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

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.

Toxicity Study of Chlorzoxazone and Isosorbide Dinitrate using Chick Embryo

“…Apart from being cheap and easy availability, chicken embryo can reveal detrimental effects and thus, not to be followed up in rats, this can help to minimize the number of mice necessary in preliminary drug screening and also can provide some insight into probable mechanisms of action of the medication as well as safety. 9 Chlorzoxazone is a muscle relaxant drug that can be used relieve abdominal muscle cramps which is the common symptom in pregnancy. Data available from animal experiments as well as human studies indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex involved in producing and maintaining skeletal muscle spasm of varied etiology.…”

Bridging the In Vitro to In Vivo gap: Using the Chick Embryo Model to Accelerate Nanoparticle Validation and Qualification for In Vivo studies

“…Each method has advantages; the in ovo method increases survival and facilitates the natural calcium exchange from the shell, while the ex ovo method allows greater access to the embryo, increasing the applicable imaging modalities . Due the ability to directly observe its development and rapid developmental timeline, the CE has been invaluable historically for studies of embryo and organ development, including neural, limb, and cardiac development. − These same features make the CE a common model for studying the adverse effects of drugs, viruses, and compounds . For example, the CE has been used to evaluate the teratology of thalidomide, the Zika virus, and fetal alcohol syndrome disorders. , Beyond developmental studies, the CE model facilitates rapid assessment of drugs delivered topically, vascularly, or directly into the body of the embryo or into the yolk sac and amnion. , Analyses of drug behavior include embryo mortality, egg/embryo weight, developmental alterations, serum biomarkers, biodistribution to organs, and histopathology of organs. − The CE model has also been used for studying infection and virulence of bacteria and fungus. − Infection and virulence were assessed via embryonal death, a histological assessment of organs, a reverse transcription-polymerase chain reaction (RT-PCR) for alterations in chemokines and cytokines, and an enzyme-linked immunoassay (ELISA) for antibody production. − , …”

Exploring the Expression and Function of cTyro3, a Candidate Zika Virus Receptor, in the Embryonic Chicken Brain and Inner Ear

“…Therefore, to investigate the role of TAM receptors in ZIKV entry, we have used the embryonic chick model as our in vivo system. This system offers easy manipulation of experimental factors, a low biohazard risk, and a medium-throughput analysis of the results [ 60 ]. We recently used this model organism to show that ZIKV can infect both the neural tube and inner ears [ 41 ], with permissivity of the latter tissue possibly relevant to an increased incidence of hearing loss following in utero exposure to ZIKV in humans [ 12 , 41 ].…”