Vizziano Denise, Baron Daniel, Randuineau Gwenaëlle, Mahè Sophie, Cauty Chantal, Guiguen Yann
Facultad de Ciencias, Oceanología, Montevideo 11400, Uruguay.
Biol Reprod. 2008 May;78(5):939-46. doi: 10.1095/biolreprod.107.065961. Epub 2008 Jan 16.
The present study was designed to obtain new insights into fish gonadal sex differentiation by comparing the effects of two different masculinizing treatments on some candidate gene expression profiles. Masculinization was induced in rainbow trout, Oncorhynchus mykiss, genetic all-female populations using either an active fish androgen (11betaAnd, 11beta-hydroxyandrostenedione) or an aromatase inhibitor (ATD, 1,4,6-androstatriene-3,17-dione). The expression profiles of 100 candidate genes were obtained by real-time RT-PCR, and 46 profiles displayed a significant differential expression between control populations (males and females) and ATD/11betaAnd-treated populations. These expression profiles were grouped in four temporally correlated expression clusters. Among the common responses shared by the two masculinizing treatments, the inhibition of some early female differentiating genes (cyp19a1, foxl2a, fst, and fshb) appears to be crucial for effective masculinization, suggesting that these genes act together via a short regulation loop to maintain high sex-specific ovarian expression of cyp19a1. This simultaneous down-regulation of female-specific genes could be triggered by some testicular genes, such as dmrt1, nr0b1 (also known as dax1), and pdgfra, which are quickly up-regulated by the two masculinizing treatments. In contrast to 11betaAnd, ATD quickly restored the expression levels of steroidogenesis related genes (cyp11b2.1, cyp11b2.2, hsd3b1, cyp17a, star, and nr5a1) and some Sertoli cell markers (sox9a2 and amh) to the expression levels observed during control testicular differentiation. This demonstrates that these genes are probably not needed for active masculinization and that the inhibition of endogenous estrogen synthesis produces a much more complete and specific testicular pattern of gene expression than that observed following androgen-induced masculinization.
本研究旨在通过比较两种不同的雄性化处理对一些候选基因表达谱的影响，获得对鱼类性腺性别分化的新见解。使用活性鱼类雄激素（11βAnd，11β-羟基雄烯二酮）或芳香化酶抑制剂（ATD，1,4,6-雄甾三烯-3,17-二酮）对虹鳟（Oncorhynchus mykiss）遗传全雌群体进行雄性化诱导。通过实时RT-PCR获得了100个候选基因的表达谱，其中46个表达谱在对照群体（雄性和雌性）与ATD/11βAnd处理群体之间显示出显著差异表达。这些表达谱被分为四个时间相关的表达簇。在两种雄性化处理共有的常见反应中，抑制一些早期雌性分化基因（cyp19a1、foxl2a、fst和fshb）似乎对有效的雄性化至关重要，这表明这些基因通过一个短调控环共同作用以维持cyp19a1的高性别特异性卵巢表达。雌性特异性基因的这种同时下调可能由一些睾丸基因触发，如dmrt1、nr0b1（也称为dax1）和pdgfra，这两种雄性化处理会使其迅速上调。与11βAnd不同，ATD迅速将类固醇生成相关基因（cyp11b2.1、cyp11b2.2、hsd3b1、cyp17a、star和nr5a1）以及一些支持细胞标记物（sox9a2和amh）的表达水平恢复到对照睾丸分化期间观察到的表达水平。这表明这些基因可能不是活性雄性化所必需的，并且内源性雌激素合成的抑制产生了比雄激素诱导的雄性化后观察到的更完整和特异的睾丸基因表达模式。
