From the Farm to the Lab: How Chicken Embryos Contribute to the Field of Teratology.

Gabriela Elis Wachholz,Neil Vargesson,Bruna Duarte Rengel,Lucas Rosa Fraga

doi:10.3389/fgene.2021.666726

Abstract

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 in vivo, 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.

Highlights

In humans, data regarding congenital anomalies (CA) induced by teratogens are from observational studies, in which case reports and epidemiological studies indicate an increase of the rate of some malformation and potential risk factors
This review aims to highlight the role of the chicken embryo as an experimental model for studies in teratology
The chicken embryo model allows live and in ovo studies and analyses throughout development to define and evaluate potential risks of compounds, determine teratogenic phenotypes and understand and describe the mechanism involved in its teratogenic process

Summary

Introduction

Data regarding congenital anomalies (CA) induced by teratogens are from observational studies, in which case reports and epidemiological studies indicate an increase of the rate of some malformation and potential risk factors. Due to the fact that CA can cause infant and childhood death, illness and disabilities, it is important to have such methods to allow further investigation of their causes, risk factors and mechanisms [World Health Organization (WHO), 2020a] Such investigations help directly in the development of strategies to prevent further occurrence, therapeutic interventions and deaths from CAs. Nowadays many tools and approaches are utilized to study the causes and mechanisms that underlie a CA, from a range of cell culture assays to multiple animal and embryo models. The chicken embryo has the advantage of allowing easy administration of chemicals, compounds, external agents that may or are alleged to cause CA to determine their actions upon the embryo This allows the study of such CA and enables multiple analyses, genetic and morphological, to be performed in order to understand how the CA was caused and shed light on therapeutic strategies as well as how they could be prevented

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