ArticleThe Science of the total environment2023
Developmental programming: Preconceptional and gestational exposure of sheep to a real-life environmental chemical mixture alters maternal metabolome in a fetal sex-specific manner.
Article in The Science of the total environment, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Maternal exposure to biosolids reshapes chemical burden and steroidogenic pathways to promote adipogenic differentiation in a sheep model.Environment international · 2026Article
- Sex-specific multigenerational epigenetic responses to real-world chemical mixture exposure in an outbred sheep model.bioRxiv : the preprint server for biology · 2026Article
- Living in a chemical cocktail: real-world mixture exposures and their impact on ovarian function.The Journal of reproduction and development · 2026Review
- Interactions of the maternal microbiome with diet, stress, and infection influence fetal development.The FEBS journal · 2025Review
- Developmental programming: Sex-specific effects of prenatal exposure to a real-life mixture of environmental chemicals on liver function and transcriptome in sheep.Environmental pollution (Barking, Essex : 1987) · 2025Article
- Developmental programming: preconceptional and gestational exposure of sheep to biosolids on offspring ovarian dynamics†.Biology of reproduction · 2025Article
- IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Biosolids and male reproduction.Reproduction (Cambridge, England) · 2024Review
- Article
- Developmental programming: Impact of preconceptional and gestational exposure to a real-life environmental chemical mixture on maternal steroid, cytokine and oxidative stress milieus in sheep.The Science of the total environment · 2023Article
- Sexually dimorphic impact of preconceptional and gestational exposure to a real-life environmental chemical mixture (biosolids) on offspring growth dynamics and puberty in sheep.Environmental toxicology and pharmacology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundEveryday, 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.
objectiveTo determine if exposure to biosolids perturbs the maternal metabolic milieu of pregnant ewes, in a fetal sex-specific manner.
methodsEwes 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.
resultsUnivariate 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‑carbon metabolism. These factors are consistent with, and likely contribute to, the adverse phenotypic outcomes reported in the offspring.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.