Toxicological mechanisms of emerging per-/poly-fluoroalkyl substances: Focusing on transcriptional activity and gene expression disruption

Lu Chen; Yue Xie; Minjie Li; Monika Mortimer; Fangfang Li; Liang-Hong Guo

doi:10.1016/j.tox.2023.153566

Toxicological mechanisms of emerging per-/poly-fluoroalkyl substances: Focusing on transcriptional activity and gene expression disruption

Toxicology. 2023 Aug 1:494:153566. doi: 10.1016/j.tox.2023.153566. Epub 2023 May 30.

Authors

Lu Chen¹, Yue Xie², Minjie Li³, Monika Mortimer⁴, Fangfang Li⁵, Liang-Hong Guo⁶

Affiliations

¹ College of Life Sciences, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China; Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China. Electronic address: s20090710005@cjlu.edu.cn.
² College of Life Sciences, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China; Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China. Electronic address: s20090710059@cjlu.edu.cn.
³ College of Quality and Safety Engineering, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China. Electronic address: mjli@cjlu.edu.cn.
⁴ Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China; College of Quality and Safety Engineering, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China. Electronic address: mmortimer@cjlu.edu.cn.
⁵ Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China; College of Quality and Safety Engineering, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China. Electronic address: liff@cjlu.edu.cn.
⁶ Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China; College of Quality and Safety Engineering, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China. Electronic address: lhguo@cjlu.edu.cn.

PMID: 37263573
DOI: 10.1016/j.tox.2023.153566

Abstract

Environmental and human monitoring studies have witnessed increasing occurrence of emerging per-/poly-fluoroalkyl substances (ePFASs) worldwide. Three classes of ePFASs, namely chlorinated polyfluoroalkylether sulfonic acids, hexafluoropropylene oxide homologues and short-chain perfluoroalkyl acids attracted the most attention. It is, therefore, the goal of this review to systematically and critically analyse the toxicity and toxicological mechanisms of these ePFASs based on the papers published between 2017 and 2022. The review summarized the main findings from both in vivo and in vitro studies, covering the hepatotoxicity of ePFASs and their interference with the endocrine system, including reproductive, developmental and thyroid toxicity. It also summarized the changes in gene expression in the hypothalamic-pituitary-thyroid axis and hypothalamic-pituitary-gonad axis of the model organisms after ePFASs exposure. The changes in gene expression in vitro and in vivo provide a clearer understanding of the toxicological mechanisms of ePFASs interference on hormonal levels (i.e., estradiol, testosterone, and thyroid hormones), developmental disturbance (e.g., swim bladder dysfunction) and lipid metabolism disruption (e.g., lipid droplet accumulation and hepatomegaly). In the end, future research directions on the toxicological mechanisms of ePFASs are suggested.

Keywords: Chlorinated polyfluoroalkylether sulfonic acid; Emerging per-/poly-fluoroalkyl substances; Hexafluoropropylene oxide; Short-chain perfluoroalkyl acids; Toxicological mechanisms.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Estradiol / metabolism
Fluorocarbons* / metabolism
Fluorocarbons* / toxicity
Gene Expression
Humans
Testosterone / metabolism
Thyroid Gland* / metabolism
Thyroid Hormones / metabolism

Substances

Thyroid Hormones
Testosterone
Estradiol
Fluorocarbons