Stress- and xenobiotic-induced changes in early fish embryo gene expression patterns as biomarkers of development and growth in juveniles

脊椎动物卵母细胞的细胞质在调节或修改由卵母细胞发育的胚胎的早期基因表达方面起着关键作用，并且可以影响胚胎后阶段的表型。尽管数十年来对哺乳动物的深入研究导致了生殖生物技术的发展，如体外受精（IVF），但对卵质因子的表观遗传影响仍然知之甚少；体外受精衍生的哺乳动物胚胎的胚胎畸形率仍然很高。我们对卵浆在鱼类早期个体发育中的作用知之甚少，但由于大多数鱼类的胚胎完全依赖于蛋黄中的营养物质，因此卵浆的影响可能是显著的。此外，在鱼类卵巢成熟过程中，一些已知会破坏成年鱼内分泌生理的母体激素和污染物从母体血液转移到卵母细胞中；这种不受控制的生物活性激素和内分泌干扰化合物的传递可能通过作用于激素受体或抑制天然激素的清除而对胚胎的早期发育产生重大影响。我们建议研究应激激素皮质醇对早期胚胎发育过程中关键生长相关基因表达的影响；卵子皮质醇含量随母体血浆激素水平（以及应激水平）的变化而变化，但其对胚胎发育的作用尚不清楚。此外，我们建议研究两类内分泌干扰化合物，异种雌激素（双酚a）和肝芳烃受体（TCDD）激活剂对相同基因表达的影响。这些因素对急性应激反应的影响，以及生长相关基因的表达将在胚胎和早期幼体中进行研究。

The cytoplasm of the vertebrate oocyte plays a key role in regulating or modifying early gene expression by an embryo that develops from that oocyte, and can influence the phenotype of post-embryonic stages. Despite decades of intensive research in mammals leading to the development of reproductive biotechnologies such as in vitro fertilization (IVF) the epigenetic influences of the ooplasm factors are still poorly understood; embryo deformity rates in IVF-derived mammalian embryos remain high. Much less is known about the role of ooplasm in the early ontogeny of fishes, but since the embryo of most fish species is totally reliant on nutrients in the egg yolk, the influence of the ooplasm is likely to be significant. Moreover, some maternal hormones and some contaminants that are known to disrupt endocrine physiology in adult fish are transferred from maternal blood to the oocytes during the maturation of fish ovaries; this uncontrolled delivery of biologically active hormones and endocrine disrupting compounds may have significant consequences for the early development of the embryo either by acting on hormone receptors, or by inhibiting the clearance of native hormones. We propose to examine the impact of the stress hormone, cortisol, on the expression of key growth-related genes during early embryogenesis; egg cortisol content varies with the maternal plasma hormone levels (and hence stress levels) of the brood-stock, but its actions on embryo development is poorly understood. In addition, we propose to examine the effect of two classes of endocrine disrupting compounds, a xenoestrogen (bisphenol A) and an activator of the hepatic aryl hydrocarbon receptor (TCDD) on the expression of the same genes. The effects of these factors on the acute stress-response, and the expression of growth related genes will be examined in embryos and early stage juveniles.