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Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction

Author

Listed:
  • Fu-Ping Zhang

    (University of Turku
    University of Turku)

  • Marjo Malinen

    (University of Eastern Finland)

  • Arfa Mehmood

    (University of Turku and Åbo Akademi University)

  • Tiina Lehtiniemi

    (University of Turku)

  • Tiina Jääskeläinen

    (University of Eastern Finland)

  • Einari A. Niskanen

    (University of Eastern Finland)

  • Hanna Korhonen

    (University of Turku)

  • Asta Laiho

    (University of Turku and Åbo Akademi University)

  • Laura L. Elo

    (University of Turku and Åbo Akademi University)

  • Claes Ohlsson

    (Gothenburg University)

  • Noora Kotaja

    (University of Turku)

  • Matti Poutanen

    (University of Turku
    University of Turku
    Gothenburg University)

  • Petra Sipilä

    (University of Turku
    University of Turku)

  • Jorma J. Palvimo

    (University of Eastern Finland)

Abstract

Androgen receptor (AR) is regulated by SUMOylation at its transactivation domain. In vitro, the SUMOylation is linked to transcriptional repression and/or target gene-selective regulation. Here, we generated a mouse model (ArKI) in which the conserved SUMO acceptor lysines of AR are permanently abolished (ArK381R, K500R). ArKI males develop normally, without apparent defects in their systemic androgen action in reproductive tissues. However, the ArKI males are infertile. Their spermatogenesis appears unaffected, but their epididymal sperm maturation is defective, shown by severely compromised motility and fertilization capacity of the sperm. Fittingly, their epididymal AR chromatin-binding and gene expression associated with sperm maturation and function are misregulated. AR is SUMOylated in the wild-type epididymis but not in the testis, which could explain the tissue-specific response to the lack of AR SUMOylation. Our studies thus indicate that epididymal AR SUMOylation is essential for the post-testicular sperm maturation and normal reproductive capability of male mice.

Suggested Citation

  • Fu-Ping Zhang & Marjo Malinen & Arfa Mehmood & Tiina Lehtiniemi & Tiina Jääskeläinen & Einari A. Niskanen & Hanna Korhonen & Asta Laiho & Laura L. Elo & Claes Ohlsson & Noora Kotaja & Matti Poutanen &, 2019. "Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08730-z
    DOI: 10.1038/s41467-019-08730-z
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    Cited by:

    1. Moïra Rossitto & Stephanie Déjardin & Chris M. Rands & Stephanie Gras & Roberta Migale & Mahmoud-Reza Rafiee & Yasmine Neirijnck & Alain Pruvost & Anvi Laetitia Nguyen & Guillaume Bossis & Florence Ca, 2022. "TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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