• PMID: 30770815
• Gene Name: AR
• Condition: Post testicular sperm maturation, Male infertility, epididymal dysfunction
• Association: Associated
• Mutation: K381R, K500R
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Post testicular sperm maturation, Male infertility, epididymal dysfunction

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

Zhang FP, Malinen M, Mehmood A, Lehtiniemi T, Jääskeläinen T, Niskanen EA, Korhonen H, Laiho A, Elo LL, Ohlsson C, Kotaja N, Poutanen M, Sipilä P, Palvimo JJ.

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 (Ar(K381R, 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. FAU - Zhang, Fu-Ping AU - Zhang FP AD - Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520, Turku, Finland. AD - Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, FI-20520, Turku, Finland. FAU - Malinen, Marjo AU - Malinen M AD - Department of Environmental and Biological Sciences, University of Eastern Finland, FI-80101, Joensuu, Finland. FAU - Mehmood, Arfa AU - Mehmood A AD - Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20014, Turku, Finland. FAU - Lehtiniemi, Tiina AU - Lehtiniemi T AD - Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520, Turku, Finland. FAU - Jääskeläinen, Tiina AU - Jääskeläinen T AD - Institute of Biomedicine, University of Eastern Finland, FI-70211, Kuopio, Finland. FAU - Niskanen, Einari A AU - Niskanen EA AD - Institute of Biomedicine, University of Eastern Finland, FI-70211, Kuopio, Finland. FAU - Korhonen, Hanna AU - Korhonen H AD - Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520, Turku, Finland. FAU - Laiho, Asta AU - Laiho A AD - Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20014, Turku, Finland. FAU - Elo, Laura L AU - Elo LL AD - Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20014, Turku, Finland. FAU - Ohlsson, Claes AU - Ohlsson C AD - Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, 41345, Gothenburg, Sweden. FAU - Kotaja, Noora AU - Kotaja N AD - Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520, Turku, Finland. FAU - Poutanen, Matti AU - Poutanen M AD - Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520, Turku, Finland. AD - Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, FI-20520, Turku, Finland. AD - Institute of Medicine, The Sahlgrenska Academy, Gothenburg University, 41345, Gothenburg, Sweden. FAU - Sipilä, Petra AU - Sipilä P AD - Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520, Turku, Finland. AD - Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, FI-20520, Turku, Finland.