| Title: | Developmental programming: Preconceptional and gestational exposure of sheep to a real-life environmental chemical mixture alters maternal metabolome in a fetal sex-specific manner |
| Author(s): | Thangaraj SV; Kachman M; Halloran KM; Sinclair KD; Lea R; Bellingham M; Evans NP; Padmanabhan V; |
| Address: | "Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA. MM BRCF Metabolomics Core, University of Michigan, Ann Arbor, MI, USA. University of Nottingham, Sutton Bonington Campus, Loughborough, UK. School of Biodiversity One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK. Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA. Electronic address: vasantha@umich.edu" |
| DOI: | 10.1016/j.scitotenv.2022.161054 |
| ISSN/ISBN: | 1879-1026 (Electronic) 0048-9697 (Print) 0048-9697 (Linking) |
| Abstract: | "BACKGROUND: Everyday, humans are exposed to a mixture of environmental chemicals some of which have endocrine and/or metabolism disrupting actions which may contribute to non-communicable diseases. The adverse health impacts of real-world chemical exposure, characterized by chronic low doses of a mixture of chemicals, are only recently emerging. Biosolids derived from human waste represent the environmental chemical mixtures humans are exposed to in real life. Prior studies in sheep have shown aberrant reproductive and metabolic phenotypes in offspring after maternal biosolids exposure. OBJECTIVE: To determine if exposure to biosolids perturbs the maternal metabolic milieu of pregnant ewes, in a fetal sex-specific manner. METHODS: Ewes were grazed on inorganic fertilizer (Control) or biosolids-treated pastures (BTP) from before mating and throughout gestation. Plasma from pregnant ewes (Control n = 15, BTP n = 15) obtained mid-gestation were analyzed by untargeted metabolomics. Metabolites were identified using Agilent MassHunter. Multivariate analyses were done using MetaboAnalyst 5.0 and confirmed using SIMCA. RESULTS: Univariate and multivariate analysis of 2301 annotated metabolites identified 193 differentially abundant metabolites (DM) between control and BTP sheep. The DM primarily belonged to the super-class of lipids and organic acids. 15-HeTrE, oleamide, methionine, CAR(3:0(OH)) and pyroglutamic acid were the top DM and have been implicated in the regulation of fetal growth and development. Fetal sex further exacerbated differences in metabolite profiles in the BTP group. The organic acids class of metabolites was abundant in animals with male fetuses. Prenol lipid, sphingolipid, glycerolipid, alkaloid, polyketide and benzenoid classes showed fetal sex-specific responses to biosolids. DISCUSSION: Our study illustrates that exposure to biosolids significantly alters the maternal metabolome in a fetal sex-specific manner. The altered metabolite profile indicates perturbations to fatty acid, arginine, branched chain amino acid and one?ª╡carbon metabolism. These factors are consistent with, and likely contribute to, the adverse phenotypic outcomes reported in the offspring" |
| Keywords: | Pregnancy Sheep Animals Female Male Humans Biosolids *Fetal Development *Maternal Exposure Metabolome Sex Characteristics Environmental chemical mixture Prenatal exposure Sex-specific Untargeted metabolomics; |
| Notes: | "MedlineThangaraj, S V Kachman, M Halloran, K M Sinclair, K D Lea, R Bellingham, M Evans, N P Padmanabhan, V eng P30 DK089503/DK/NIDDK NIH HHS/ P30 ES017885/ES/NIEHS NIH HHS/ R01 ES030374/ES/NIEHS NIH HHS/ Netherlands 2022/12/25 Sci Total Environ. 2023 Mar 15; 864:161054. doi: 10.1016/j.scitotenv.2022.161054. Epub 2022 Dec 21" |
