CHICK EMBRYO MODEL IN DEVELOPMENTAL TOXICITY STUDIES

Year 2025, Volume: 16 Issue: 2, 43 - 52, 31.08.2025

Muhammed Hasan Şirin , Ayhan Filazi

https://doi.org/10.38137/vftd.1609269

Abstract

Teratology, which examines congenital anomalies and the factors that cause these anomalies, is a scientific discipline that intersects with developmental toxicology. The evaluation of the potential effects of teratogens on foetal development has become a fundamental prerequisite of preclinical research, particularly in revealing how environmental and chemical factors encountered during the prenatal period affect embryonic development. The chicken embryo model has long been utilized in developmental toxicity research. Among the methods used in preclinical studies, the chicken embryo model offers significant advantages compared to other animal models due to its easy accessibility, low cost, and fewer ethical restrictions.Additionally, the rapid observation of embryonic development represents a key advantage of this model. Moreover, the ability to perform analyses in a controlled environment has established the chicken embryo model as an indispensable tool in scientific studies. With its remarkable similarities to human embryonic development, the chicken embryo model continues to be a powerful tool for understanding embryonic developmental processes. This review aims to emphasize the advantages and limitations of utilizing chicken embryonic models in developmental toxicity testing.

Keywords

Teratogenicity , Embryotoxicity , Developmental toxicology , In ovo , Chick embryo

GELİŞİMSEL TOKSİSİTE ÇALIŞMALARINDA CİVCİV EMBRİYO MODELİ

Abstract

Doğumsal anomalileri ve bu anomalilere neden olan faktörleri inceleyen teratoloji, gelişimsel toksikoloji ile kesişen bir bilim dalıdır. Teratojenlerin fetal gelişim üzerindeki potansiyel etkilerinin değerlendirilmesi özellikle doğum öncesi dönemlerde karşılaşılan çevresel ve kimyasal faktörlerin embriyonik gelişime nasıl etki ettiğini ortaya koymak klinik öncesi araştırmaların temel ön koşullarından biri haline gelmiştir. Tavuk embriyosu, gelişimsel toksisite araştırmaları için uzun zamandır kullanılan bir modeldir. Klinik öncesi araştırmalarda kullanılan yöntemler arasında kolay erişilebilirliği, düşük maliyeti ve etik açıdan daha az sınırlayıcı olması nedeniyle diğer hayvan modellerine kıyasla önemli avantajlar sunmaktadır. Ayrıca, Embriyonik gelişimin hızla gözlemlenebilmesi, bu modelin önemli bir avantajıdır. Aynı zamanda analizlerin kontrollü bir ortamda gerçekleştirilebilmesi, civciv embriyo modelini bilimsel çalışmalarda vazgeçilmez bir araç haline getirmiştir. İnsan embriyonik gelişimiyle dikkate değer benzerlikler taşıyan civciv embriyo modeli, embriyonik gelişim süreçlerini anlamak için güçlü bir araç olmaya devam etmektedir. Bu inceleme, gelişimsel toksisite testinde civciv embriyonik modellerinin kullanımını ele alarak avantajlarını ve dezavantajlarını vurgulamayı amaçlamaktadır.

Keywords

Teratojenite , Embriyotoksisite , Gelişimsel toksikoloji , İn ovo , civciv embriyosu

References

• Abdelaziz, K., Helmy, Y. A., Yitbarek, A., Hodgins, D. C., Sharafeldin, T. A. & Selim, M. S. (2024). Advances in Poultry Vaccines: Leveraging Biotechnology for Improving Vaccine Development, Stability, and Delivery. Vaccines, 12(2), 134.
• Acharya, B., Dey, S., Sahu, P. K., Behera, A., Chowdhury, B. & Behera, S. (2024). Perspectives on chick embryo models in developmental and reproductive toxicity screening. Reproductive Toxicology, 126, 108583.
• Ainsworth, S. J., Stanley, R. L. & Evans, D. J. (2010). Developmental stages of the Japanese quail. Journal of Anatomy, 216(1), 3-15.
• Beedie, S. L., Diamond, A. J., Fraga, L. R., Figg, W. D. & Vargesson, N. (2017). Vertebrate embryos as tools for anti-angiogenic drug screening and function. Reproductive Toxicology, 70, 49-59.
• Bellairs, R. & Osmond, M. (2005). Atlas of chick development, Elsevier.
• Bellairs, R. & Osmond, M. (2014). Chapter 3 - Early Stages. In: Atlas of Chick Development (Third Edition). Eds: Bellairs R, Osmond M. Boston: Academic Press, p. 15-28.
• Brent, R. L. (2004). Environmental causes of human congenital malformations: the pediatrician’s role in dealing with these complex clinical problems caused by a multiplicity of environmental and genetic factors. Pediatrics, 113, Supplement 3, 957-968.
• Chen, L., Wang, S., Feng, Y., Zhang, J., Du, Y, Zhang, J., Van Ongeval, C., Ni, Y. & Li, Y. (2021). Utilisation of chick embryo chorioallantoic membrane as a model platform for imaging-navigated biomedical research. Cells, 10(2), 463.
• Chung, D. D., Pinson, M. R., Bhenderu, L. S., Lai, M. S., Patel, R. A. & Miranda, R. C. (2021). Toxic and teratogenic effects of prenatal alcohol exposure on fetal development, adolescence, and adulthood. International Journal of Molecular Sciences, 22(16), 8785.
• Crespo, P. & Casar, B. (2016). The chick embryo chorioallantoic membrane as an in vivo model to study metastasis. Bio-Protocol, 6(20), e1962-e.
• Çakır, E. B. (2024). In ovo injection of testosterone to yolk sac modulates early posthatching development and physiology of male chick in broilers. Poultry Science, 103(3), 103389.
• Das, R., Mishra, P. & Jha R. (2021). In ovo feeding as a tool for improving performance and gut health of poultry: a review. Frontiers in Veterinary Science, 8, 754246.
• Davey, M. G., Towers, M., Vargesson, N. & Tickle, C. (2018). The chick limb: embryology, genetics and teratology. International Journal of Developmental Biology, 62(1-2-3),85-95.
• Dhayer, M., Jordao, A., Dekiouk, S., Cleret, D., Germain, N. & Marchetti, P. (2024). Implementing Chicken Chorioallantoic Membrane (CAM) Assays for Validating Biomaterials in Tissue Engineering: Rationale and Methods. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 112(11), e35496.
• Dooley, M., Peebles, E., Zhai, W., Mejia, L., Zumwalt, C. & Corzo, A. (2011). Effects of L-carnitine via in ovo injection with or without L-carnitine feed supplementation on broiler hatchability and posthatch performance. Journal of Applied Poultry Research, 20(4), 491-497.
• Fischer, D., Fluegen, G., Garcia, P., Ghaffari-Tabrizi-Wizsy, N., Gribaldo, L., Huang, R. Y. J, Rasche, V., Ribatti, D., Rousset, X. & Pinto, M. T. (2022). The CAM model—Q&A with experts. Cancers, 15(1), 191.
• Flentke, G. R. & Smith, S. M. (2018). The avian embryo as a model for fetal alcohol spectrum disorder. Biochemistry and Cell Biology, 96(2), 98-106.
• Fonseca, B. B., da Silva, M. V. & de Morais Ribeiro, L. N. (2021). The chicken embryo as an in vivo experimental model for drug testing: Advantages and limitations. Lab Animal, 50(6), 138-139.
• Fraga, L. R., de Oliveira, M. R., Wermann, K. M. & Vargesson, N. (2024). Assessment of the Teratogenic Effect of Drugs on the Chicken Embryo. In: Teratogenicity Testing: Methods and Protocols. Eds: Springer, p. 251-60.
• Fraga, L. R., Vianna, F. S. L., Del Campo, M., Sanseverino, M. T. V. & Schuler-Faccini, L. (2022). Teratogenesis: Experimental Models, Mechanisms and Clinical Findings in Humans. Frontiers Media SA, 13, 901400.
• Gomes, J. A. , Olstad, E. W. , Kowalski, T. W. , Gervin, K. , Vianna, F. S. L., Schüler-Faccini, L. & Nordeng, H. M. E. (2021). Genetic susceptibility to drug teratogenicity: A systematic literature review. Frontiers in Genetics, 12, 645555.
• Grant, A., Ponia, S. S., Tripathi, S, Balasubramaniam, V., Miorin, L., Sourisseau, M., Schwarz, M. C., Sánchez-Seco, M. P., Evans, M. J. & Best, S. M. (2016). Zika virus targets human STAT2 to inhibit type I interferon signaling. Cell Host & Microbe, 19(6), 882-890.
• Hamburger, V. & Hamilton, H. L. (1951). A series of normal stages in the development of the chick embryo. Journal of Morphology, 88(1), 49-92.
• Janer, G., Slob, W., Hakkert, B. C., Vermeire, T. & Piersma, A. H. (2008). A retrospective analysis of developmental toxicity studies in rat and rabbit: what is the added value of the rabbit as an additional test species? Regulatory Toxicology and Pharmacology, 50(2), 206-217.
• Jiang, Q., Xu, X., Zhang, C., Luo, J., Lv, N., Shi, L., Ji, A., Gao, M., Chen, F. & Cui, L. (2020). In ovo very early-in-life exposure to diesel exhaust induced cardiopulmonary toxicity in a hatchling chick model. Environmental Pollution, 264, 114718.
• Kalter, H. (2003). Teratology in the 20th century Environmental causes of Congenital malformations in humans and how their environmental causes were established. Neurotoxicology and Teratology, 25(2), 131-282.
• Karagiozova, D. (2017). Teratogenic agents and related conditions. Texila Int J Med, 5(1), 12. Kemper, F. & Berger, H. (1962). Changes in the blood of chicks under the influence of thalidomide. Zeitschrift fur die Gesamte Experimentelle Medizin, 136, 86-96.
• Kue, C. S., Tan, K. Y., LaM, M. L. & Lee, H. B. (2015). Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs. Experimental Animals, 64(2), 129-138.
• Latchoumycandane, C., Jenardhanan, P. & Mathur, P. P. (2018). Environmental impact on gametogenesis and embryogenesis: an overview. 2nd edition, Volume 3.
• Malek, A. (2012). Effects of prenatal cocaine exposure on human pregnancy and postpartum. Pharmaceut Anal Acta, 3, 191.
• Meijerhof, R., Hulet, R. (1997). In ovo injection of competitive exclusion culture in broiler hatching eggs. Journal of Applied Poultry Research, 6(3), 260-266.
• Nguyen, T. T. T., Shahin, K., Allan, B., Sarfraz, M., Wheler, C., Gerdts, V., Köster, W. & Dar, A. (2022). Enhancement of protective efficacy of innate immunostimulant based formulations against yolk sac infection in young chicks. Poultry Science, 101(11), 102119.
• Nikolov, B., Georgieva, A., Manov, V. & Kril, A. (2014). In ovo tests for carcinogenicity, mutagenicity and embryotoxicity. Scientific Works. Series C. Veterinary Medicine. Vol. LX (1).
• Niloofar, A., Marek, B., Krzysztof, K. & Katarzyna, S. (2024). Emerging in ovo technologies in poultry production and the re-discovered chicken model in preclinical research. Physical Sciences Reviews, 9(2), 843-859.
• Nowak-Sliwinska, P., Segura, T. & Iruela-Arispe, M. L. (2014). The chicken chorioallantoic membrane model in biology, medicine and bioengineering. Angiogenesis, 17, 779-804.
• Özparlak, H. (2015). Tavuk Embriyolarinin Embriyotoksisite Ve Teratojenite Testlerinde Kullanimi. Selçuk Üniversitesi Fen Fakültesi Fen Dergisi, 40, 13-22.
• Öztürk, S. & Dayan, M. O. (2024). The embryotoxic and teratogenic effects of metamizole sodium. Anatomia, Histologia, Embryologia, 53(5), e13101.
• Paredes-Páliz, K., Armendáriz-Ramos, J., Salazar A. U. & Torres A. R. I. (2024). The most common teratogens as factors of mutability: A literature review. Salud Ciencia Y Tecnología, 4, 1098.
• Peebles, E. (2018). In ovo applications in poultry: a review. Poultry Science, 97(7), 2322-2338.
• Pintarasri, S., Plakornkul, V., Viravud, Y., Payuhakrit, W. & Rungruang, T. (2023). Folic Acid Attenuates MSG-Induced Teratogenicity during A 2-Month Pregnancy by Preventing Neural Crest Cell Destruction and Malformation in Chick Embryo Models. Trends in Sciences, 20(7), 6656.
• Prelusky, D. B., Hamilton R. M., Foster, B. C., Trenholm, L. H. & Thompson, B. K. (1987). Optimization of chick embryotoxicity bioassay for testing toxicity potential of fungal metabolites. Journal of the Association of Official Analytical Chemists, 70(6), 1049-1055.
• Rashidi, H. & Sottile, V. (2009). The chick embryo: hatching a model for contemporary biomedical research. Bioessays, 31(4), 459-465.
• Ribatti, D. (2016). The chick embryo chorioallantoic membrane (CAM). A multifaceted experimental model. Mechanisms of Development, 141, 70-77.
• Ribatti, D. & Annese, T. (2023). Chick embryo in experimental embryology and more. Pathology-Research and Practice, 245, 154478.
• Ribeiro, L., Schlemper, A., Da Silva, M. & Fonseca, B. (2022). Chicken embryo: a useful animal model for drug testing? European Review for Medical & Pharmacological Sciences, 26, 13.
• Roto, S. M., Kwon Y. M. & Ricke, S. C. (2016). Applications of in ovo technique for the optimal development of the gastrointestinal tract and the potential influence on the establishment of its microbiome in poultry. Frontiers in Veterinary Science, 3, 63.
• Saeed, M., Babazadeh, D., Naveed, M., Alagawany, M., Abd El‐Hack, M. E., Arain, M. A., Tiwari, R., Sachan, S., Karthik, K. & Dhama, K. (2019). In ovo delivery of various biological supplements, vaccines and drugs in poultry: current knowledge. Journal of the Science of Food and Agriculture, 99(8), 3727-3739.
• Sambu, S., Hemaram, U., Murugan, R. & Alsofi, A. A. (2022). Toxicological and Teratogenic Effect of Various Food Additives: An Updated Review. BioMed Research International, 1, 6829409.
• Sharma, J. & Burmester, B. (1982). Resistance of Marek's disease at hatching in chickens vaccinated as embryos with the turkey herpesvirus. Avian Diseases, 134-149.
• Smith, S. M., Flentke, G. R. & Garic, A. (2012). Avian models in teratology and developmental toxicology. Developmental Toxicology: Methods and Protocols, 85-103.
• Spohr, H. (2005). Teratogene Effekte von Nikotin, Drogen und Alkohol. Die Gynäkologie, 38(1), 25-32.
• Staton, C. A., Stribbling, S. M., Tazzyman, S. Hughes, R., Brown, N. J. & Lewis, C. E. (2004). Current methods for assaying angiogenesis in vitro and in vivo. International Journal of Experimental Pathology, 85(5), 233-248. Stern, C. D. (2004). The chick embryo-past, present and future as a model system in developmental biology. Mech Dev, 121(9), 1011-1013.
• Tainika, B. & Bayraktar, Ö. H. (2021). In ovo feeding technology: embryonic development, hatchability and hatching quality ofbroiler chicks. Turkish Journal of Veterinary & Animal Sciences, 45(5), 781-795.
• Tasharofi, S., Mohammadi, F., Amiri, N. & Nazem, M. (2018). Effects of intra‐yolk‐sac injection of dextrose and albumin on performance, jejunum morphology, liver and pectoral muscle glycogen and some serum metabolites of broilers. Journal of Animal Physiology and Animal Nutrition, 102(4), 917-923.
• Thawani, A., Sirohi, D., Kuhn, R. J. & Fekete, D. M. (2018). Zika virus can strongly infect and disrupt secondary organizers in the ventricular zone of the embryonic chicken brain. Cell Reports, 23(3), 692-700.
• Vargesson, N. (2013). Thalidomide embryopathy: an enigmatic challenge. International Scholarly Research Notices, 1, 241016.
• Vargesson, N. (2015). Thalidomide‐induced teratogenesis: History and mechanisms. Birth Defects Research Part C: Embryo Today: Reviews, 105(2), 140-156.
• Vargesson, N. (2019). The teratogenic effects of thalidomide on limbs. Journal of Hand Surgery (European Volume), 44(1), 88-95.
• Vargesson, N. & Fraga, L. (2017). Teratogenesis. eLS, 1-7.
• Wachholz, G. E., Rengel, B. D., Vargesson, N. & Fraga, L. R. (2021a). From the farm to the lab: how chicken embryos contribute to the field of teratology. Frontiers in Genetics, 12, 666726.
• Wachholz, G. E., Varela, A. P. M., Teixeira, T. F., de Matos, S. M. S., Rigon da Luz Soster, P., Vianna, F. S. L., de Souza, D. O. G., Roehe, P. M., Schuler‐Faccini, L. & Fraga, L. R. (2021b). Zika virus‐induced brain malformations in chicken embryos. Birth Defects Research, 113(1), 22-31.
• Wong, E. A. & Uni, Z. (2021). Centennial Review: The chicken yolk sac is a multifunctional organ. Poultry Science, 100(3), 100821.
• Yamamoto, J., Ito, T., Yamaguchi, Y. & Handa, H. (2022). Discovery of CRBN as a target of thalidomide: a breakthrough for progress in the development of protein degraders. Chemical Society Reviews, 51(15), 6234-6250.