Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males

Filis, P. et al. (2019) Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males. Environment International, 124, pp. 98-108. (doi: 10.1016/j.envint.2019.01.003) (PMID:30641261)

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The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment (environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis. The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture. Four groups of sheep (n = 10-12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography/tandem mass spectroscopy. Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzo[a]anthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma-secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure. Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.

Item Type:Articles
Additional Information:This work was supported by the SRF Academic Scholarship Award 2013 (to PAF, PJOS, PF), the Wellcome Trust (080388 to PAF, CC, SMR, RMS, NPE) and the European Community's Seventh Framework Programme (FP7/2007-2013 to PAF, SMR, CC) under grant agreement no. 212885.
Glasgow Author(s) Enlighten ID:Bellingham, Dr Michelle and Evans, Professor Neil and O'Shaughnessy, Professor Peter
Authors: Filis, P., Walker, N., Robertson, L., Eaton-Turner, E., Ramona, L., Bellingham, M., Amezaga, M. R., Zhang, Z., Mandon-Pepin, B., Evans, N. P., Sharpe, R. M., Cotinot, C., Rees, W. D., O'Shaughnessy, P., and Fowler, P. A.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Environment International
ISSN (Online):0160-4120
Published Online:11 January 2019
Copyright Holders:Copyright © 2019 Elsevier
First Published:First published in Environment International 124:98-108
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
419423Effects of in-utero exposure to environmental chemicals via maternal pasture ingestion on fetal ovine reproductive developmentNeil EvansWellcome Trust (WELLCOTR)080388/Z/06/ZRI BIODIVERSITY ANIMAL HEALTH & COMPMED