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

Publisher: NATURE PUBLISHING GROUP

: 2019

: Nature Communications

: NATURE COMMUNICATIONS

: NAT COMMUN

: ARTN 777

: 10

: 12

: 2041-1723

DOI: https://doi.org/10.1038/s41467-019-08730-z(external)

: https://research.utu.fi/converis/portal/detail/Publication/39671209(external)

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.

s41467-019-08730-z.pdf