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Microfluidics facilitating the use of small extracellular vesicles in innovative approaches to male infertility

Nature Reviews Urology volume 20, pages 66–95 (2023)Cite this article

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Abstract

Sperm are transcriptionally and translationally quiescent and, therefore, rely on the seminal plasma microenvironment for function, survival and fertilization of the oocyte in the oviduct. The male reproductive system influences sperm function via the binding and fusion of secreted epididymal (epididymosomes) and prostatic (prostasomes) small extracellular vesicles (S-EVs) that facilitate the transfer of proteins, lipids and nucleic acids to sperm. Seminal plasma S-EVs have important roles in sperm maturation, immune and oxidative stress protection, capacitation, fertilization and endometrial implantation and receptivity. Supplementing asthenozoospermic samples with normospermic-derived S-EVs can improve sperm motility and S-EV microRNAs can be used to predict non-obstructive azoospermia. Thus, S-EV influence on sperm physiology might have both therapeutic and diagnostic potential; however, the isolation of pure populations of S-EVs from bodily fluids with current conventional methods presents a substantial hurdle. Many conventional techniques lack accuracy, effectiveness, and practicality; yet microfluidic technology has the potential to simplify and improve S-EV isolation and detection.

Key points

  • Epididymosomes and prostasomes, the two distinct populations of seminal plasma small extracellular vesicles (S-EVs), have substantial roles in sperm function, survival and fertilization of the oocyte.

  • Male reproductive S-EV protein and microRNA cargo might serve as biomarkers for infertility and reproductive dysfunction.

  • Conventional methods of S-EV isolation require often laborious or costly workflows with suboptimal results but have received substantial interest in cancer therapeutics and diagnostics.

  • Microfluidic technology has the potential for miniaturization and simplification of S-EV isolation and analysis for use in point-of-need diagnostics in male infertility.

  • Infertility treatment can use technology developed for cancer diagnostics and therapeutics to approach idiopathic infertility.

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Fig. 1: Biogenesis and release of EVs.
Fig. 2: Male reproductive S-EVs from the epididymis and prostate and their roles in sperm maturation, protection and interaction with the oocyte.
Fig. 3: Potential seminal plasma small extracellular vesicle protein biomarkers and their involvement in key events during sperm development and function.
Fig. 4: Conventional methods of isolating S-EVs and EVs from biofluids.
Fig. 5: Examples of microfluidic-based methods of S-EV isolation and detection.
Fig. 6: Idealized seminal plasma diagnostic systems.

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Authors and Affiliations

  1. School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, Australia

    Dale M. Goss, Steven A. Vasilescu & Majid E. Warkiani

  2. IVF Australia, Sydney, NSW, Australia

    Dale M. Goss & Gavin Sacks

  3. NeoGenix Biosciences pty ltd, Sydney, NSW, Australia

    Steven A. Vasilescu

  4. University of New South Wales, Sydney, NSW, Australia

    Gavin Sacks

  5. Melbourne IVF, East Melbourne, VIC, Australia

    David K. Gardner

  6. School of BioSciences, University of Melbourne, Melbourne, VIC, Australia

    David K. Gardner

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D.M.G. researched data for the article. All authors contributed substantially to discussion of the content. D.M.G. wrote the article. D.M.G., S.A.V., D.K.G. and M.E.W. reviewed and/or edited the manuscript before submission.

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Goss, D.M., Vasilescu, S.A., Sacks, G. et al. Microfluidics facilitating the use of small extracellular vesicles in innovative approaches to male infertility. Nat Rev Urol 20, 66–95 (2023). https://doi.org/10.1038/s41585-022-00660-8

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