{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:55:23Z","timestamp":1790801723286,"version":"4.1.0"},"reference-count":97,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 ES030374"],"award-info":[{"award-number":["R01 ES030374"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Over recent decades, an extensive array of anthropogenic chemicals have entered the environment and have been implicated in the increased incidence of an array of diseases, including metabolic syndrome. The ubiquitous presence of these environmental chemicals (ECs) necessitates the use of real\u2010life exposure models to the assess cumulative risk burden to metabolic health. Sheep that graze on biosolids\u2010treated pastures are exposed to a real\u2010life mixture of ECs such as phthalates, per\u2010 and polyfluoroalkyl substances, heavy metals, pharmaceuticals, pesticides, and metabolites thereof, and this EC exposure can result in metabolic disorders in their offspring. Using this model, we evaluated the effects of gestational exposure to a complex EC mixture on plasma triglyceride (TG) concentrations and metabolic and epigenetic regulatory genes in tissues key to energy regulation and storage, including the hypothalamus, liver, and adipose depots of 11\u2010month\u2010old male offspring. Our results demonstrated a binary effect of EC exposure on gene expression particularly in the hypothalamus. Principal component analysis revealed two subsets (B\u2010S1 [\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096] and B\u2010S2 [\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094]) within the biosolids group (B,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910), relative to the controls (C,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911). Changes in body weight, TG levels, and in gene expression in the hypothalamus, and visceral and subcutaneous fat were apparent between biosolid and control and the two subgroups of biosolids animals. These findings demonstrate that gestational exposure to an EC mixture results in differential regulation of metabolic processes in adult male offspring. Binary effects on hypothalamic gene expression and altered expression of lipid metabolism genes in visceral and subcutaneous fat, coupled with phenotypic outcomes, point to differences in individual susceptibility to EC exposure that could predispose vulnerable individuals to later metabolic dysfunction.\n                  <\/jats:p>","DOI":"10.1111\/jne.13358","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:09:22Z","timestamp":1702426162000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Preconceptional and in utero exposure of sheep to a real\u2010life environmental chemical mixture disrupts key markers of energy metabolism in male offspring"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2053-5566","authenticated-orcid":false,"given":"Mohammad","family":"Ghasemzadeh\u2010Hasankolaei","sequence":"first","affiliation":[{"name":"School of Biodiversity One Health and Veterinary Medicine College of Medical, Veterinary and Life Sciences, University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7869-0123","authenticated-orcid":false,"given":"Chris S.","family":"Elcombe","sequence":"additional","affiliation":[{"name":"School of Biodiversity One Health and Veterinary Medicine College of Medical, Veterinary and Life Sciences, University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Powls","sequence":"additional","affiliation":[{"name":"School of Biodiversity One Health and Veterinary Medicine College of Medical, Veterinary and Life Sciences, University 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