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Male factor infertility

Understanding the roles of the WFDC cluster in sperm development and function

Nature Reviews Urology volume 22, page 69 (2025)Cite this article

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A study in Proceedings of the National Academy of Sciences has elucidated the roles of the whey acidic protein four-disulfide core (WFDC) gene cluster in spermatogenesis and sperm function.

The fact that this reproductive-tract-specific cluster — comprising 11 genes in humans (SPINT3, WFDC6, EPPIN, WFDC8, WFDC9, WFDC10A, WFDC11, WFDC10B, WFDC13, SPINT4 and WFDC3) and 13 in rodents — is so well conserved across species suggests combined critical functions of the cluster.

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References

Original article

  • Kent, K. et al. Large-scale CRISPR/Cas9 deletions within the WFDC gene cluster uncover gene functionality and critical roles in mammalian reproduction. Proc. Natl Acad. Sci. USA 121, e2413195121 (2024)

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Related article

  • Wyrwoll, M. J. et al. Improved phenotypic classification of male infertility to promote discovery of genetic causes. Nat. Rev. Urol. 21, 91–101 (2024)

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  1. Nature Reviews Urology http://www.nature.com/nrurol/

    Annette Fenner

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  1. Annette Fenner
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Correspondence to Annette Fenner.

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Fenner, A. Understanding the roles of the WFDC cluster in sperm development and function. Nat Rev Urol 22, 69 (2025). https://doi.org/10.1038/s41585-025-00999-8

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  • DOI: https://doi.org/10.1038/s41585-025-00999-8

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