Wachholz Gabriela Elis, Rengel Bruna Duarte, Vargesson Neil, Fraga Lucas Rosa
Postgraduate Program of Genetics and Molecular Biology, Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Laboratory of Genomic Medicine, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Front Genet. 2021 Jul 22;12:666726. doi: 10.3389/fgene.2021.666726. eCollection 2021.
Congenital anomalies and its causes, particularly, by external factors are the aim of the field called teratology. The external factors studied by teratology are known as teratogens and can be biological or environmental factors for example, chemicals, medications, recreational drugs, environmental pollutants, physical agents (e.g., X-rays and maternal hyperthermia) and maternal metabolic conditions. Proving the teratogenicity of a factor is a difficult task requiring epidemiology studies as well as experimental teratology evidence from the use of animal models, one of which is the chicken embryo. This model in particular has the advantage of being able to follow development live and , with rapid development hatching around 21 days, is cheap and easy to manipulate and to observe development. All this allows the chicken embryo to be used in drug screening studies, teratogenic evaluation and studies of mechanisms of teratogenicity. The chicken embryo shares morphological, biochemical and genetic similarities with humans as well as mammalian species, making them ideal to ascertain the actions of teratogens, as well as screen drugs to test for their safety. Pre-clinical trials for new drugs are carried out in rodents and rabbits, however, chicken embryos have been used to screen new compounds or analogs of thalidomide as well as to investigate how some drugs can lead to congenital malformations. Indeed, the chicken embryo has proved valuable in understanding how many congenital anomalies, seen in humans, arise following teratogen exposure. The aim of this review is to highlight the role of the chicken embryo as an experimental model for studies in teratology, exploring its use in drug screening studies, phenotypic evaluation and studies of teratogenic mechanisms of action. Here, we discuss many known teratogens, that have been evaluated using the chicken embryo model including some medicines, such as, thalidomide, valproic acid; recreational drugs including alcohol; environmental influences, such as viruses, specifically ZIKV, which is a newly discovered human teratogen. In addition, we discuss how the chicken embryo has provided insight on the mechanisms of teratogenesis of many compounds and also how this impact on drug safety.
先天性异常及其病因，尤其是外部因素导致的先天性异常，是致畸学领域的研究目标。致畸学所研究的外部因素被称为致畸原，它们可以是生物因素或环境因素，例如化学物质、药物、消遣性毒品、环境污染物、物理因子（如X射线和母体体温过高）以及母体代谢状况。证明一个因素具有致畸性是一项艰巨的任务，需要进行流行病学研究以及来自动物模型（其中之一是鸡胚）使用的实验致畸学证据。这个模型尤其具有能够实时追踪发育过程的优势，并且由于其发育迅速，大约21天孵化，成本低廉且易于操作和观察发育情况。所有这些使得鸡胚能够用于药物筛选研究、致畸性评估以及致畸机制研究。鸡胚在形态、生化和遗传方面与人类以及哺乳动物物种具有相似性，这使其成为确定致畸原作用以及筛选药物安全性的理想选择。新药的临床前试验在啮齿动物和兔子身上进行，然而，鸡胚已被用于筛选沙利度胺的新化合物或类似物，以及研究某些药物如何导致先天性畸形。事实上，鸡胚已被证明在理解人类中观察到的许多先天性异常是如何在接触致畸原后产生方面具有重要价值。本综述的目的是强调鸡胚作为致畸学研究实验模型的作用，探讨其在药物筛选研究、表型评估以及致畸作用机制研究中的应用。在此，我们讨论了许多已使用鸡胚模型进行评估的已知致畸原，包括一些药物，如沙利度胺、丙戊酸；消遣性毒品，包括酒精；环境影响因素，如病毒，特别是寨卡病毒，它是一种新发现的人类致畸原。此外，我们还讨论了鸡胚如何为许多化合物的致畸机制提供了见解，以及这对药物安全性的影响。
