Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520, Turku, Finland.
Turku Center for Disease Modeling (TCDM), Institute of Biomedicine, University of Turku, FI-20520, Turku, Finland.
Nat Commun. 2019 Feb 15;10(1):777. doi: 10.1038/s41467-019-08730-z.
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). 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.
雄激素受体 (AR) 的转录激活结构域的 SUMO 化受到调控。在体外，SUMO 化与转录抑制和/或靶基因选择性调节有关。在这里，我们构建了一个 AR 的保守 SUMO 接受赖氨酸被永久缺失的小鼠模型（ArKI）。ArKI 雄性个体正常发育，其生殖组织中系统性雄激素作用没有明显缺陷。然而，ArKI 雄性个体不育。他们的精子发生似乎没有受到影响，但他们的附睾精子成熟存在缺陷，表现为严重的运动能力受损和受精能力下降。合适的是，他们附睾中的 AR 染色质结合和与精子成熟和功能相关的基因表达受到错误调控。野生型附睾中的 AR 发生 SUMO 化，但睾丸中没有，这可以解释组织对 AR SUMO 化缺失的特异性反应。我们的研究表明，附睾中的 AR SUMO 化对于雄性小鼠的精子后成熟和正常生殖能力至关重要。
