Multi-omics reveal disturbance of glucose homeostasis in pregnant rats exposed to short-chain perfluorobutanesulfonic acid

Yu，Guoqi1,2,3; Luo，Tingyu4; Liu，Yongjie1; Huo，Xiaona5; Mo，Chunbao6; Huang，Bo4; Li，You4; Feng，Liping7; Sun，Yan4; Zhang，Jun1; Zhang，Zhiyong4,8

2024-06-15

10.1016/j.ecoenv.2024.116402

Ecotoxicology and Environmental Safety   影响因子和分区

0147-6513

1090-2414

Perfluorobutanesulfonic acid (PFBS), a short-chain alternative to perfluorooctanesulfonic acid (PFOS), is widely used in various products and is increasingly present in environmental media and human bodies. Recent epidemiological findings have raised concerns about its potential adverse health effects, although the specific toxic mechanism remains unclear. This study aimed to investigate the metabolic toxicity of gestational PFBS exposure in maternal rats. Pregnant Sprague Dawley (SD) rats were randomly assigned to three groups and administered either 3 % starch gel (control), 5, or 50 mg/kg bw·d PFBS. Oral glucose tolerance tests (OGTT) and lipid profiles were measured, and integrated omics analysis (transcriptomics and non-targeted metabolomics) was employed to identify changes in genes and metabolites and their relationships with metabolic phenotypes. The results revealed that rats exposed to 50 mg/kg bw·d PFBS exhibited a significant decrease in 1-h glucose levels and the area under the curve (AUC) of OGTT compared with the starch group. Transcriptomics analysis indicated significant alterations in gene expression related to cytochrome P450 exogenous metabolism, glutathione metabolism, bile acid secretion, tumor pathways, and retinol metabolism. Differentially expressed metabolites (DEMs) were enriched in pathways such as pyruvate metabolism, the glucagon signaling pathway, central carbon metabolism in cancer, and the citric acid cycle. Co-enrichment analysis and pairwise correlation analysis among genes, metabolites, and outcomes identified several differentially expressed genes (DEGs), including Gstm1, Kit, Adcy1, Gck, Ppp1r3c, Ppp1r3d, and DEMs such as fumaric acid, L-lactic acid, 4-hydroxynonenal, and acetylvalerenolic acid. These DEGs and DEMs may play a role in the modulation of glucolipid metabolic pathways. In conclusion, our results suggest that gestational exposure to PFBS may induce molecular perturbations in glucose homeostasis. These findings provide insights into the potential mechanisms contributing to the heightened risk of abnormal glucose tolerance associated with PFBS exposure.

Glucose perturbation Omics Perfluorobutanesulfonic acid Pregnancy

SCI

英语

其他

ENVIRONMENT/ECOLOGY

2-s2.0-85192293954

Scopus

1.Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200092,China
2.Global Centre for Asian Women's Health,Yong Loo Lin School of Medicine,National University of Singapore,117549,Singapore
3.Department of Obstetrics & Gynaecology,Yong Loo Lin School of Medicine,National University of Singapore,117549,Singapore
4.School of Public Health,Guilin Medical University,Guilin,541001,China
5.International Peace Maternity and Child Health Hospital,Shanghai,200030,China
6.School of Public Health and Emergency Management,Southern University of Science and Technology,Shenzhen,518055,China
7.Department of Obstetrics and Gynecology,Duke University Medical Center,Durham,United States
8.The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath,Guilin Medical University,Guilin,541001,China

Yu，Guoqi,Luo，Tingyu,Liu，Yongjie,et al. Multi-omics reveal disturbance of glucose homeostasis in pregnant rats exposed to short-chain perfluorobutanesulfonic acid[J]. Ecotoxicology and Environmental Safety,2024,278.

Yu，Guoqi.,Luo，Tingyu.,Liu，Yongjie.,Huo，Xiaona.,Mo，Chunbao.,...&Zhang，Zhiyong.(2024).Multi-omics reveal disturbance of glucose homeostasis in pregnant rats exposed to short-chain perfluorobutanesulfonic acid.Ecotoxicology and Environmental Safety,278.

Yu，Guoqi,et al."Multi-omics reveal disturbance of glucose homeostasis in pregnant rats exposed to short-chain perfluorobutanesulfonic acid".Ecotoxicology and Environmental Safety 278(2024).