Smooth Skin, Rough Start 

Vitamin A, also known as retinoic acid (RA), plays a crucial role in embryonic development (Zile, 1998). While it is essential, in excess it can also be harmful to any developing embryo (Zile, 1998). Isotretinoin, a derivative of vitamin A, is shown to have negative teratogenic effects to developing embryos (Wiens et al, 1992). While we know a lot about the negative side effects of isotretinoin, our understanding of how topical tretinoin cream will effect a developing embryos remains limited.

RA acts as a vital signaling molecule in embryogenesis, and its precise regulation is critical to proper embryonic development (Metzler et al, 2016) Excess RA can disrupt the developmental process due to interference in cellular differentiation and gene expression patterns (Motamedi et al, 2022) Studies have also shown that excess RA can lead to central nervous system, heart, and limb defects due to inappropriate activation of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) (Metzler et al, 2016). This inappropriate activations of RARs and RXRs can alter the expression of key developmental genes which can lead to abnormal cell proliferations, differentiation, and apoptosis (Motamendi et al, 2022). 

There is still limited research done on topical tretinoin's impact on embryonic development (Panchaud et al, 2012). While we have limited knowledge on how topical tretinoin will impact development, there are many studies on how excess RA/vitamin A will effect embryonic development. This includes disruptions to both hindbrain and spinal cord patterning (Ross et al, 2000). Excess RA or vitamin A has also been shown to cause a wide range of congenital malformations such as heart and limb defects on developing embryos ( Metzler et al, 2016).  Vitamin A deficency and excess can both cause malformations to developing embryos, which emphasizes the importance of vitamin A/RA for embryonic development (Zile, 1998). Given the known risks of excess vitamin A/RA exposure to developing embryos it is important to explore how topical tretinoin may impact embryonic development, as it is a vitamin A derivative commonly used in skincare around the world. 

We aimed to investigate how differing concentrations of tretinoin cream will affect embryonic development using a chick embryo as the model of study. In this study we examined the effects of three different concentrations of tretinoin cream: 0.025%, 0.05%, and 0.1%. We hypothesized that higher concentrations of the tretinoin cream will lead to lower heart rates, lower weights, and lower embryonic viability. 

The aim of this study is to examine the impact of topical tretinoin on chicken embryonic development. We predicted that topical tretinoin would decrease embryonic heart rate at higher concentrations. However, the results showed no statistical difference between the various concentrations and heart rates. Previous studies have shown that dysregulation of topic tretinoin causes heart malformations (Osmond et al., 1991). This is what led us to predict that it may also have an impact on embryonic heart rate. Although we did not see any significant impact on heart rate, the results showed a significant difference in viability between each treatment group. We found a positive relationship between cream concentration and viability rate for the embryos treated with tretinoin cream. We predicted that higher concentrations would have a more significant negative effect, which is not supported by this data, and the opposite is true. Previous studies have also shown that dysregulation of retinoic acid also leads to significant malformations (Saad, 2023). Our results showed a slightly significant difference in body weight, trending linearly with treatment concentration. The increasing viability and body weight of embryos treated with higher concentrations of tretinoin was unexpected. Retinoic acid plays a role in the transcription of genes related to development (Dreno, 2022). Although we predicted that higher concentrations would have adverse developmental effects, our data supports that the levels of tretinoin we are using may promote transcription of genes related to development at an appropriate level. However, the various treatment groups had no significant difference in length or head size. Because a great deal of previous research supports developmental abnormalities caused by dysregulation of retinoic acid, it is unexpected that topical tretinoin had no impact, even at higher concentrations. This warrants further study, including injecting the eggs with tretinoin to ensure the embryo absorbs a higher concentration. Finally, we noted that the CeraVe-treated eggs had the second-lowest overall development rate, which was unexpected. Further studies should be done on the potential impacts of CeraVe cream on embryonic development. 

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• Duong, T. B., & Waxman, J. S. (2021). Patterning of vertebrate cardiac progenitor fields by retinoic acid signaling. Genesis, 59(11), e23458. https://doi.org/10.1002/dvg.23458

• Metzler, M., & Sandell, L. (2016). Enzymatic metabolism of vitamin A in developing vertebrate embryos. Nutrients, 8(12), 812. https://doi.org/10.3390/nu8120812 

• Motamedi, M., Chehade, A., Sanghera, R., & Grewal, P. (2021). A clinician’s guide to topical retinoids. Journal of Cutaneous Medicine and Surgery, 26(1), 71–78. https://doi.org/10.1177/12034754211035091  

• Panchaud, A., Csajka, C., Merlob, P., Schaefer, C., Berlin, M., De Santis, M., Vial, T., Ieri, A., Malm, H., Eleftheriou, G., Stahl, B., Rousso, P., Winterfeld, U., Rothuizen, L. E., & Buclin, T. (2011). Pregnancy outcome following exposure to topical retinoids: a multicenter prospective study. The Journal of Clinical Pharmacology, 52(12), 1844–1851. https://doi.org/10.1177/0091270011429566 

• Pile, H. S., N. (2023). Isotretinoin. StatPearls.

• Ross, S. A., McCaffery, P. J., Drager, U. C., & De Luca, L. M. (2000). Retinoids in embryonal development. Physiological Reviews, 80(3), 1021–1054. https://doi.org/10.1152/physrev.2000.80.3.1021 

• Saad, K. A., E. (2023). The Effect of Retinoic Acid on Development of Chicken Embryos. AlQalam Journal of Medicine and Applied Sciences. 

• Vilches-Moure, J. G. (2019). Embryonic Chicken (Gallus gallus domesticus) as a Model of Cardiac Biology and Development. Comp Med, 69(3), 184-203. https://doi.org/10.30802/aalas-cm-18-000061

• Wiens, D. J., Mann, T. K., Fedderson, D. E., Rathmell, W. K., & Franck, B. H. (1992). Early heart development in the chick embryo: effects of isotretinoin on cell proliferation, α-actin synthesis, and development of contractions. Differentiation, 51(2), 105–112. https://doi.org/10.1111/j.1432-0436.1992.tb00686.x 

• Zile, M. H. (1998). Vitamin A and embryonic development: an overview. J Nutr, 128(2 Suppl), 455s-458s. https://doi.org/10.1093/jn/128.2.455S