Expression profiling of candidate genes during ovary-to-testis trans-differentiation in rainbow trout masculinized by androgens

Expression profiling of candidate genes during ovary-to-testis trans-differentiation in rainbow trout masculinized by androgens
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DOI:
10.1016/j.ygcen.2008.01.016
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发表时间:
2008-04-01
影响因子:
2.7
通讯作者:
Guiguen, Yann
Guiguen, Yann
中科院分区:
医学3区
文献类型:
--
作者:
Baron, Daniel;Houlgatte, Remi;Guiguen, Yann

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鱼类性腺表型对性类固醇激素非常敏感,大多数鱼类可以通过雄激素处理获得功能性雄性化。为了深入了解雄激素诱导的雄性化的分子效应,我们的特点,在虹鳟鱼,性腺表达谱的103个候选基因参与性别分化和早期配子发生。雄激素治疗(11 P-羟基雄烯二酮,10 mg/kg食物,持续3个月)在遗传全雌性群体中施用。在不同的时间点,在遗传的所有男性和所有女性的对照群体和雄激素治疗组的性腺进行采样。通过实时RT-PCR记录基因表达谱,并使用全局聚类分析比较生物样品和基因表达。该分析显示,雄激素的雄性化作用首先通过抑制颗粒细胞相关基因,包括参与卵巢分化的基因(foxl 2a,fst,cyp 19 a1 a),随后通过抑制早期卵子发生的重要基因(gdj 9,bcl 2lb,fancl,gcl,fshb,lhb,sox 23,sox 24,nup 62和vtgr)。然而,这种雄性化处理并没有诱导与对照雄性群体中观察到的类似的睾丸分化。这一点对于许多睾丸间质细胞基因尤其明显,这些基因编码的蛋白质参与类固醇生成或其控制(hsd 3b 1、星星、cyp 17 a1、cyp 11 b2.1和nr 5a 1 b),在雄激素处理组中下调。伴随着一些支持细胞标记基因上调雄激素治疗(sox9a.1,nr 0 b1,cldn 11,dmrt 1),而其他下调(amh,sox9a.2),表明部分分化的支持细胞谱系。总的来说,这表明这个雄性化过程的关键步骤是颗粒细胞的去分化。(C)2008年爱思唯尔公司All rights reserved.
Fish gonadal phenotype is very sensitive to sex steroid and functional masculinizations can be obtained in most species using androgen treatments. To gain insight into the molecular effects of androgen-induced masculinization we characterized, in the rainbow trout, the gonadal expression profiles of 103 candidate genes involved in sex differentiation and early gametogenesis. The androgen treatment (I I P-hydroxyandrostenedione, 10 mg/kg of food for 3 months) was administered in a genetic all-female population. Gonads were sampled at different time points in genetic all-male and all-female control populations and in the androgen-treated group. Gene expression profiles were recorded by real-time RT-PCR and biological samples and gene expressions were compared using a global clustering analysis. This analysis revealed that masculinization with androgens acts firstly by repressing granulosa cell related genes, including genes involved in ovarian differentiation (foxl2a, fst, cyp19a1a), and subsequently by repressing genes important for early oogenesis (gdj9, bcl2lb, fancl, gcl, fshb, lhb, sox23, sox24, nup62 and vtgr). However, this masculinizing treatment did not induce a testicular differentiation similar to what was observed in the control male population. This was especially noticeable for many Leydig cell genes encoding proteins involved in steroidogenesis or its control (hsd3b1, star, cyp17a1, cyp11b2.1 and nr5a1b) that were down-regulated in the androgen-treated group. Concomitantly some Sertoli cells marker genes were up-regulated by the androgen treatment (sox9a.1, nr0b1, cldn11, dmrt1) whereas others were down-regulated (amh, sox9a.2), suggesting a partial differentiation of the Sertoli cell lineage. Overall, this suggests that the crucial step of this masculinization process is the de-differentiation of the granulosa cells. (C) 2008 Elsevier Inc. All rights reserved.