Zebrafish androgen receptor is required for spermatogenesis and maintenance of ovarian function.
Zebrafish androgen receptor is required for spermatogenesis and maintenance of ovarian function.
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DOI：
10.18632/oncotarget.24407
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发表时间：
2018-05-11
期刊：
影响因子：
--
通讯作者：
Xiao W
中科院分区：
文献类型：
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作者：
Yu G;Zhang D;Liu W;Wang J;Liu X;Zhou C;Gui J;Xiao W
雄激素受体（AR）是一种核受体蛋白家族成员，是调节雄激素靶基因表达的诱导型转录因子。使用小鼠模型的研究证实了ar在生殖发育中的需要，特别是精子发生。在这里，我们使用CRISPR/Cas9基因打靶技术研究了ar在斑马鱼中的作用。有针对性地破坏斑马鱼的ar增加雌性后代的数量并增加后代的体重。此外，ar-null雄性斑马鱼具有雌性第二性征。更重要的是，在斑马鱼中，有针对性地破坏ar会通过精子发生缺陷和雌性生长期间卵巢早衰导致雄性不育。机制分析表明，这些影响是由更少的增殖细胞和更多的凋亡细胞在ar-空睾丸。此外，生殖发育、雌二醇诱导和激素合成相关基因在睾丸和卵巢中表达失调，生殖内分泌轴紊乱。因此，我们的数据表明，斑马鱼ar是精子发生和卵巢功能维持所需的，这证实了脊椎动物中ar的进化保守功能，并表明ar缺失的斑马鱼是研究与雄激素障碍相关的病理机制的合适模型。
The androgen receptor (AR) is a nuclear receptor protein family member and inducible transcription factor that modulates androgen target gene expression. Studies using a mouse model confirmed the need for ar in reproductive development, particularly spermatogenesis. Here, we investigated the role of ar in zebrafish using CRISPR/Cas9 gene targeting technology. Targeted disruption of ar in zebrafish increases the number of female offspring and increases offspring weight. In addition, ar-null male zebrafish have female secondary sex characteristics. More importantly, targeted disruption of ar in zebrafish causes male infertility via defective spermatogenesis and female premature ovarian failure during growth. Mechanistic assays suggest that these effects are caused by fewer proliferated cells and more apoptotic cells in ar-null testes. Moreover, genes involved in reproductive development, estradiol induction and hormone synthesis were dys-regulated in testes and ovaries and the reproductive-endocrine axis was disordered. Our data thus suggest that the zebrafish ar is required for spermatogenesis and maintenance of ovarian function, which confirms evolutionarily conserved functions of ar in vertebrates, as well as indicates that ar-null zebrafish are a suitable model for studying pathologic mechanisms related to androgen disorders.