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Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction
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Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction
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Journal Article
Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction
2019
Overview
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
K381R
,
K500R
). 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.
SUMOylation is known to regulate androgen receptor (AR) activity in cultured cells. Here, using SUMOylation-deficient AR knock-in mice, the authors demonstrate that SUMOylation is required for AR-related gene expression specifically in the epididymal tissues, but not the testis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/88
/ 49/15
/ 49/91
/ 631/337
/ 631/443
/ 64/110
/ Animals
/ Epididymis - physiopathology
/ family
/ gene
/ health
/ Humanities and Social Sciences
/ Humans
/ Infertility, Male - metabolism
/ Infertility, Male - pathology
/ Infertility, Male - physiopathology
/ Male
/ Males
/ Medical Genetics and Genomics
/ Medicinsk genetik och genomik
/ Mice
/ pathway
/ Receptors, Androgen - genetics
/ Receptors, Androgen - metabolism
/ Science
/ Science & Technology - Other Topics
/ Sperm
/ Spermatogenesis - physiology
/ sumo
