Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic

Dietz, Runé; Gustavson, Kim; Sonne, Christian; Desforges, Jean‐Pierre; Rigét, Frank; Pavlová, Viola; McKinney, Melissa A.; Letcher, Robert J.

doi:10.1016/j.envres.2015.03.011

Cited by 80 publications

(62 citation statements)

References 88 publications

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“…Similar changes have occurred in East Greenland where harp seals and hooded seals (Cystophora cristata) have become more common and ringed seals (Pusa hispida) more scarce as polar bear prey (McKinney et al, 2013). Studies also have found associations between high levels of legacy chlorinated contaminants in certain polar bear subpopulations and biomarkers of toxic effects on endocrine, immune, and reproductive function (Bernhoft et al, 2000;Polischuk et al, 2002;Lie et al, 2004Lie et al, , 2005Letcher et al, 2010;Sonne, 2010;Bechshøft et al, 2012;Dietz et al, 2015;Jenssen et al, 2015).…”

Section: Introductionmentioning

confidence: 85%

Enhanced biological processes associated with alopecia in polar bears (Ursus maritimus)

Bowen

Miles

Stott

et al. 2015

Science of The Total Environment

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Populations of wildlife species worldwide experience incidents of mass morbidity and mortality. Primary or secondary drivers of these events may escape classical detection methods for identifying microbial insults, toxin exposure, or additional stressors. In 2012, 28% of polar bears sampled in a study in the southern Beaufort Sea region of Alaska had varying degrees of alopecia that was concomitant with reduced body condition. Concurrently, elevated numbers of sick or dead ringed seals were detected in the southern Beaufort, Chukchi, and Bering seas in 2012, resulting in the declaration of an unusual mortality event (UME) by the National Oceanic and Atmospheric Administration (NOAA). The primary and possible ancillary causative stressors of these events are unknown, and related physiological changes within individual animals have been undetectable using classical diagnostic methods. Here we present an emerging technology as a potentially guiding investigative approach aimed at elucidating the circumstances responsible for the susceptibility of certain polar bears to observed conditions. Using transcriptomic analysis we identified enhanced biological processes including immune response, viral defense, and response to stress in polar bears with alopecia. Our results support an alternative mechanism of investigation into the causative agents that, when used proactively, could serve as an early indicator for populations and species at risk. We suggest that current or classical methods for investigation into events of unusual morbidity and mortality can be costly, sometimes unfocused, and often inconclusive. Advances in technology allow for implementation of a holistic system of surveillance and investigation that could provide early warning of health concerns in wildlife species important to humans.

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Section: Introductionmentioning

confidence: 85%

Enhanced biological processes associated with alopecia in polar bears (Ursus maritimus)

Bowen

Miles

Stott

et al. 2015

Science of The Total Environment

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“…has been undertaken (Cropp et al, 2014;Hickie et al, 2013). In the Arctic, PBPK modelling of POPs in polar bears has been reported by Dietz et al (2015) and Sonne et al (2009), while a few other studies have dealt with PBPK modelling in humans though not focusing on distribution, bioaccumulation and excretion (Redding et al, 2008;Sonne et al, 2014a, b, c;Verner et al, 2009). The PBPK modelling in the present study estimated relatively low bioaccumulative levels of POPs in the sledge dogs and suggested that alveolar and faecal excretion are the most important routes of excretion.…”

Section: Considerationsmentioning

confidence: 98%

“…Previous studies have shown that PBPK modelling is a valuable tool to evaluate POP exposure and reproductive effects in polar bears by Dietz et al (2015) and Sonne et al (2009) which is the basis for the modelling of the present study. The present model is a further development of the previous two studies on polar bears and should be applied to e.g.…”

Section: Considerationsmentioning

confidence: 99%

Physiologically-based pharmacokinetic modelling of distribution, bioaccumulation and excretion of POPs in Greenland sledge dogs (Canis familiaris)

Sonne

Gustavson

Letcher

et al. 2015

Environmental Research

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“…Increasing evidence suggests that polar bear reproduction is affected by high POP burdens (Sonne 2010;Sonne et al 2009Sonne et al , 2012Dietz et al 2015;Gustavson et al 2015a), but available information on polar bear reproduction is limited.…”

Section: Introductionmentioning

confidence: 99%

Steroid hormones in multiple tissues of East Greenland polar bears (Ursus maritimus)

et al. 2016

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The polar bear (Ursus maritimus) is threatened by climate changes and also from persistent organic pollutants affecting polar bear endocrinology governing growth and reproduction. To provide further insight into basic polar bear endocrinology, we determined the levels of steroids in multiple tissues and plasma from East Greenland polar bears. Tissue samples from 10 polar bears, 5 males (2 adults, 3 juveniles) and 5 females (all juveniles) were obtained from the Inuit hunt in Scoresby Sound during springtime. Eleven steroids: pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, 17a-estradiol and 17b-estradiol were determined in brain, adrenal cortex, testis, testicular vein, plasma, and ovary using GC-MS/MS. In brain tissue, the neuroactive progestagen pregnenolone (11.9 ± 4.4 ng/g ww) and dehydroepiandrosterone (2.26 ± 0.43 ng/g ww) were found in high concentrations. Very high levels of testosterone and androstenedione were observed in testes ([100 ng/g ww) and plasma from testicular vein (testosterone: 108 ± 41 ng/ml; androstenedione: 35.2 ± 11.1 ng/ml). Additionally, a strong correlation was found between the levels of steroids in testes and testicular vein plasma. Progestagens were found in very high levels in ovaries from juvenile females ([100 ng/g ww). Finally, our study indicates that polar bears synthesize androstenedione via the D-4 pathway. The present study adds new insight to our knowledge on polar bear endocrinology, which may be used in future studies on polar bear ecology and studies on some of the threats from pollution and climate changes that these animals are facing.

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Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic

Cited by 80 publications

References 88 publications

Enhanced biological processes associated with alopecia in polar bears (Ursus maritimus)

Enhanced biological processes associated with alopecia in polar bears (Ursus maritimus)

Physiologically-based pharmacokinetic modelling of distribution, bioaccumulation and excretion of POPs in Greenland sledge dogs (Canis familiaris)

Steroid hormones in multiple tissues of East Greenland polar bears (Ursus maritimus)

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