title: Contaminant-associated disruption of vitamin A and its receptor (retinoic acid receptor alpha) in free-ranging harbour seals (Phoca vitulina).
abstract: Polychlorinated biphenyls (PCBs) have been associated with a number of toxic effects in marine mammals such as endocrine disruption and immunotoxicity that, in turn, are widely thought to have contributed to population level impacts including reproductive failure and outbreaks of disease. In this study, the dietary hormone vitamin A and expression levels of one of its receptors, retinoic acid receptor alpha (RARalpha), were used as biomarkers of PCB-associated health effects in harbour seals. Harbour seal pups (n=24) were live-captured in coastal British Columbia, Canada, and Washington State, USA, and sampled for whole blood (to obtain peripheral blood mononuclear cells, PBMCs) and blood plasma, as well as biopsies of blubber and skin. Concentrations of circulatory vitamin A (retinol) in plasma and stored vitamin A in blubber were negatively associated with blubber PCB concentrations (R=-0.518, p=0.013 and R=-0.645, p=0.009, respectively). However, vitamin A concentrations in skin, an important target tissue, remained constant, which likely reflects a compensatory transfer from blubber to maintain physiological functions. In addition, we characterized the harbour seal RARalpha, and investigated its expression levels as a potential biomarker in seals. RARalpha expression in blubber, but not on PBMCs, was elevated in more contaminated animals (R=0.580, p=0.009). This may represent a direct contaminant-related effect, or, a compensation for the contaminant-related disruption of (circulatory and/or blubber) hormone levels. Since vitamin A is critical to developmental, reproductive and immunological health, our observations of a contaminant-related disruption of its physiology in free-ranging seals may portend population level consequences. Vitamin A concentrations and RARalpha expression levels can therefore represent relevant and sensitive biomarkers of PCB-associated toxic effects in toxicological studies of marine mammals.
authors.affiliation: Institute of Ocean Sciences, Fisheries and Oceans Canada, 9860 West Saanich Road, Sidney, BC, Canada V8L 4B2.
authors.forename: L
authors.initials: L
authors.lastname: Mos
authors.forename: M
authors.initials: M
authors.lastname: Tabuchi
authors.forename: N
authors.initials: N
authors.lastname: Dangerfield
authors.forename: S J
authors.initials: SJ
authors.lastname: Jeffries
authors.forename: B F
authors.initials: BF
authors.lastname: Koop
authors.forename: P S
authors.initials: PS
authors.lastname: Ross
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000662:veterinary; D008297:Male; D008969:Molecular Sequence Data; D046049:Phoca / Q000502:physiology*; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000633:toxicity*; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000737:chemistry; D013223:Statistics as Topic; D014801:Vitamin A / Q000032:analysis*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014874:Water Pollutants, Chemical; D014801:Vitamin A; D011078:Polychlorinated Biphenyls