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  • Review Article
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Human sperm RNA in male infertility

Nature Reviews Urology (2024)Cite this article

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Abstract

The function and value of specific sperm RNAs in apparently idiopathic male infertility are currently poorly understood. Whether differences exist in the sperm RNA profile between patients with infertility and fertile men needs clarification. Similarly, the utility of sperm RNAs in predicting successful sperm retrieval and assisted reproductive technique (ART) outcome is unknown. Patients with infertility and fertile individuals seem to have differences in the expression of non-coding RNAs that regulate genes controlling spermatogenesis. Several RNAs seem to influence embryo quality and development. Also, RNA types seem to predict successful sperm retrieval in patients with azoospermia. These findings suggest that sperm RNAs could influence decision-making during the management of patients with infertility. This evidence might help to identify possible therapeutic approaches aimed at modulating the expression of dysregulated genes in patients with infertility. Performing prospective studies with large sample sizes is necessary to investigate cost-effective panels consisting of proven molecular targets to ensure that this evidence can be translated to clinical practice.

Key points

  • Evidence supports the presence of different seminal and testicular RNA profiles between men with infertility and fertile men.

  • Current study results indicate a role for testicular and seminal RNA profiles in predicting successful sperm retrieval.

  • RNA expression in spermatozoa seems to influence embryo quality and viability and might have an effect on the outcome of assisted reproductive techniques.

  • Quality of evidence is low, targets and tissues used among studies are heterogeneous and the sample sizes are small. Standardization of evidence is important to transfer this knowledge to clinical practice.

  • RNA expression has most often been investigated in seminal plasma and spermatozoa to evaluate its predictive role in sperm recovery and embryo quality, respectively. Their use as RNA sources in future studies will enable the standardization of evidence.

  • Evidence summarized in this Review could be used to enrich and standardize diagnostic platforms able to quantify the expression of RNAs selected in an evidence-based manner, and to test their role in the clinical management of patients and decision-making in well-sized studies.

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Fig. 1: miR-23a/b-5p might regulate spermatogenesis through interaction with PFKFB4, TEX15, HMMR and SPATA6.
Fig. 2: Mechanisms through which mir-375, miR-21, mir-140 and mir-34c might influence embryo development.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

    Rossella Cannarella, Andrea Crafa, Roberto Curto, Laura M. Mongioì, Vincenzo Garofalo, Vittorio Cannarella, Rosita A. Condorelli, Sandro La Vignera & Aldo E. Calogero

  2. Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

    Rossella Cannarella

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  1. Rossella Cannarella
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Contributions

A.C., L.M.M., V.G. and V.C. researched data for the article. R. Cannarella, S.L.V. and A.E.C. contributed substantially to discussion of the content. R. Curto wrote the article. R. Cannarella, R.A.C. and A.E.C. reviewed and/or edited the manuscript before submission.

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Cannarella, R., Crafa, A., Curto, R. et al. Human sperm RNA in male infertility. Nat Rev Urol (2024). https://doi.org/10.1038/s41585-024-00920-9

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