Altered expression of genes involved in regulation of vitamin A metabolism, solute transportation, and cytoskeletal function in the androgen-insensitive Tfm mouse testis
Altered expression of genes involved in regulation of vitamin A metabolism, solute transportation, and cytoskeletal function in the androgen-insensitive Tfm mouse testis
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DOI：
10.1210/en.2006-1412
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发表时间：
2007-06-01
期刊：
影响因子：
4.8
通讯作者：
Baker, P. J.
中科院分区：
文献类型：
--
作者：
O'Shaughnessy, P. J.;Abel, M.;Baker, P. J.
雄激素对精子发生的发育和维持至关重要，但雄激素在睾丸中作用的潜在机制仍不清楚。为了帮助阐明这些机制，在青春期（20日龄）、雄激素不敏感的睾丸雌性化（Tfm）小鼠和正常对照小鼠的睾丸中测量基因表达。使用微阵列（Affyssin芯片430 A和430 B），初始数据鉴定了大量在Tfm睾丸中下调的基因（> 4700）。这些基因主要是生殖细胞起源，反映了逮捕的精子发生，这是明显的20日龄TFM睾丸。随后的体外筛选和在此基因集的计算机识别出20个基因的体细胞管状起源，显着下调的Tfm睾丸和6个基因，显着上调。通过实时PCR证实了这些基因的表达改变，并且在Tfm睾丸中下调的基因在用雄激素治疗的性腺功能减退（hpg）小鼠的睾丸中显示出上调。在一项使用实时PCR的发育研究中，大多数调控基因在胎儿和新生儿发育过程中表现出正常表达，仅在10至20 d之间偏离对照。在所有情况下，表达在成年中也减少，尽管由于成年Tfm小鼠中固有的隐睾症，解释更复杂。在Tfm睾丸中显示差异表达的体细胞基因总数中，50%与三个独立的基因组相关，这些基因参与调节维生素A代谢、溶质转运和细胞骨架功能。因此，雄激素对肾小管功能和精子发生的影响可能部分通过调节肾小管环境和控制视黄酸浓度来介导。
Androgens are essential for the development and maintenance of spermatogenesis, but the underlying mechanisms of androgen action in the testis remain unclear. To help clarify these mechanisms, gene expression was measured in testes of pubertal (20 d old), androgen- insensitive, testicular feminized (Tfm) mice and in normal controls. Using microarrays (Affymetrix chips 430A and 430B), initial data identified a large number of genes down- regulated in the Tfm testis (> 4700). These genes were largely of germ cell origin, reflecting the arrest of spermatogenesis that is apparent in the 20-d-old Tfm testis. Subsequent screening in vitro and in silico of this gene set identified 20 genes of a somatic tubular origin that were significantly down-regulated in the Tfm testis and six genes that were significantly up-regulated. Altered expression of these genes was confirmed by real-time PCR, and genes down-regulated in the Tfm testis were shown to be up-regulated in testes of hypogonadal (hpg) mice treated with androgen. In a developmental study using real-time PCR most of the regulated genes showed normal expression during fetal and neonatal development and deviated from control only between 10 and 20 d. In all cases, expression was also reduced in the adult, although interpretation is more complex because of the inherent cryptorchidism in the adult Tfm mouse. Of the total number of somatic genes showing differential expression in the Tfm testis, 50% were associated with three separate groups of genes involved in regulation of vitamin A metabolism, solute transportation, and cytoskeletal function. Thus, effects of androgens on tubular function and spermatogenesis may be mediated in part through regulation of the tubular environment and control of retinoic acid concentrations.