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Non-human primates as a translational model for the study of male reproductive health

Nature Reviews Urology (2025)Cite this article

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Abstract

Male fertility is complex and influenced by genetic, hormonal, environmental and lifestyle factors. However, limitations to human studies necessitate the use of reliable preclinical models to better understand the underlying mechanisms of male fertility. Rhesus macaques (Macaca mulatta), with their close genetic and physiological similarities to humans, offer an invaluable model for male reproductive health studies. The suitability of rhesus macaques for studying male infertility is based on similarities in spermatogenesis, hormonal cycles and the way in which assisted reproductive technologies can be applied, and key differences and similarities between human and rhesus macaque sperm structure, function and cryopreservation techniques highlight the translational potential of findings derived from macaque models. Furthermore, insights into the epigenetic and proteomic characteristics of sperm in both species improve understanding of how these findings can help to advance clinical diagnostics, male contraception and fertility preservation and illuminate the regulatory omics of normal reproduction. Thus, the rhesus macaque model offers critical insights into male fertility and studies in this species could contribute to advances in therapies for male infertility.

Key points

  • Rhesus macaques share considerable genetic and physiological parallels with humans, including 97% conserved gene-coding regions, making them a robust model for studying male reproductive health.

  • The hypothalamus–pituitary–gonadal axis in rhesus macaques closely resembles that of humans, enabling detailed studies of hormonal regulation of reproduction.

  • The macaque model supports research into assisted reproductive and emerging technologies, helping to refine techniques for human reproductive support.

  • Non-human primates are indispensable models for refining assisted reproductive technologies and developing male contraceptives, offering direct translational value for human health.

  • Non-human primate models present inherent limitations, including species-specific biological divergences, ethical and welfare considerations, and financial and temporal demands.

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Fig. 1: Comparisons in testicular histology between humans and rhesus macaques.
Fig. 2: The hypothalamus–pituitary–testis axis.
Fig. 3: Comparative biology of reproduction.
Fig. 4: Comparative sperm morphology.

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Acknowledgements

J.O.L. is funded by NIH NIDA DP1 DA056793. C.A.E is funded by NIH OD R01OD028223 and previously by NIH NIEHS K22ES025418.

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Author notes

  1. These authors contributed equally: Carol B. Hanna, Jamie O. Lo.

Authors and Affiliations

  1. Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA

    R. Clayton Edenfield, Rahul J. D’Mello, Olivia L. Hagen, Jason A. Graham, Carol B. Hanna & Jamie O. Lo

  2. Department of Urology, Oregon Health & Science University, Portland, OR, USA

    Jasper C. Bash, Jason C. Hedges & Jamie O. Lo

  3. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA

    Lyndsey E. Shorey-Kendrick

  4. Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA

    Rahul J. D’Mello & Jamie O. Lo

  5. Department of Pathology, Oregon Health & Science University, Portland, OR, USA

    Travis L. Rice-Stitt

  6. Department of Obstetrics, Gynecology, and Reproductive Services, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Kyle E. Orwig

  7. Department of Environmental Health Science, University of Georgia College of Public Health, Athens, GA, USA

    Charles A. Easley

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Contributions

R.C.E., J.C.B., C.B.H. and J.O.L. researched data for the article. All authors contributed substantially to discussion of the content. R.C.E., J.C.B., C.B.H. and J.O.L. wrote the article. All authors reviewed and edited the manuscript before submission. R.C.E. and T.L.R.-S. researched data for the article. R.C.E. write the manuscript. All authors contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to R. Clayton Edenfield.

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Edenfield, R.C., Bash, J.C., Shorey-Kendrick, L.E. et al. Non-human primates as a translational model for the study of male reproductive health. Nat Rev Urol (2025). https://doi.org/10.1038/s41585-025-01062-2

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