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A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility

Author

Listed:
  • Daiji Kiyozumi

    (Osaka University, Suita
    PRESTO, Japan Science and Technology Agency, Kawaguchi)

  • Kentaro Shimada

    (Osaka University, Suita
    Osaka University, Suita)

  • Michael Chalick

    (Tel Aviv University)

  • Chihiro Emori

    (Osaka University, Suita)

  • Mayo Kodani

    (Osaka University, Suita
    Osaka University, Suita)

  • Seiya Oura

    (Osaka University, Suita
    Osaka University, Suita)

  • Taichi Noda

    (Osaka University, Suita)

  • Tsutomu Endo

    (Osaka University, Suita)

  • Martin M. Matzuk

    (Baylor College of Medicine)

  • Daniel H. Wreschner

    (Tel Aviv University)

  • Masahito Ikawa

    (Osaka University, Suita
    Osaka University, Suita
    Osaka University, Suita
    The University of Tokyo, Minato-ku)

Abstract

The mammalian spermatozoa produced in the testis require functional maturation in the epididymis for their full competence. Epididymal sperm maturation is regulated by lumicrine signalling pathways in which testis-derived secreted signals relocate to the epididymis lumen and promote functional differentiation. However, the detailed mechanisms of lumicrine regulation are unclear. Herein, we demonstrate that a small secreted protein, NELL2-interacting cofactor for lumicrine signalling (NICOL), plays a crucial role in lumicrine signalling in mice. NICOL is expressed in male reproductive organs, including the testis, and forms a complex with the testis-secreted protein NELL2, which is transported transluminally from the testis to the epididymis. Males lacking Nicol are sterile due to impaired NELL2-mediated lumicrine signalling, leading to defective epididymal differentiation and deficient sperm maturation but can be restored by NICOL expression in testicular germ cells. Our results demonstrate how lumicrine signalling regulates epididymal function for successful sperm maturation and male fertility.

Suggested Citation

  • Daiji Kiyozumi & Kentaro Shimada & Michael Chalick & Chihiro Emori & Mayo Kodani & Seiya Oura & Taichi Noda & Tsutomu Endo & Martin M. Matzuk & Daniel H. Wreschner & Masahito Ikawa, 2023. "A small secreted protein NICOL regulates lumicrine-mediated sperm maturation and male fertility," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37984-x
    DOI: 10.1038/s41467-023-37984-x
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    References listed on IDEAS

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    1. Naokazu Inoue & Masahito Ikawa & Ayako Isotani & Masaru Okabe, 2005. "The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs," Nature, Nature, vol. 434(7030), pages 234-238, March.
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