Nesan Dinushan, Vijayan Mathilakath M
Department of Biology, University of Waterloo, Waterloo, Ontario, N2L 3G1 Canada.
Sci Rep. 2016 Mar 4;6:22582. doi: 10.1038/srep22582.
In zebrafish (Danio rerio), de novo synthesis of cortisol in response to stressor exposure commences only after hatch. Maternally deposited cortisol is present during embryogenesis, but a role for this steroid in early development is unclear. We tested the hypothesis that maternal cortisol is essential for the proper development of hypothalamus-pituitary-interrenal (HPI) axis activity and the onset of the stressor-induced cortisol response in larval zebrafish. In this study, zygotic cortisol content was manipulated by microinjecting antibody to sequester this steroid, thereby making it unavailable during embryogenesis. This was compared with embryos containing excess cortisol by microinjection of exogenous steroid. The resulting larval phenotypes revealed distinct treatment effects, including deformed mesoderm structures when maternal cortisol was unavailable and cardiac edema after excess cortisol. Maternal cortisol unavailability heightened the cortisol stress response in post-hatch larvae, whereas excess cortisol abolished the stressor-mediated cortisol elevation. This contrasting hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had excess cortisol. These findings for the first time underscore a critical role for maternally deposited cortisol in programming HPI axis development and function in zebrafish.
在斑马鱼（Danio rerio）中，对应激源暴露的皮质醇从头合成仅在孵化后开始。胚胎发育期间存在母体沉积的皮质醇，但这种类固醇在早期发育中的作用尚不清楚。我们测试了这样一个假设，即母体皮质醇对于幼体斑马鱼下丘脑 - 垂体 - 肾间（HPI）轴活动的正常发育以及应激源诱导的皮质醇反应的启动至关重要。在本研究中，通过显微注射抗体来螯合这种类固醇，从而在胚胎发育期间使其无法利用，以此来操纵合子皮质醇含量。将其与通过显微注射外源类固醇而含有过量皮质醇的胚胎进行比较。所产生的幼体表型显示出不同的处理效果，包括母体皮质醇无法利用时中胚层结构畸形以及皮质醇过量时出现心脏水肿。母体皮质醇无法利用会增强孵化后幼体的皮质醇应激反应，而皮质醇过量则会消除应激源介导的皮质醇升高。这种相反的激素反应与关键HPI轴基因（包括crf、11B羟化酶、pomca和star）表达的改变相对应，这些基因在皮质醇可用性降低时上调，而在胚胎皮质醇过量时下调。这些发现首次强调了母体沉积的皮质醇在斑马鱼HPI轴发育和功能编程中的关键作用。
