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

Nature communications, 2019-02, Vol.10 (1), p.777-777, Article 777 [Peer Reviewed Journal]

This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2019 ;ISSN: 2041-1723 ;EISSN: 2041-1723 ;DOI: 10.1038/s41467-019-08730-z ;PMID: 30770815

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Title:
Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction
Author: Zhang, Fu-Ping ; Malinen, Marjo ; Mehmood, Arfa ; Lehtiniemi, Tiina ; Jääskeläinen, Tiina ; Niskanen, Einari A ; Korhonen, Hanna ; Laiho, Asta ; Elo, Laura L ; Ohlsson, Claes ; Kotaja, Noora ; Poutanen, Matti ; Sipilä, Petra ; Palvimo, Jorma J
Subjects: Androgen receptors ; Androgens ; Animals ; bioconductor ; Chromatin ; Epididymis ; Epididymis - metabolism ; Epididymis - pathology ; Epididymis - physiopathology ; family ; Fertilization ; gene ; Gene expression ; Gene silencing ; health ; Humans ; Infertility ; Infertility, Male - metabolism ; Infertility, Male - pathology ; Infertility, Male - physiopathology ; integrity ; Male ; Males ; Maturation ; Medical Genetics ; Medicinsk genetik ; Mice ; mouse epididymis ; pathway ; Receptors, Androgen - genetics ; Receptors, Androgen - metabolism ; response element ; Science & Technology - Other Topics ; Sperm ; Spermatogenesis ; Spermatogenesis - genetics ; Spermatogenesis - physiology ; sumo ; SUMO protein ; Sumoylation - genetics ; Sumoylation - physiology ; Tissues ; ubiquitin
Is Part Of: Nature communications, 2019-02, Vol.10 (1), p.777-777, Article 777
Description: 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.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 2041-1723
EISSN: 2041-1723
DOI: 10.1038/s41467-019-08730-z
PMID: 30770815
Source: Open Access: DOAJ Directory of Open Access Journals
Open Access: PubMed Central
AUTh Library subscriptions: ProQuest Central
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Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction

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