Characterization and environmental stressor effects on the vitamin D pathway in skin of the Atlantic bottlenose dolphin (Tursiops truncatus)

The evident impact that the environment has taken on the health of the Atlantic bottlenose dolphin necessitates greater knowledge of this marine mammal's response to external stressors. In order to better elucidate the mechanisms linking environmental health with dolphin health, cell cultures have been established from dolphin skin as in vitro tools for molecular evaluations. These cell models have been used to investigate the role of the vitamin D pathway within dolphin skin. Vitamin D3 is of interest because of its acknowledged chemopreventative and immunomodulatory properties, which are considered its more recently-discovered, nonclassical functions. Within the skin, UVB radiation stimulates the conversion of 7-dehydrocholesterol into the active, hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25D3). 1,25D3 exerts a biological function via interaction with the nuclear vitamin D receptor (VDR), a potent regulator of gene transcription. Whether marine mammals express this pathway and gain the same immune benefits from vitamin D3 as terrestrial animals is unknown. This work provides evidence that dolphin skin cells respond at the molecular level to exogenous 1,25D3 administration via upregulation of VDR and alterations in transcriptomic profiles. Cellular responses to the hormone include an induction of apoptosis and a decrease in proliferative capabilities. All of these are similar effects to those reported in terrestrial animals and are consistent with the nonclassical roles of vitamin D. The research question addressed is whether environmental stressors interfere with vitamin D responses in dolphin skin, proposing a possible mechanism for the detrimental impact of environmental fluctuations on marine mammal health. Nonlethal exposures of methylmercury and thermal stress, two stressors of relevance in the dolphin's environment, each modulated 1,25D3-inducible VDR levels and transcriptional responses in dolphin skin cells. The findings presented here shed light towards, one, the function of the vitamin D pathway in a novel species model and, two, the impacts of environmental stress on 1,25D3 signaling. Considering the similarities detected for this pathway between humans and dolphins, the results of this study may extend to other species.