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

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.

Nature communications. 2019 Feb 15*** epublish ***

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, Petra Sipilä, Jorma J Palvimo

Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520, Turku, Finland., Department of Environmental and Biological Sciences, University of Eastern Finland, FI-80101, Joensuu, Finland., Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20014, Turku, Finland., Institute of Biomedicine, University of Eastern Finland, FI-70211, Kuopio, Finland., Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, 41345, Gothenburg, Sweden., Institute of Biomedicine, University of Eastern Finland, FI-70211, Kuopio, Finland. .