A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction
Tekijät: 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
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2019
Journal: Nature Communications
Tietokannassa oleva lehden nimi: NATURE COMMUNICATIONS
Lehden akronyymi: NAT COMMUN
Artikkelin numero: ARTN 777
Vuosikerta: 10
Sivujen määrä: 12
ISSN: 2041-1723
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-019-08730-z
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/39671209
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
