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

• Published in: Biology of reproduction Vol. 106; no. 3; pp. 408 - 424
• Main Authors: Aleksejeva, Elina, Zarovni, Natasa, Dissanayake, Keerthie, Godakumara, Kasun, Vigano, Paola, Fazeli, Alireza, Jaakma, Ülle, Salumets, Andres
• Format: Journal Article
• Language: English
• Published: United States Society for the Study of Reproduction 19-03-2022; Oxford University Press
• Subjects: Animals; assisted reproduction; Cell interactions; embryo; Embryo Implantation; Embryo, Mammalian; Endometrium; exosomes; Extracellular Vesicles; Female; Fertilization; gametes; implantation; Infertility; Mammals; Medical research; Medicin och hälsovetenskap; Membrane vesicles; Menstrual cycle; oviduct; Reproduction; Reproductive system; Reproductive technologies; Reproductive technology; REVIEW; Secretions; Steroid hormones; assisted reproduction; implantation; oviduct; extracellular vesicles; fertilization; exosomes; gametes; embryo
• ISSN: 0006-3363; 1529-7268; 1529-7268
• DOI: 10.1093/biolre/ioab245

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. Summary Sentence Owing to their influences on gamete maturation, embryo–maternal interactions in the oviduct, and during implantation, extracellular vesicles have the potential to be used in assisted reproduction if technological hindrances can be overcome. Graphical Abstract