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‑carbon metabolism. These factors are consistent with, and likely contribute to, the adverse phenotypic outcomes reported in the offspring.
| Original language | English |
|---|---|
| Article number | 161054 |
| Journal | Science of the Total Environment |
| Volume | 864 |
| DOIs | |
| State | Published - Mar 15 2023 |
Bibliographical note
Publisher Copyright:© 2022 Elsevier B.V.
Funding
Funding support for the publication includes: National Institute of Environmental Health Sciences R01 ES030374 (PV, LR, ENP), Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) NIEHS Core Center P30 ES017885 (PV), Molecular Phenotyping Core, Michigan Nutrition and Obesity Center P30 DK089503. TSV is a Center Scientist in M-LEEaD NIEHS Core Center supported through P30 ES017885.Working with biosolids has several technical limitations compared to conventional chemical mixtures. It is difficult to give a toxicological assessment of biosolids as the composition is likely to vary from location to location and even between batches at the same location. However, this reflects real-life exposure in humans, as no one is exposed to the same set of chemicals at the same level. Although a study supported by the U.S. Environmental Protection Agency has recently documented a list of 726 chemicals present in biosolids (Richman et al., 2022), it is not practical to document the exact composition and concentrations of hundreds of chemicals that constitute the biosolids used in our study. Earlier publications have documented the chemical makeup of biosolids used at that time within this model. (Rhind et al., 2010; Rhind et al., 2005) The difference between the concentrations of biosolids in the soil, within the plant, or on the surface of the grass was not assessed in this study. However, it is likely that water soluble compounds will be taken up by the root of the grass and deposited within the grass blades, while lipophilic compounds will remain on the surface of the plant (Fries, 1995) and the grass (and some soil containing biosolids) are ingested by sheep. Apart from ingestion, other routes of exposure of sheep to biosolids includes inhalation and absorption (Evans et al., 2014). Additionally, sheep have ruminal microbes that could process some compounds found in biosolids into other forms, which could not be accounted for in this study. Although care was taken to ensure that the total nitrogen content was the same for both the biosolids-treated and the conventional fertilizer pastures, as nitrogen is usually the rate limiting nutrient for crop production (Blumenthal et al., 2008), the different types of fertilizer could impact the micro/macro nutrient content of the grass that may have contributed to differences in the metabolome. This, however, would be true when comparing any two types of fertilizer with different compositions.
| Funders | Funder number |
|---|---|
| Michigan Lifestage Environmental Exposures and Disease | |
| NIEHS Core Center | P30 ES017885 |
| National Institutes of Health/National Institute of Environmental Health Sciences | R01 ES030374 |
| U.S. Environmental Protection Agency | |
| Michigan Nutrition Obesity Research Center, Medical School, University of Michigan | P30 DK089503 |
Keywords
- Biosolids
- Environmental chemical mixture
- Prenatal exposure
- Sex-specific
- Untargeted metabolomics
ASJC Scopus subject areas
- Environmental Engineering
- Environmental Chemistry
- Waste Management and Disposal
- Pollution
