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Extracellular Vesicles in Reproduction 2.0
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Extracellular Vesicles in Reproduction 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (28 December 2022) | Viewed by 27862

Special Issue Editors

Prof. Dr. Heriberto Rodriguez-Martinez

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, SE-58185 Linköping, Sweden
Interests: andrology; reproductive biotechnologies; gamete interactions
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jordi Roca

E-Mail Website
Guest Editor
Department of Medicine and Animal Surgery, Faculty of Veterinary Science, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain
Interests: spermatozoa; seminal plasma; extracellular vesicles; proteomics; cytokines
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Emilio A. Martinez

E-Mail Website
Guest Editor
Department of Animal Medicine and Surgery, Faculty of Veterinary, University of Murcia, 30100 Murcia, Spain
Interests: animal reproduction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The homeostasis of an individual depends basically on the ability of the differences cells, systems, and body compartments to interact via complex processes of communication. Among these, we know of humoral, hormonal, and nervous processes, and from the initial findings from the 1960s to today we include the role of cell-derived vesicles that communicate cell-to-cell beyond intercellular organized contacts, and vesicles that circulate in intercellular matrixes and secretions, lymph fluid, or blood to gain contact and mediate stimulus and responses at long distances from the originating cell. These extracellular vesicles (EVs) are further distinguished as exosomes, microvesicles, or apoptotic bodies, the latter being mostly related to cell death and nearby, local contacts, while the first names are related to systemic cell communication. All EVs have in common that they carry loads of molecules (proteins, peptides, lipids, carbohydrates, and nucleic acids) or even organelles (apoptotic bodies) with the capacity of respond to stimuli, intervene in metabolic pathways, or influence gene expression. Often having the characteristics of the originating cell, they serve as biomarkers of origin and of function beyond a specific target. The reproductive system is able to communicate via EVs, with some EVs playing important roles in spermatogenesis, sperm maturation, oogenesis, and embryogenesis, as well as influencing other systems, including the immune system to modulate immune responses, during the development and function of hemi-allogeneic organs as the placenta or the survival of the foetus throughout pregnancy.

This Issue of IJMS is focused on "Extracellular Vesicles in Reproduction”. The Issue welcomes papers covering EVs characterization, quantification, disclosure of their load, and elucidation of their biogenesis and roles when modulating reproductive events. The Issue welcomes novel research, certainly of comparative aspects but also of methodological papers, as well as insightful, critical reviews in these areas.

Prof. Dr. Heriberto Rodriguez-Martinez
Prof. Dr. Jordi Roca
Prof. Dr. Emilio A. Martinez
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • extracellular vesicles
  • exosomes
  • microvesicles
  • apoptotic bodies
  • reproductive processes
  • spermatogenesis
  • sperm maturation
  • seminal plasma
  • spermatozoa
  • sperm capacitation
  • fertility
  • pregnancy
  • immune modulation
  • immune tolerance
  • proteomics
  • transcriptomics
  • epigenomics
  • metabolomics

Related Special Issues

Published Papers (6 papers)

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Research

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13 pages, 5087 KiB  
Article
Diversity of Extracellular Vesicles in Human Follicular Fluid: Morphological Analysis and Quantification
by Anne-Sophie Neyroud, Regina Maria Chiechio, Gregory Moulin, Solène Ducarre, Claire Heichette, Aurélien Dupont, Mathieu Budzynski, Pascale Even-Hernandez, Maria Jose Lo Faro, Marina Yefimova, Valérie Marchi and Célia Ravel
Int. J. Mol. Sci. 2022, 23(19), 11676; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911676 - 02 Oct 2022
Cited by 8 | Viewed by 1769
Abstract
The oocyte microenvironment constituted by the follicular fluid (FF) is a key for the optimal development of female gametes. Its composition reflects the physiological state of the ovarian follicle. The particularity of FF is to contain a huge diversity of extracellular vesicles specific [...] Read more.
The oocyte microenvironment constituted by the follicular fluid (FF) is a key for the optimal development of female gametes. Its composition reflects the physiological state of the ovarian follicle. The particularity of FF is to contain a huge diversity of extracellular vesicles specific to women, in the same way as seminal plasma in men. Here, we described and compared morphological aspects of broad subcategories of human FF-related Extracellular Vesicles (EVs). EVs participate in physiological and pathological processes and have potential applications in diagnostics or therapeutics. EVs isolated from FF are involved in different biological functions related to follicular growth, oocyte maturation, and embryo development. However, knowledge on the morphology of FF-derived EVs is limited, mainly due to their sub-micrometer size and to intrinsic limitations in methods applied for their characterization. The aim of this study was to provide a comprehensive morphological description of EVs from FF of healthy subjects and quantification. EVs separation was realized by centrifugation, with comparison of the EV yield obtained from differential centrifugation and one-step ultracentrifugation. Cryo-Transmission Electron Microscopy was used to reveal the morphology, size, and phenotype of EVs. Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) were used to quantify and analyze the size distribution for each centrifugation step. We performed a comprehensive inventory of human follicular fluid EVs. We show that human FF contains a huge diversity of EVs. This study brings novel insights on EVs from normal FF and provides a reference for further studies of EVs in ovarian diseases. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Reproduction 2.0)
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19 pages, 3085 KiB  
Article
Embryonic Trophectoderm Secretomics Reveals Chemotactic Migration and Intercellular Communication of Endometrial and Circulating MSCs in Embryonic Implantation
by Alexandra Calle, Víctor Toribio, María Yáñez-Mó and Miguel Ángel Ramírez
Int. J. Mol. Sci. 2021, 22(11), 5638; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115638 - 26 May 2021
Cited by 12 | Viewed by 2772
Abstract
Embryonic implantation is a key step in the establishment of pregnancy. In the present work, we have carried out an in-depth proteomic analysis of the secretome (extracellular vesicles and soluble proteins) of two bovine blastocysts embryonic trophectoderm primary cultures (BBT), confirming different epithelial–mesenchymal [...] Read more.
Embryonic implantation is a key step in the establishment of pregnancy. In the present work, we have carried out an in-depth proteomic analysis of the secretome (extracellular vesicles and soluble proteins) of two bovine blastocysts embryonic trophectoderm primary cultures (BBT), confirming different epithelial–mesenchymal transition stages in these cells. BBT-secretomes contain early pregnancy-related proteins and angiogenic proteins both as cargo in EVs and the soluble fraction. We have demonstrated the functional transfer of protein-containing secretome between embryonic trophectoderm and maternal MSC in vitro using two BBT primary cultures eight endometrial MSC (eMSC) and five peripheral blood MSC (pbMSC) lines. We observed that eMSC and pbMSC chemotax to both the soluble fraction and EVs of the BBT secretome. In addition, in a complementary direction, we found that the pattern of expression of implantation proteins in BBT-EVs changes depending on: (i) their epithelial–mesenchymal phenotype; (ii) as a result of the uptake of eMSC- or pbMSC-EV previously stimulated or not with embryonic signals (IFN-); (iii) because of the stimulation with the endometrial cytokines present in the uterine fluid in the peri-implantation period. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Reproduction 2.0)
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Review

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19 pages, 1003 KiB  
Review
The Roles of Extracellular Vesicles and Organoid Models in Female Reproductive Physiology
by Riley E. Thompson, Gerrit J. Bouma and Fiona K. Hollinshead
Int. J. Mol. Sci. 2022, 23(6), 3186; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063186 - 16 Mar 2022
Cited by 8 | Viewed by 3296
Abstract
Culture model systems that can recapitulate the anatomy and physiology of reproductive organs, such as three-dimensional (3D) organoid culture systems, limit the cost and welfare concerns associated with a research animal colony and provide alternative approaches to study specific processes in humans and [...] Read more.
Culture model systems that can recapitulate the anatomy and physiology of reproductive organs, such as three-dimensional (3D) organoid culture systems, limit the cost and welfare concerns associated with a research animal colony and provide alternative approaches to study specific processes in humans and animals. These 3D models facilitate a greater understanding of the physiological role of individual cell types and their interactions than can be accomplished with traditional monolayer culture systems. Furthermore, 3D culture systems allow for the examination of specific cellular, molecular, or hormonal interactions, without confounding factors that occur with in vivo models, and provide a powerful approach to study physiological and pathological reproductive conditions. The goal of this paper is to review and compare organoid culture systems to other in vitro cell culture models, currently used to study female reproductive physiology, with an emphasis on the role of extracellular vesicle interactions. The critical role of extracellular vesicles for intercellular communication in physiological processes, including reproduction, has been well documented, and an overview of the roles of extracellular vesicles in organoid systems will be provided. Finally, we will propose future directions for understanding the role of extracellular vesicles in normal and pathological conditions of reproductive organs, utilizing 3D organoid culture systems. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Reproduction 2.0)
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13 pages, 654 KiB  
Review
Angiogenic Properties of Placenta-Derived Extracellular Vesicles in Normal Pregnancy and in Preeclampsia
by Natalia Gebara, Yolanda Correia, Keqing Wang and Benedetta Bussolati
Int. J. Mol. Sci. 2021, 22(10), 5402; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105402 - 20 May 2021
Cited by 19 | Viewed by 5756
Abstract
Angiogenesis is one of the main processes that coordinate the biological events leading to a successful pregnancy, and its imbalance characterizes several pregnancy-related diseases, including preeclampsia. Intracellular interactions via extracellular vesicles (EVs) contribute to pregnancy’s physiology and pathophysiology, and to the fetal–maternal interaction. [...] Read more.
Angiogenesis is one of the main processes that coordinate the biological events leading to a successful pregnancy, and its imbalance characterizes several pregnancy-related diseases, including preeclampsia. Intracellular interactions via extracellular vesicles (EVs) contribute to pregnancy’s physiology and pathophysiology, and to the fetal–maternal interaction. The present review outlines the implications of EV-mediated crosstalk in the angiogenic process in healthy pregnancy and its dysregulation in preeclampsia. In particular, the effect of EVs derived from gestational tissues in pro and anti-angiogenic processes in the physiological and pathological setting is described. Moreover, the application of EVs from placental stem cells in the clinical setting is reported. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Reproduction 2.0)
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28 pages, 5812 KiB  
Review
Seminal Plasma: Relevant for Fertility?
by Heriberto Rodriguez-Martinez, Emilio A. Martinez, Juan J. Calvete, Fernando J. Peña Vega and Jordi Roca
Int. J. Mol. Sci. 2021, 22(9), 4368; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094368 - 22 Apr 2021
Cited by 61 | Viewed by 6506
Abstract
Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines [...] Read more.
Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines and enzymes, cholesterol, DNA and RNA—the latter often protected within epididymis- or prostate-derived extracellular vesicles. It is beyond question that the SP participates in diverse aspects of sperm function pre-fertilization events. The SP also interacts with the various compartments of the tubular genital tract, triggering changes in gene function that prepares for an eventual successful pregnancy; thus, it ultimately modulates fertility. Despite these concepts, it is imperative to remember that SP-free spermatozoa (epididymal or washed ejaculated) are still fertile, so this review shall focus on the differences between the in vivo roles of the SP following semen deposition in the female and those regarding additions of SP on spermatozoa handled for artificial reproduction, including cryopreservation, from artificial insemination to in vitro fertilization. This review attempts, including our own results on model animal species, to critically summarize the current knowledge of the reproductive roles played by SP components, particularly in our own species, which is increasingly affected by infertility. The ultimate goal is to reconcile the delicate balance between the SP molecular concentration and their concerted effects after temporal exposure in vivo. We aim to appraise the functions of the SP components, their relevance as diagnostic biomarkers and their value as eventual additives to refine reproductive strategies, including biotechnologies, in livestock models and humans. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Reproduction 2.0)
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20 pages, 5847 KiB  
Review
Human Placenta Exosomes: Biogenesis, Isolation, Composition, and Prospects for Use in Diagnostics
by Evgeniya E. Burkova, Sergey E. Sedykh and Georgy A. Nevinsky
Int. J. Mol. Sci. 2021, 22(4), 2158; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042158 - 22 Feb 2021
Cited by 37 | Viewed by 6522
Abstract
Exosomes are 40–100 nm nanovesicles participating in intercellular communication and transferring various bioactive proteins, mRNAs, miRNAs, and lipids. During pregnancy, the placenta releases exosomes into the maternal circulation. Placental exosomes are detected in the maternal blood even in the first trimester of pregnancy [...] Read more.
Exosomes are 40–100 nm nanovesicles participating in intercellular communication and transferring various bioactive proteins, mRNAs, miRNAs, and lipids. During pregnancy, the placenta releases exosomes into the maternal circulation. Placental exosomes are detected in the maternal blood even in the first trimester of pregnancy and their numbers increase significantly by the end of pregnancy. Exosomes are necessary for the normal functioning of the placenta and fetal development. Effects of exosomes on target cells depend not only on their concentration but also on their intrinsic components. The biochemical composition of the placental exosomes may cause various complications of pregnancy. Some studies relate the changes in the composition of nanovesicles to placental dysfunction. Isolation of placental exosomes from the blood of pregnant women and the study of protein, lipid, and nucleic composition can lead to the development of methods for early diagnosis of pregnancy pathologies. This review describes the biogenesis of exosomes, methods of their isolation, analyzes their biochemical composition, and considers the prospects for using exosomes to diagnose pregnancy pathologies. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Reproduction 2.0)
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