ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Translational and Clinical Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1589826
This article is part of the Research TopicTransgenerational Effects of Endocrine Disrupting Chemicals: Unraveling Hormonal and Health Impacts Across GenerationsView all articles
Intergenerational metabolic toxicity of perfluorooctanesulfonic acid exposure in adult offspring rats: A multi-omics approach
Provisionally accepted
- 1Shanghai Jiao Tong University, Shanghai, China
- 2National University of Singapore, Singapore, Singapore
- 3Guilin Medical University, Guilin, Guangxi Zhuang Region, China
- 4International Peace Maternity and Child Health Hospital, Shanghai, Shanghai Municipality, China
- 5School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
- 6Duke University Medical Center, Duke University, Durham, North Carolina, United States
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Perfluorooctane sulfonate (PFOS), known as a critical endocrine disruptor, was linked to potential intergenerational effect in population studies. Yet, the toxic metabolic mechanisms remain unclear, particularly at relatively low PFOS concentration. This study investigated the metabolic impacts of early-life (pregnancy and lactation) PFOS exposure on adult Sprague-Dawley (SD) offspring rats using an integrated transcriptomics and metabolomics approach.Metabolic phenotypes, including glucose tolerance, lipids, and metabolic biomarkers were measured. Our results showed that early-life exposure to 0.03 mg/kg PFOS led to elevated fasting and 15-minute blood glucose, serum insulin, and adiponectin levels and a decrease of leptin level in dose of 0.3 mg/kg was observed. Differentially expressed genes induced by PFOS exposure were enriched in NOD-like receptor signaling, parathyroid hormone synthesis, secretion and action, unsaturated fatty acid biosynthesis, insulin signaling, retinol metabolism, fatty acid metabolism, glucagon signaling, type II diabetes, and PPAR signaling.Differentially expressed metabolites were linked to citric acid cycle, glycerophospholipid metabolism, and fatty acid biosynthesis. Co-enrichment analysis revealed feature changes in several pathways, including glycerophospholipid metabolism, sphingolipid metabolism, and primary bile acid synthesis (0.03 mg/kg), and retinol metabolism, linoleic acid metabolism, D-Glutamine and D-Glutamine biosynthesis, and fatty acid elongation (0.3 mg/kg). Taken together, early-life exposure to PFOS might lead to metabolic perturbations in adult offspring, which might be triggered by changes in pathways, i.g. glycerophospholipid metabolism, retinol metabolism, linoleic acid metabolism, and fatty acid elongation. Further validation of these pathways is required.
Keywords: Perfluorooctane sulfonate, Glucose homeostasis, early-life exposure, multi-omics, Intergenerational impact
Received: 08 Mar 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Yu, Tingyu Luo, Huo, Meng, Feng, Sun, Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Guoqi Yu, Shanghai Jiao Tong University, Shanghai, China
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