Preconceptional and in-utero exposure of sheep to a real-life environmental chemical mixture disrupts key markers of energy metabolism in male offspring

Ghasemzadeh Hasankolaei, M., Elcombe, C. S., Lea, R. G., Powls, S., Sinclair, K. D., Padmanabhan, V., Evans, N. P. and Bellingham, M. (2024) Preconceptional and in-utero exposure of sheep to a real-life environmental chemical mixture disrupts key markers of energy metabolism in male offspring. Journal of Neuroendocrinology, 36(1), e13358. (doi: 10.1111/jne.13358) (PMID:38087451)

Abstract

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-life exposure models to the assess cumulative risk burden to metabolic health. Sheep that graze on biosolids-treated pastures are exposed to a real-life mixture of ECs such as phthalates, per- 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-month-old 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-S1 [n = 6] and B-S2 [n = 4]) within the biosolids group (B, n = 10), relative to the controls (C, n = 11). 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.

• Item Type: Articles
• Additional Information: This study was supported by a grant from the National Institutes of Health, USA (R01 ES030374).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bellingham, Dr Michelle and Evans, Professor Neil and Ghasemzadeh Hasankolaei, Maryam

Creator Roles

Ghasemzadeh Hasankolaei, M.: Investigation, Methodology, Writing – original draft, Data curation, Formal analysis
Evans, N.: Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review and editing, Funding acquisition, Supervision, Project administration
Bellingham, M.: Conceptualization, Methodology, Writing – original draft, Writing – review and editing, Funding acquisition, Supervision, Project administration

• Authors: Ghasemzadeh Hasankolaei, M., Elcombe, C. S., Lea, R. G., Powls, S., Sinclair, K. D., Padmanabhan, V., Evans, N. P., and Bellingham, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine; College of Science and Engineering
• Journal Name: Journal of Neuroendocrinology
• Publisher: Wiley
• ISSN: 0953-8194
• ISSN (Online): 1365-2826
• Published Online: 12 December 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Journal of Neuroendocrinology 36(1):e13358
• Publisher Policy: Reproduced under a Creative Commons license