Adipose tissue transcriptome is related to pollutant exposure in polar bear mother-cub pairs from Svalbard, Norway.

Being at the food chain apex, polar bears (Ursus maritimus) are highly contaminated with persistent organic pollutants (POPs). Females transfer POPs to their offspring through gestation and lactation, therefore, young cubs present higher POPs concentrations than their mothers. Recent studies suggest that POPs affect lipid metabolism in female polar bears, however, the mechanisms and impact on their offspring remain unknown. Here, we hypothesized that exposure to POPs differentially alters genome-wide gene transcription in adipose tissue from mother polar bears and their cubs, highlighting molecular differences in response between adults and young. Adipose tissue biopsies were collected from 13 adult female polar bears and their twin cubs in Svalbard, Norway, in April 2011, 2012 and 2013. Total RNA extracted from biopsies was subjected to next-generation RNA sequencing. Plasma concentrations of summed PCBs, organochlorine pesticides and polybrominated diphenyl ethers in mothers ranged from 897 to 13,620 ng/g wet weight and were associated with altered adipose tissue gene expression in both mothers and cubs. In mothers, 2,502 and 2,586 genes in total were respectively positively and negatively correlated to POP exposure, whereas in cubs, 2,585 positively and 1,690 negatively genes. Between mothers and cubs, 743 positively and negatively genes overlapped between mothers and cubs suggesting partially shared molecular responses to ΣPOPs. ΣPOPs associated genes were involved in numerous metabolic pathways in mothers and cubs, indicating that POP exposure alters energy metabolism, which, in turn, may be linked to metabolic dysfunction.

[1]  M. Dalvai,et al.  Prenatal Exposure to Environmentally-Relevant Contaminants Perturbs Male Reproductive Parameters Across Multiple Generations that are Partially Protected by Folic Acid Supplementation , 2019, Scientific Reports.

[2]  A. Marette,et al.  Maternal folic acid supplementation does not counteract the deleterious impact of prenatal exposure to environmental pollutants on lipid homeostasis in male rat descendants , 2019, Journal of Developmental Origins of Health and Disease.

[3]  R. Dietz,et al.  State of knowledge on current exposure, fate and potential health effects of contaminants in polar bears from the circumpolar Arctic. , 2019, The Science of the total environment.

[4]  R. Dietz,et al.  Temporal trends of persistent organic pollutants in Arctic marine and freshwater biota. , 2019, The Science of the total environment.

[5]  F. Giorgino,et al.  Insulin and Insulin Receptors in Adipose Tissue Development , 2019, International journal of molecular sciences.

[6]  J. Olivier,et al.  Epigenetic and Neurological Impairments Associated with Early Life Exposure to Persistent Organic Pollutants , 2019, International journal of genomics.

[7]  M. Dyck,et al.  Concentrations of legacy and new contaminants are related to metabolite profiles in Hudson Bay polar bears , 2019, Environmental research.

[8]  J. Welker,et al.  Temporal Trends of Persistent Organic Pollutants in Barents Sea Polar Bears ( Ursus maritimus) in Relation to Changes in Feeding Habits and Body Condition. , 2018, Environmental science & technology.

[9]  A. Kong,et al.  Early-life exposure to endocrine disrupting chemicals associates with childhood obesity , 2018, Annals of pediatric endocrinology & metabolism.

[10]  D. Lee,et al.  Persistent Organic Pollutants and Type 2 Diabetes: A Critical Review of Review Articles , 2018, Front. Endocrinol..

[11]  Guihua Liu,et al.  The PI3K/AKT pathway in obesity and type 2 diabetes , 2018, International journal of biological sciences.

[12]  R. Dietz,et al.  Immunologic, reproductive, and carcinogenic risk assessment from POP exposure in East Greenland polar bears (Ursus maritimus) during 1983-2013. , 2018, Environment international.

[13]  J. Aars,et al.  Multiple-stressor effects in an apex predator: combined influence of pollutants and sea ice decline on lipid metabolism in polar bears , 2017, Scientific Reports.

[14]  J. Aars,et al.  Potentiation of ecological factors on the disruption of thyroid hormones by organo‐halogenated contaminants in female polar bears (Ursus maritimus) from the Barents Sea , 2017, Environmental research.

[15]  Chae-Myeong Ha,et al.  Low-Dose Persistent Organic Pollutants Impair Insulin Secretory Function of Pancreatic β-Cells: Human and In Vitro Evidence , 2017, Diabetes.

[16]  I. Birol,et al.  De novo assembly of the ringed seal (Pusa hispida) blubber transcriptome: A tool that enables identification of molecular health indicators associated with PCB exposure. , 2017, Aquatic toxicology.

[17]  Laura N. Vandenberg,et al.  Metabolism disrupting chemicals and metabolic disorders. , 2017, Reproductive toxicology.

[18]  J. Welker,et al.  Sea ice-associated decline in body condition leads to increased concentrations of lipophilic pollutants in polar bears (Ursus maritimus) from Svalbard, Norway. , 2017, The Science of the total environment.

[19]  I. Sylte,et al.  Environmental Chemicals Modulate Polar Bear (Ursus maritimus) Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and Adipogenesis in Vitro. , 2016, Environmental science & technology.

[20]  Liegang Liu,et al.  Pesticide exposure and risk of Alzheimer’s disease: a systematic review and meta-analysis , 2016, Scientific Reports.

[21]  M. Soler‐Lopez,et al.  Dynamics of Human Mitochondrial Complex I Assembly: Implications for Neurodegenerative Diseases , 2016, Front. Mol. Biosci..

[22]  J. Hirst,et al.  Structure of mammalian respiratory complex I , 2016, Nature.

[23]  L. Pachter,et al.  Erratum: Near-optimal probabilistic RNA-seq quantification , 2016, Nature Biotechnology.

[24]  Måns Magnusson,et al.  MultiQC: summarize analysis results for multiple tools and samples in a single report , 2016, Bioinform..

[25]  E. Ha,et al.  Serum Levels of Persistent Organic Pollutants and Insulin Secretion among Children Age 7–9 Years: A Prospective Cohort Study , 2016, Environmental health perspectives.

[26]  Palaniyandi Ravanan,et al.  Secret talk between adipose tissue and central nervous system via secreted factors—an emerging frontier in the neurodegenerative research , 2016, Journal of Neuroinflammation.

[27]  A C Gore,et al.  EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals. , 2015, Endocrine reviews.

[28]  T. K. Jensen,et al.  Prenatal exposure to persistent organochlorine pollutants is associated with high insulin levels in 5-year-old girls. , 2015, Environmental research.

[29]  R. Dietz,et al.  Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus). , 2015, Environmental research.

[30]  H. Chan,et al.  Assessment of neurotoxic effects of mercury in beluga whales (Delphinapterus leucas), ringed seals (Pusa hispida), and polar bears (Ursus maritimus) from the Canadian Arctic. , 2015, The Science of the total environment.

[31]  H. Chan,et al.  In vivo and in vitro changes in neurochemical parameters related to mercury concentrations from specific brain regions of polar bears (Ursus maritimus) , 2014, Environmental toxicology and chemistry.

[32]  C. Wesseling,et al.  Organochlorine chemicals and neurodegeneration among elderly subjects in Costa Rica. , 2014, Environmental research.

[33]  M. Benoit-Biancamano,et al.  Characterization of a pancreatic islet cell tumor in a polar bear (Ursus maritimus). , 2014, Zoo biology.

[34]  T. K. Jensen,et al.  Polychlorinated biphenyl exposure and glucose metabolism in 9-year-old Danish children. , 2014, The Journal of clinical endocrinology and metabolism.

[35]  G. Brent,et al.  Thyroid hormone regulation of metabolism. , 2014, Physiological reviews.

[36]  Björn Usadel,et al.  Trimmomatic: a flexible trimmer for Illumina sequence data , 2014, Bioinform..

[37]  M. Vrijheid,et al.  Prenatal exposure to persistent organic pollutants and rapid weight gain and overweight in infancy , 2014, Obesity.

[38]  Laura N. Vandenberg,et al.  Chlorinated persistent organic pollutants, obesity, and type 2 diabetes. , 2014, Endocrine reviews.

[39]  J. R. Craer,et al.  "Developmental Effects of Endocrine-Disrupting Chemicals in Wildlife and Humans" (1993), by Theo Colborn, Frederick S. vom Saal, and Ana M. Soto , 2014 .

[40]  K. Thayer,et al.  Environmental Chemicals and Type 2 Diabetes: An Updated Systematic Review of the Epidemiologic Evidence , 2013, Current Diabetes Reports.

[41]  Kyla W. Taylor,et al.  Evaluation of the Association between Persistent Organic Pollutants (POPs) and Diabetes in Epidemiological Studies: A National Toxicology Program Workshop Review , 2013, Environmental health perspectives.

[42]  M. Lamoree,et al.  Transthyretin-binding activity of contaminants in blood from polar bear (Ursus maritimus) cubs. , 2013, Environmental science & technology.

[43]  Teresa Oliveira,et al.  Biochemistry of adipose tissue: an endocrine organ , 2013, Archives of medical science : AMS.

[44]  J. Barrett POPs vs. Fat: Persistent Organic Pollutant Toxicity Targets and Is Modulated by Adipose Tissue , 2013, Environmental health perspectives.

[45]  I. Stirling,et al.  Effects of climate warming on polar bears: a review of the evidence , 2012, Global change biology.

[46]  J. Aars,et al.  PCBs and OH-PCBs in polar bear mother-cub pairs: a comparative study based on plasma levels in 1998 and 2008. , 2012, The Science of the total environment.

[47]  D. Boyd,et al.  Blood-based biomarkers of selenium and thyroid status indicate possible adverse biological effects of mercury and polychlorinated biphenyls in Southern Beaufort Sea polar bears. , 2011, Environmental research.

[48]  L. Madsen,et al.  Chronic Consumption of Farmed Salmon Containing Persistent Organic Pollutants Causes Insulin Resistance and Obesity in Mice , 2011, PloS one.

[49]  R. Dietz,et al.  Flame retardants and legacy contaminants in polar bears from Alaska, Canada, East Greenland and Svalbard, 2005-2008. , 2011, Environment international.

[50]  M. Kogevinas,et al.  Prenatal Organochlorine Compound Exposure, Rapid Weight Gain, and Overweight in Infancy , 2010, Environmental health perspectives.

[51]  R. Dietz,et al.  Exposure and effects assessment of persistent organohalogen contaminants in arctic wildlife and fish. , 2010, The Science of the total environment.

[52]  K. Kristiansen,et al.  Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome , 2009, Environmental health perspectives.

[53]  Yidong Bai,et al.  Mitochondrial respiratory complex I: structure, function and implication in human diseases. , 2009, Current medicinal chemistry.

[54]  I. Stirling,et al.  POLAR BEAR DIETS AND ARCTIC MARINE FOOD WEBS: INSIGHTS FROM FATTY ACID ANALYSIS , 2008 .

[55]  R. Dietz,et al.  Target tissue selectivity and burdens of diverse classes of brominated and chlorinated contaminants in polar bears (Ursus maritimus) from East Greenland. , 2008, Environmental science & technology.

[56]  D. Corella,et al.  Metabolic syndrome pathophysiology: the role of adipose tissue. , 2007, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[57]  Bruce M. Spiegelman,et al.  Adipocytes as regulators of energy balance and glucose homeostasis , 2006, Nature.

[58]  R. Dietz,et al.  Xenoendocrine pollutants may reduce size of sexual organs in East Greenland polar bears (Ursus maritimus). , 2006, Environmental science & technology.

[59]  R. Dietz,et al.  Brominated flame retardants in polar bears (Ursus maritimus) from Alaska, the Canadian Arctic, East Greenland, and Svalbard. , 2006, Environmental science & technology.

[60]  R. Dietz,et al.  Chlorinated hydrocarbon contaminants and metabolites in polar bears (Ursus maritimus) from Alaska, Canada, East Greenland, and Svalbard: 1996-2002. , 2005, The Science of the total environment.

[61]  Ø. Wiig,et al.  Relationships between PCBs and thyroid hormones and retinol in female and male polar bears. , 2004, Environmental health perspectives.

[62]  R. Stahlmann,et al.  Developmental toxicity of polychlorinated biphenyls (PCBs): a systematic review of experimental data , 2004, Archives of Toxicology.

[63]  Ø. Wiig,et al.  Diet composition of polar bears in Svalbard and the western Barents Sea , 2002, Polar Biology.

[64]  Ø. Wiig,et al.  Geographic variation of PCB congeners in polar bears (Ursus maritimus) from Svalbard east to the Chukchi Sea , 2001, Polar Biology.

[65]  P. Eriksson,et al.  Developmental neurotoxicity of four ortho-substituted polychlorinated biphenyls in the neonatal mouse. , 1996, Environmental toxicology and pharmacology.

[66]  M. Ramsay,et al.  Changes in the Body Composition of Fasting Polar Bears (Ursus maritimus): The Effect of Relative Fatness on Protein Conservation , 1996, Physiological Zoology.

[67]  M. Hadders‐Algra,et al.  Perinatal exposure to polychlorinated biphenyls and dioxins and its effect on neonatal neurological development. , 1995, Early human development.

[68]  R. Letcher,et al.  Preliminary results of fasting on the kinetics of organochlorines in polar bears (Ursus maritimus). , 1995, The Science of the total environment.

[69]  U. K. Misra,et al.  Changes in lipid profiles of liver microsomes of rats following intratracheal administration of DDT or endosulfan. , 1990, Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes.

[70]  E. Levin,et al.  Effects of perinatal PCB exposure on discrimination-reversal learning in monkeys. , 1989, Neurotoxicology and teratology.

[71]  G. Pantaleoni,et al.  Effects of Maternal Exposure to Polychlorobiphenyls (PCBs) on F1 Generation Behavior in the Rat , 1988 .

[72]  I. Stirling,et al.  Reproductive biology and ecology of female polar bears (Ursus maritimus) , 1988 .

[73]  B. N. Gupta,et al.  Biochemical effects of pure isomers of hexachlorobiphenyl: fatty livers and cell structure. , 1979, Chemico-biological interactions.

[74]  S. Tartu,et al.  Ecotoxicologic Stress in Arctic Marine Mammals, With Particular Focus on Polar Bears , 2018 .

[75]  B. Gao,et al.  Alcohol, adipose tissue and liver disease: mechanistic links and clinical considerations , 2018, Nature Reviews Gastroenterology & Hepatology.

[76]  E. Peacock,et al.  Temporal complexity of southern Beaufort Sea polar bear diets during a period of increasing land use , 2017 .

[77]  A. Goksøyr,et al.  MRNA expression of genes regulating lipid metabolism in ringed seals (Pusa hispida) from differently polluted areas. , 2014, Aquatic toxicology.

[78]  T. K. Jensen,et al.  Association between prenatal polychlorinated biphenyl exposure and obesity development at ages 5 and 7 y: a prospective cohort study of 656 children from the Faroe Islands. , 2014, The American journal of clinical nutrition.

[79]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[80]  Ø. Wiig,et al.  Organochlorines in polar bears (Ursus maritimus) at Svalbard. , 1997, Environmental pollution.

[81]  A. A. Spector,et al.  Characterization of the plasma lipids and lipoproteins of the polar bear , 1981 .

[82]  J. Lentfer,et al.  Modes of thermal protection in polar bear cubs--at birth and on emergence from the den. , 1979, The American journal of physiology.