Introduction: A complex cocktail of poorly biodegradable chemicals is ubiquitous in the modern environment. Exposure to such chemicals contributes to diseases such as metabolic syndrome and infertility. Since the liver is the primary defence organ against xenotoxicants, we analysed the liver proteome of sheep continuously exposed (from pre-conception until early adulthood) to sewage sludge. Our aim was to identify dysregulated pathways and understand how a chemical cocktail can predispose for disease.
Materials and methods: Liver protein extracts from adult sheep that grazed on control or sewage sludge-fertilised pastures throughout their lives (gestation and lactation via the mother and post-weaning grazing) were divided in four groups (n=1012/group) according sex and treatment. Proteins were resolved using 2D differential in gel electrophoresis and compared using SameSpots Software. Differentially expressed protein spots were identified by tandem liquid chromatography/mass spectroscopy (LCMS/MS).
Results and discussion: Out of 445 gel spots, 229 were significantly different among the four groups. Sewage sludge exposure grossly affected the liver proteome by altering 193 spot volumes in male and/or female sheep compared to controls. 134 spots were differentially expressed by sex in controls, while exposure induced or abolished sex differences in 102 spots. We identified 20 proteins primarily involved in metabolic pathways relating to fatty acid metabolism (ACAA2, and ECHS1), steroid hormone synthesis/metabolism (APOA1, SCP2, and HSD17β10), and iron biology (TF, FLT, and HBA1/HBB). Our results show that life-long exposure to complex cocktails of everyday chemicals alters liver function, potentially laying the foundations for modern diseases.
Funding SRF Academic Scholarship Award 2013 to P A Fowler, OShaughnessy, P Filis.
02 - 04 Sep 2014
World Congress of Reproductive Biology