WFRF:(Laiho P.)
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Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction
- Zhang, F. P. (author)
- Malinen, M. (author)
- Mehmood, A. (author)
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- Lehtiniemi, T. (author)
- Jaaskelainen, T. (author)
- Niskanen, E. A. (author)
- Korhonen, H. (author)
- Laiho, A. (author)
- Elo, L. L. (author)
- Kotaja, N. (author)
- Sipila, P. (author)
- Palvimo, J. J. (author)
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- (creator_code:org_t)
- 2019-02-15
- 2019
- English.
- In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- mouse epididymis
- response element
- gene
- sumo
- ubiquitin
- bioconductor
- integrity
- pathway
- health
- family
- Science & Technology - Other Topics
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Zhang, F. P.
- Malinen, M.
- Mehmood, A.
- Lehtiniemi, T.
- Jaaskelainen, T.
- Niskanen, E. A.
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- Korhonen, H.
- Laiho, A.
- Elo, L. L.
- Ohlsson, Claes, ...
- Kotaja, N.
- Poutanen, Matti
- Sipila, P.
- Palvimo, J. J.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Medical Genetics
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- University of Gothenburg
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