Simple SummaryThis study examined how prenatal stress affects embryonic skin development. For this purpose, the model organism of the chicken embryo was used to inject the stress hormone corticosterone at an early embryonic stage. After a certain period of stress hormone exposure, macroscopic observations and tissue examinations were undertaken in order to pursue this research question. The investigations demonstrated that physiological skin development was significantly impaired by prenatal stress. This could be attributed to the fact that both cell-internal and -external components promoting cellular integrity were downregulated by the effects of stress hormones. In addition, it could be shown that the physiological cell proliferation was decreased due to prenatal stress exposure. Since artificially-produced stress hormones, so-called synthetic glucocorticoids, are also frequently used in everyday clinical practice, the authors suggest a constant reevaluation of glucocorticoid-associated treatment strategies on the basis of these results.AbstractPrenatal stress exposure is considered a risk factor for developmental deficits and postnatal behavioral disorders. While the effect of glucocorticoid-associated prenatal stress exposure has been comprehensively studied in many organ systems, there is a lack of in-depth embryological investigations regarding the effects of stress on the integumentary system. To approach this, we employed the avian embryo as a model organism and investigated the effects of systemic pathologically-elevated glucocorticoid exposure on the development of the integumentary system. After standardized corticosterone injections on embryonic day 6, we compared the stress-exposed embryos with a control cohort, using histological and immunohistochemical analyses as well as in situ hybridization. The overarching developmental deficits observed in the stress-exposed embryos were reflected through downregulation of both vimentin as well as fibronectin. In addition, a deficient composition in the different skin layers became apparent, which could be linked to a reduced expression of Dermo-1 along with significantly reduced proliferation rates. An impairment of skin appendage formation could be demonstrated by diminished expression of Sonic hedgehog. These results contribute to a more profound understanding of prenatal stress causing severe deficits in the integumentary system of developing organisms.