Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago P.C. 8360160, Chile.
Mol Hum Reprod. 2011 Dec;17(12):739-46. doi: 10.1093/molehr/gar051. Epub 2011 Jul 20.
DAX-1 [dosage-sensitive sex reversal-adrenal hypoplasia congenital (AHC) critical region on the X chromosome gene 1; NR0B1] is an orphan nuclear receptor that acts as a transcriptional repressor in adrenal/gonadal development, steroidogenesis and probably spermatogenesis. An alternatively spliced form called DAX-1A (NR0B1A) has been described in several tissues including the testis, and in vitro studies have shown an inhibitory effect on DAX-1 transcriptional function. We aimed to study the mRNA and protein expression of DAX-1 in testicular tissues of 65 men with primary spermatogenic failure [complete Sertoli cell only syndrome (SCOS), focal SCOS, maturation arrest and mixed atrophy] compared with 33 controls with normal spermatogenesis. As a novel finding, we observed intense immunostaining, not only in the nucleus of Sertoli cells, but also in pachytene spermatocytes and round spermatids. The quantitative mRNA expression of DAX-1 and DAX-1A was similar between cases and controls and was not associated with the levels of gonadotrophins and steroids. Moreover, DAX-I transcript expression level was ∼750-fold higher than DAX-1A, and there was a strong positive correlation between them (r = 0.52; P< 0.001). We conclude that, in addition to Sertoli cells, DAX-1/DAX-1A is expressed in germ cells from spermatogonia to round spermatids. Besides, the similar mRNA expression of DAX-I and DAX-IA in testicular tissues from cases and controls does not support the involvement of DAX-1 in the etiology of primary spermatogenic failure. Finally, the low level of expression of the alternative transcriptional variant DAX-1A would not support its putative inhibitory function in vivo.
DAX-1 [剂量敏感性别逆转-肾上腺发育不全先天性（AHC）X 染色体基因 1 关键区域；NR0B1] 是一种孤儿核受体，在肾上腺/性腺发育、类固醇生成中起转录抑制因子作用，可能在精子发生中也起作用。已经在包括睾丸在内的几种组织中描述了一种称为 DAX-1A（NR0B1A）的选择性剪接形式，体外研究表明其对 DAX-1 转录功能具有抑制作用。我们旨在研究 65 例原发性精子发生衰竭患者[完全 Sertoli 细胞仅综合征（SCOS）、局灶性 SCOS、成熟阻滞和混合萎缩]睾丸组织中 DAX-1 的 mRNA 和蛋白表达情况，并与 33 例正常精子发生的对照进行比较。作为一个新发现，我们观察到不仅在 Sertoli 细胞的核中，而且在粗线期精母细胞和圆形精子中也有强烈的免疫染色。DAX-1 和 DAX-1A 的定量 mRNA 表达在病例和对照组之间相似，与促性腺激素和类固醇水平无关。此外，DAX-1 转录物的表达水平比 DAX-1A 高约 750 倍，并且它们之间存在强烈的正相关（r = 0.52；P<0.001）。我们得出结论，除了 Sertoli 细胞外，DAX-1/DAX-1A 在精原细胞到圆形精子细胞的生殖细胞中表达。此外，病例和对照组睾丸组织中 DAX-1 和 DAX-1A 的相似 mRNA 表达不支持 DAX-1 参与原发性精子发生衰竭的病因。最后，替代转录变体 DAX-1A 的低表达水平不支持其在体内的潜在抑制功能。
