Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China.
Biol Reprod. 2012 Sep 7;87(3):54. doi: 10.1095/biolreprod.112.099689. Print 2012 Sep.
Follistatin 1 (Fst1) is a binding protein of activin and some other members of the transforming growth factor beta superfamily. It plays a key role in the regulation of gonadal function in vertebrates. An oocyte-specific promoter, derived from the zona pellucida 3 (zp3) gene, was used to create transgenic fst1 zebrafish (Danio rerio). Three independent oocyte-specific overexpression fst1 transgenic zebrafish lines were generated. Decreased levels of phosphorylated Smad3 were observed in ovarian tissues in fst1 transgenic fish compared with those from their control female siblings. Analyses on the numbers of mature eggs also indicated the attenuated oocyte maturation in the fst1 transgenic fish and in the females administered recombinant human Fst protein. Remarkably, when raised in the same tank with their control siblings, a significantly larger proportion of the fst1 transgenic population developed as males compared to the controls. Moreover, assessing the levels of active caspase 3 in gonadal tissues at 30 days postfertilization, we observed increased levels of apoptosis in the transitioning gonads of the transgenic fish compared to nontransgenic control siblings. Our results demonstrate that zebrafish Fst1 not only acts as an inhibitory binding protein of activin in the regulation of oocyte maturation in adult females but also plays a potential role in the masculinization of juveniles. Overall, the present study contributes to our understanding of the paracrine roles of fst1 as well as normal oocyte maturation and gonadal differentiation.
卵泡抑素 1（Follistatin 1，Fst1）是激活素和转化生长因子-β超家族其他成员的结合蛋白。它在脊椎动物性腺功能的调节中起着关键作用。本研究利用来自透明带 3（zona pellucida 3，zp3）基因的卵母细胞特异性启动子，构建了 Fst1 转基因斑马鱼（Danio rerio）。获得了 3 条独立的卵母细胞特异性过表达 Fst1 转基因斑马鱼系。与对照组雌性个体相比，Fst1 转基因鱼的卵巢组织中磷酸化 Smad3 水平降低。分析成熟卵母细胞的数量也表明 Fst1 转基因鱼和接受重组人 Fst 蛋白处理的雌性个体的卵母细胞成熟受到抑制。值得注意的是，当与对照组个体一起饲养时，Fst1 转基因群体中发育为雄性的比例显著高于对照组。此外，在受精后 30 天评估性腺组织中活性 caspase 3 的水平时，我们观察到转基因鱼的过渡性腺组织中的细胞凋亡水平高于非转基因对照组。我们的研究结果表明，斑马鱼 Fst1 不仅作为激活素的抑制性结合蛋白在调节成年雌性个体的卵母细胞成熟中起作用，而且在幼鱼的雄性化过程中也发挥潜在作用。总的来说，本研究有助于我们理解 fst1 的旁分泌作用以及正常卵母细胞成熟和性腺分化。
