A1 Refereed original research article in a scientific journal

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




AuthorsZhang 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

PublisherNATURE PUBLISHING GROUP

Publication year2019

JournalNature Communications

Journal name in sourceNATURE COMMUNICATIONS

Journal acronymNAT COMMUN

Article numberARTN 777

Volume10

Number of pages12

ISSN2041-1723

eISSN2041-1723

DOIhttps://doi.org/10.1038/s41467-019-08730-z

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/39671209


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 (ArKl) in which the conserved SUMO acceptor lysines of AR are permanently abolished (Ar-K381R, (K500R)) ArKl males develop normally, without apparent defects in their systemic androgen action in reproductive tissues. However, the ArKl 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.

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