Bablok Martin, Gellisch Morris, Scharf Marion, Brand-Saberi Beate, Morosan-Puopolo Gabriela
Department of Anatomy and Molecular Embryology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, Bochum, Germany.
Department of Anatomy and Molecular Embryology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, Bochum, Germany.
Ann Anat. 2023 Apr;247:152056. doi: 10.1016/j.aanat.2023.152056. Epub 2023 Jan 22.
Glucocorticoids - commonly known as stress hormones - belong to the family of steroid hormones and regulate numerous life essential physiological processes. As lipophilic molecules, glucocorticoids are known to cross the placental barrier in mammals, which - applied for therapeutic reasons or arising from environmental influences - illustrates the role of prenatal stress during embryonic developmental processes. The hormones employ their functions by binding to the glucocorticoid receptor (GR) and thus are involved in regulating the transcription of thousands of genes. Therefore, the aim of this study was to investigate the spatiotemporal expression pattern of the GR during early embryonic vertebrate development, using the chicken embryo as a model organism. The results should contribute to enhance and expand the current understanding of glucocorticoid signaling. By performing in-situ hybridization on whole mount chicken embryos from stage HH10 to HH29 and analyzing vibratome sections of hybridized embryos, we described the spatiotemporal expression pattern of the GR during early embryogenesis. Moreover, we compared the expression pattern of the GR with other developmental markers such as Pax7, Desmin, MyoD and HNK-1 using double in-situ hybridization and immunohistochemistry. We were able to determine the first emergence of GR expression in stage HH13 of chicken development in the cranial area, especially in the muscle anlagen of the branchial arches and of non-somitic neck muscles. Furthermore, we monitored the extension of GR expression pattern throughout later stages and found transcripts of GR during somitogenesis, limb development, myogenesis, neurulation and neural differentiation and moreover during organogenesis of the gastrointestinal organs, the heart, the kidneys and the lungs. Toward later stages, GR expression transitioned from more distinct areas of expression to an increasingly ubiquitous expression pattern. Our results support the notion of an enormous relevance of glucocorticoid signaling during vertebrate embryonic development and contribute to a better understanding of the consequences of prenatal stress and the clinical administration of prenatal glucocorticoids.
糖皮质激素——通常被称为应激激素——属于类固醇激素家族,调节众多生命必需的生理过程。作为亲脂性分子,糖皮质激素已知可穿过哺乳动物的胎盘屏障,这在出于治疗目的应用或受环境影响时,说明了产前应激在胚胎发育过程中的作用。这些激素通过与糖皮质激素受体(GR)结合来发挥其功能,从而参与调控数千个基因的转录。因此,本研究的目的是利用鸡胚作为模式生物,研究早期脊椎动物胚胎发育过程中GR的时空表达模式。研究结果应有助于加强和拓展目前对糖皮质激素信号传导的理解。通过对HH10至HH29阶段的鸡胚整体进行原位杂交,并分析杂交胚胎的振动切片,我们描述了早期胚胎发生过程中GR的时空表达模式。此外,我们使用双重原位杂交和免疫组织化学将GR的表达模式与其他发育标记物如Pax7、结蛋白、MyoD和HNK-1进行了比较。我们能够确定鸡发育的HH13阶段GR在颅区,特别是在鳃弓和非体节颈部肌肉的肌原基中首次出现表达。此外,我们监测了GR表达模式在后续阶段的扩展,发现在体节形成、肢体发育、肌发生、神经胚形成和神经分化过程中以及在胃肠道器官、心脏、肾脏和肺的器官发生过程中都有GR的转录本。在发育后期,GR的表达从更明显的表达区域转变为越来越普遍的表达模式。我们的研究结果支持了糖皮质激素信号传导在脊椎动物胚胎发育过程中具有巨大相关性的观点,并有助于更好地理解产前应激的后果以及产前糖皮质激素的临床应用。