Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Sep 5;3(9):e70007.
doi: 10.1002/jex2.70007. eCollection 2024 Sep.

Exploring the potential of in vitro extracellular vesicle generation in reproductive biology

Roksan Franko  1   2 , Marcia de Almeida Monteiro Melo Ferraz  1   2
Affiliations
Review

Exploring the potential of in vitro extracellular vesicle generation in reproductive biology

Roksan Franko et al. J Extracell Biol. .

Erratum in

Abstract

The interest in the growing field of extracellular vesicle (EV) research highlights their significance in intercellular signalling and the selective transfer of biological information between donor and recipient cells. EV studies have provided valuable insights into intercellular communication mechanisms, signal identification and their involvement in disease states, offering potential avenues for manipulating pathological conditions, detecting biomarkers and developing drug-delivery systems. While our understanding of EV functions in reproductive tissues has significantly progressed, exploring their potential as biomarkers for infertility, therapeutic interventions and enhancements in assisted reproductive technologies remains to be investigated. This knowledge gap stems partly from the difficulties associated with large-scale EV production relevant to clinical applications. Most existing studies on EV production rely on conventional 2D cell culture systems, characterized by suboptimal EV yields and a failure to replicate in vivo conditions. This results in the generation of EVs that differ from their in vivo counterparts. Hence, this review firstly delves into the importance of EVs in reproduction to then expand on current techniques for in vitro EV production, specifically examining diverse methods of culture and the potential of bioengineering technologies to establish innovative systems for enhanced EV production.

Keywords: bioengineering; improved EV yield; in vitro EV production.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

FIGURE 1
FIGURE 1
Roles of EVs in different female reproductive tissues. EVs differ in their molecular content and role in biological processes based on cell of origin and its environment. Hence, EVs produced in different reproductive tissues also have different roles influencing important reproductive events. In the ovary (a), follicular EVs are involved in supporting the progression of folliculogenesis, oocyte maturation and in several signalling pathways that reinforces oocyte competence. In the oviduct (b), EVs from oviductal cells, oocytes, sperm and embryos are present, driving key reproductive events such as oocyte maturation, sperm capacitation and early embryo development. Endometrial Evs (c) and their interaction with embryonic EVs are crucial for endometrial receptivity, trophoblast adhesion and angiogenesis. Figure was made using Biorender, adapted from Kurian and Modi (2019) and Qamar et al. (2020).
FIGURE 2
FIGURE 2
Bioengineering platforms for improved EV production. The figure illustrates diverse bioengineering approaches employed in the in vitro production of extracellular vesicles (EVs), showcasing the continuum between throughput and physiological relevance. Each technology is strategically positioned on this spectrum to highlight its characteristics in terms of scalability and mimicry of natural physiological conditions. Figure was made using Biorender.
See this image and copyright information in PMC

References

    1. Abu‐Halima, M. , Häusler, S. , Backes, C. , Fehlmann, T. , Staib, C. , Nestel, S. , Nazarenko, I. , Meese, E. , & Keller, A. (2017). Micro‐ribonucleic acids and extracellular vesicles repertoire in the spent culture media is altered in women undergoing In Vitro Fertilization. Scientific Reports, 7(1), 13525. 10.1038/s41598-017-13683-8 - DOI - PMC - PubMed
    1. Adam, S. , Elfeky, O. , Kinhal, V. , Dutta, S. , Lai, A. , Jayabalan, N. , Nuzhat, Z. , Palma, C. , Rice, G. E. , & Salomon, C. (2017). Review: Fetal‐maternal communication via extracellular vesicles—Implications for complications of pregnancies. Placenta, 54, 83–88. 10.1016/j.placenta.2016.12.001 - DOI - PubMed
    1. Aguilera, C. , Velásquez, A. E. , Gutierrez‐Reinoso, M. A. , Wong, Y. S. , Melo‐Baez, B. , Cabezas, J. , Caamaño, D. , Navarrete, F. , Rojas, D. , Riadi, G. , Castro, F. O. , & Rodriguez‐Alvarez, L. (2023). Extracellular vesicles secreted by pre‐hatching bovine embryos produced in vitro and in vivo alter the expression of IFNtau‐stimulated genes in bovine endometrial cells. International Journal of Molecular Sciences, 24(8), 7438. 10.3390/ijms24087438 - DOI - PMC - PubMed
    1. Ahmed, E. M. (2015). Hydrogel: Preparation, characterization, and applications: A review. Journal of Advanced Research, 6(2), 105–121. 10.1016/j.jare.2013.07.006 - DOI - PMC - PubMed
    1. Ahn, J. , Yoon, M. J. , Hong, S. H. , Cha, H. , Lee, D. , Koo, H. S. , Ko, J. E. , Lee, J. , Oh, S. , Jeon, N. L. , & Kang, Y. J. (2021). Three‐dimensional microengineered vascularised endometrium‐on‐a‐chip. Human Reproduction, 36(10), 2720–2731. 10.1093/humrep/deab186 - DOI - PMC - PubMed

LinkOut - more resources