle ◽  
Clinical Settings ◽  
Biomarker Detection ◽  
Diagnosis And Prognosis ◽  
Double Stranded Dna ◽  
Fundamental Research ◽  
The Stability ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Extracellular vesicles (EVs) carry RNA, proteins, lipids, and diverse biomolecules for intercellular communication. Recent studies have reported that EVs contain double-stranded DNA (dsDNA) and oncogenic mutant DNA. The advantage of EV-derived DNA (EV DNA) over cell-free DNA (cfDNA) is the stability achieved through the encapsulation in the lipid bilayer of EVs, which protects EV DNA from degradation by external factors. The existence of DNA and its stability make EVs a useful source of biomarkers. However, fundamental research on EV DNA remains limited, and many aspects of EV DNA are poorly understood. This review examines the known characteristics of EV DNA, biogenesis of DNA-containing EVs, methylation, and next-generation sequencing (NGS) analysis using EV DNA for biomarker detection. On the basis of this knowledge, this review explores how EV DNA can be incorporated into diagnosis and prognosis in clinical settings, as well as gene transfer of EV DNA and its therapeutic potential.

scholarly journals Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis

2021 ◽  
Vol 22 (10) ◽  
pp. 5177
Author(s):  
Yi Yang ◽  
Jia-Peng He ◽  
Ji-Long Liu
Keyword(s):  
Single Cell ◽  
Molecular Mechanism ◽  
Single Cell Analysis ◽  
Embryo Implantation ◽  
Cell Communication ◽  
Human Reproduction ◽  
Mouse Uterus ◽  
Implantation Sites ◽  
Low Efficiency ◽  
Signaling Interactions

As a crucial step for human reproduction, embryo implantation is a low-efficiency process. Despite rapid advances in recent years, the molecular mechanism underlying embryo implantation remains poorly understood. Here, we used the mouse as an animal model and generated a single-cell transcriptomic atlas of embryo implantation sites. By analyzing inter-implantation sites of the uterus as control, we were able to identify global gene expression changes associated with embryo implantation in each cell type. Additionally, we predicted signaling interactions between uterine luminal epithelial cells and mural trophectoderm of blastocysts, which represent the key mechanism of embryo implantation. We also predicted signaling interactions between uterine epithelial-stromal crosstalk at implantation sites, which are crucial for post-implantation development. Our data provide a valuable resource for deciphering the molecular mechanism underlying embryo implantation.

scholarly journals Anterior Gradient Protein 3 and S100 Calcium-Binding Protein P Levels in Different Endometrial Epithelial Compartments May Play an Important Role in Recurrent Pregnancy Failure

2021 ◽  
Vol 22 (8) ◽  
pp. 3835
Author(s):  
Nicola Tempest ◽  
Elizabeth Batchelor ◽  
Christopher J. Hill ◽  
Hannan Al-Lamee ◽  
Josephine Drury ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Binding Protein ◽  
Embryo Implantation ◽  
Calcium Signalling ◽  
Premenopausal Women ◽  
Subcellular Location ◽  
Early Embryo ◽  
Calcium Binding Protein ◽  
Regulatory Function ◽  
S100 Calcium Binding Protein

Recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) are distressing conditions without effective treatments. The luminal epithelium (LE) is integral in determining receptivity of the endometrium, whereas functionalis glands and stroma aid in nurturing early embryo development. Calcium signalling pathways are known to be of vital importance to embryo implantation and pregnancy establishment, and anterior gradient protein 3 (AGR3) and S100 calcium-binding protein P (S100P) are involved with these pathways. We initially examined 20 full-thickness endometrial biopsies from premenopausal women across the menstrual cycle to characterize levels of AGR3 protein in each endometrial sub-region at the cellular level. A further 53 endometrial pipelle biopsies collected in the window of implantation were subsequently assessed to determine differential endometrial AGR3 and S100P levels relevant to RIF (n = 13) and RPL (n = 10) in comparison with parous women (n = 30) using immunohistochemistry. Significantly higher AGR3 and S100P immunostaining was observed in ciliated cells of the LE of women with recurrent reproductive failure compared with parous women, suggesting aberrant subcellular location-associated pathophysiology for these conditions. The nuclear localisation of S100P may allow transcriptional regulatory function, which is necessary for implantation of a viable pregnancy. Further work is thus warranted to assess their utility as diagnostic/therapeutic targets.

scholarly journals 226.Regulated expression of adhesion and anti-adhesion molecules in mouse endometrium during early pregnancy

2004 ◽  
Vol 16 (9) ◽  
pp. 226 ◽  
Author(s):  
M. J. Jasper ◽  
A. Stocker ◽  
S. A. Robertson
Keyword(s):  
Real Time ◽  
Adhesion Molecules ◽  
Early Pregnancy ◽  
Embryo Implantation ◽  
Early Embryo ◽  
Luminal Epithelium ◽  
Paracrine Factors ◽  
Mean Values ◽  
Actin Mrna ◽  
Further Development

To implant and establish the connections that are vital for further development, the early embryo must attach to and then breech the barrier posed by the epithelium of the maternal tract. Expression of adhesion and anti-adhesion molecules in the luminal epithelium of the endometrium are thought to fluctuate in a temporal pattern to 'frame' the implantation site, with their expression regulated by endocrine and paracrine factors. Anti-adhesion molecules, such as members of the mucin family, provide a barrier to implantation in sites or at times unsuitable for embryo development. Expression of adhesion molecules, or specific integrins, are thought to aid in the adhesion of the embryo, allowing it to induce changes in the underlying tissue promoting embryo invasion and pregnancy. The aim of this study was to quantitate the expression of mRNA encoding the integrins αυ, α4 and β3 and MUC1 and MUC4 from Day 0 (oestrous) to Day 4 of pregnancy (implantation) using quantitative real time RT-PCR. Uterine tissues were collected at oestrous and at Days 1, 2, 3 and 4 of pregnancy (Day 1 corresponding to the presence of a vaginal plug), total RNA was extracted, DNAse treated, reverse transcribed into cDNA, and quantified by real-time PCR using SYBR Green chemistry. All specific primers were designed using GenBank sequences and data were normalised to β-actin mRNA expression. Expression of MUC1 and MUC4 mRNAs was dramatically reduced, with mean values 20-fold and 100-fold less than at oestrous respectively, by Day 4 of pregnancy. In contrast, expression of mRNAs encoding integrins αυ, α4 and β3 was detected throughout early pregnancy. These data demonstrate that adhesion and anti-adhesion molecules are differentially expressed in the murine uterus during early pregnancy and may be key mediators in embryo implantation, promoting attachment of the embryo to the luminal epithelium in an environment conducive to embryo growth and development. Supported by a Clive & Vera Ramaciotti Project Grant to MJ Jasper.

scholarly journals Isolation and Identification of Exosomes from Feline Plasma, Urine and Adipose-Derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Dongsheng Li ◽  
Huina Luo ◽  
Huimin Ruan ◽  
Zhisheng Chen ◽  
Shengfeng Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transmembrane Protein ◽  
Cell Communication ◽  
Phospholipid Bilayer ◽  
Differential Centrifugation ◽  
Isolation And Identification ◽  
Feasible Method ◽  
Transmission Electron ◽  
Mediate Cell

Abstract Background: Exosomes, internal proteins, lipids, and nucleic acids coated by phospholipid bilayer membranes, are one type of small extracellular vesicles, which can mediate cell-cell communication. In recent years, exosomes have gained considerable scientific interest due to their widely applied prospect in the diagnosis and therapeutics of human and animal diseases. In this study, we describe for the first time a feasible method designed to isolate and characterize exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells. Results: Exosomes from feline plasma, urine and adipose-derived mesenchymal stem cells were successfully isolated by differential centrifugation. Quantification and sizing of exosomes were assessed by transmission electron microscopy, flow nano analysis and western blotting. Detected particles showed the normal size (30-100 nm) and morphology described for exosomes, as well as presence of the transmembrane protein (TSG101, CD9, CD63, and CD81) known as exosomal marker.Conclusions: The results suggest that differential centrifugation is a feasible method for isolation of exosomes from different types of feline samples. Moreover, these exosomes can be used to further diagnosis and therapeutics in veterinary pre-clinical and clinical studies.

Advances in microglia cellular models: focus on extracellular vesicle production

2021 ◽  
Author(s):  
Lorenzo Ceccarelli ◽  
Laura Marchetti ◽  
Chiara Giacomelli ◽  
Claudia Martini
Keyword(s):  
Cell Communication ◽  
Extracellular Vesicle ◽  
Cellular Models ◽  
Advantages And Disadvantages ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Harmful Effects ◽  
Brain Homeostasis

Microglia are the major component of the innate immune system in the central nervous system. They promote the maintenance of brain homeostasis as well as support inflammatory processes that are often related to pathological conditions such as neurodegenerative diseases. Depending on the stimulus received, microglia cells dynamically change their phenotype releasing specific soluble factors and largely modify the cargo of their secreted extracellular vesicles (EVs). Despite the mechanisms at the basis of microglia actions have not been completely clarified, the recognized functions exerted by their EVs in patho-physiological conditions represent the proof of the crucial role of these organelles in tuning cell-to-cell communication, promoting either protective or harmful effects. Consistently, in vitro cell models to better elucidate microglia EV production and mechanisms of their release have been increased in the last years. In this review, the main microglial cellular models that have been developed and validated will be described and discussed, with particular focus on those used to produce and derive EVs. The advantages and disadvantages of their use will be evidenced too. Finally, given the wide interest in applying EVs in diagnosis and therapy too, the heterogeneity of available models for producing microglia EVs is here underlined, to prompt a cross-check or comparison among them.

Investigating the growth performance, meat quality, immune function and proteomic profiles of plasmal exosomes in Lactobacillus plantarum-treated immunosuppressive broilers

2021 ◽  
Author(s):  
Huawei Liu ◽  
Fan Zhao ◽  
Kai Zhang ◽  
Jinshan Zhao ◽  
Yang Wang
Keyword(s):  
Immune Function ◽  
Growth Performance ◽  
Lactobacillus Plantarum ◽  
Meat Quality ◽  
Cell Communication ◽  
Mediate Cell

Exosomes are extracellular membranous nanovesicles that carry functional molecules to mediate cell-to-cell communication. Untile now, whether probiotics improve the immune function of broilers by plasmal exosomal cargo is unclear. In...

scholarly journals The Impact of Diet on the Involvement of Non-Coding RNAs, Extracellular Vesicles, and Gut Microbiome-Virome in Colorectal Cancer Initiation and Progression

2020 ◽  
Vol 10 ◽  
Author(s):  
Bene A. Ekine-Afolabi ◽  
Anoka A. Njan ◽  
Solomon O. Rotimi ◽  
Anu R. I. ◽  
Attia M. Elbehi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Dietary Factors ◽  
Tumor Onset ◽  
Non Coding Rnas ◽  
The Impact

Cancer is the major cause of morbidity and mortality in the world today. The third most common cancer and which is most diet related is colorectal cancer (CRC). Although there is complexity and limited understanding in the link between diet and CRC, the advancement in research methods have demonstrated the involvement of non-coding RNAs (ncRNAs) as key regulators of gene expression. MicroRNAs (miRNAs) which are a class of ncRNAs are key players in cancer related pathways in the context of dietary modulation. The involvement of ncRNA in cancer progression has recently been clarified throughout the last decade. ncRNAs are involved in biological processes relating to tumor onset and progression. The advances in research have given insights into cell to cell communication, by highlighting the pivotal involvement of extracellular vesicle (EV) associated-ncRNAs in tumorigenesis. The abundance and stability of EV associated ncRNAs act as a new diagnostic and therapeutic target for cancer. The understanding of the deranging of these molecules in cancer can give access to modulating the expression of the ncRNAs, thereby influencing the cancer phenotype. Food derived exosomes/vesicles (FDE) are gaining interest in the implication of exosomes in cell-cell communication with little or no understanding to date on the role FDE plays. There are resident microbiota in the colon; to which the imbalance in the normal intestinal occurrence leads to chronic inflammation and the production of carcinogenic metabolites that lead to neoplasm. Limited studies have shown the implication of various types of microbiome in CRC incidence, without particular emphasis on fungi and protozoa. This review discusses important dietary factors in relation to the expression of EV-associated ncRNAs in CRC, the impact of diet on the colon ecosystem with particular emphasis on molecular mechanisms of interactions in the ecosystem, the influence of homeostasis regulators such as glutathione, and its conjugating enzyme-glutathione S-transferase (GST) polymorphism on intestinal ecosystem, oxidative stress response, and its relationship to DNA adduct fighting enzyme-0-6-methylguanine-DNA methyltransferase. The understanding of the molecular mechanisms and interaction in the intestinal ecosystem will inform on the diagnostic, preventive and prognosis as well as treatment of CRC.

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