Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis
Emerging epidemiological evidence has linked per- and polyfluoroalkyl substances (PFAS) exposure could be linked to the disturbance of gestational glucolipid metabolism, but the toxicological mechanism is unclear, especially when the exposure is at a low level. This study examined the glucolipid met...
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Elsevier
2023-03-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412023001241 |
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| author | Guoqi Yu Jinguo Wang Yongjie Liu Tingyu Luo Xi Meng Ruiyuan Zhang Bo Huang Yan Sun Jun Zhang |
| author_facet | Guoqi Yu Jinguo Wang Yongjie Liu Tingyu Luo Xi Meng Ruiyuan Zhang Bo Huang Yan Sun Jun Zhang |
| author_sort | Guoqi Yu |
| collection | DOAJ |
| description | Emerging epidemiological evidence has linked per- and polyfluoroalkyl substances (PFAS) exposure could be linked to the disturbance of gestational glucolipid metabolism, but the toxicological mechanism is unclear, especially when the exposure is at a low level. This study examined the glucolipid metabolic changes in pregnant rats treated with relatively low dose perfluorooctanesulfonic acid (PFOS) through oral gavage during pregnancy [gestational day (GD): 1–18]. We explored the molecular mechanisms underlying the metabolic perturbation. Oral glucose tolerance test (OGTT) and biochemical tests were performed to assess the glucose homeostasis and serum lipid profiles in pregnant Sprague-Dawley (SD) rats randomly assigned to starch, 0.03 and 0.3 mg/kg·bw·d groups. Transcriptome sequencing combined with non-targeted metabolomic assays were further performed to identify differentially altered genes and metabolites in the liver of maternal rats, and to determine their correlation with the maternal metabolic phenotypes. Results of transcriptome showed that differentially expressed genes at 0.03 and 0.3 mg/kg·bw·d PFOS exposure were related to several metabolic pathways, such as peroxisome proliferator-activated receptors (PPARs) signaling, ovarian steroid synthesis, arachidonic acid metabolism, insulin resistance, cholesterol metabolism, unsaturated fatty acid synthesis, bile acid secretion. The untargeted metabolomics identified 164 and 158 differential metabolites in 0.03 and 0.3 mg/kg·bw·d exposure groups, respectively under negative ion mode of Electrospray Ionization (ESI-), which could be enriched in metabolic pathways such as α-linolenic acid metabolism, glycolysis/gluconeogenesis, glycerolipid metabolism, glucagon signaling pathway, glycine, serine and threonine metabolism. Co-enrichment analysis indicated that PFOS exposure may disturb the metabolism pathways of glycerolipid, glycolysis/gluconeogenesis, linoleic acid, steroid biosynthesis, glycine, serine and threonine. The key involved genes included down-regulated Ppp1r3c and Abcd2, and up-regulated Ogdhland Ppp1r3g, and the key metabolites such as increased glycerol 3-phosphate and lactosylceramide were further identified. Both of them were significantly associated with maternal fasting blood glucose (FBG) level. Our findings may provide mechanistic clues for clarifying metabolic toxicity of PFOS in human, especially for susceptible population such as pregnant women. |
| first_indexed | 2024-04-09T23:55:11Z |
| format | Article |
| id | doaj.art-dcbdff6e4e574d6f877afd9963fb12a6 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-09T23:55:11Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
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| series | Environment International |
| spelling | doaj.art-dcbdff6e4e574d6f877afd9963fb12a62023-03-17T04:32:25ZengElsevierEnvironment International0160-41202023-03-01173107851Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysisGuoqi Yu0Jinguo Wang1Yongjie Liu2Tingyu Luo3Xi Meng4Ruiyuan Zhang5Bo Huang6Yan Sun7Jun Zhang8Ministry of Education -Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaSchool of Public Health, Guilin Medical University, Guilin 541001, ChinaMinistry of Education -Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaSchool of Public Health, Guilin Medical University, Guilin 541001, ChinaMinistry of Education -Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaMinistry of Education -Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaSchool of Public Health, Guilin Medical University, Guilin 541001, ChinaSchool of Public Health, Guilin Medical University, Guilin 541001, China; Corresponding authors at: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; School of the Public Health, Guilin Medical University, Guilin 541001, Guangxi, China.Ministry of Education -Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Corresponding authors at: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; School of the Public Health, Guilin Medical University, Guilin 541001, Guangxi, China.Emerging epidemiological evidence has linked per- and polyfluoroalkyl substances (PFAS) exposure could be linked to the disturbance of gestational glucolipid metabolism, but the toxicological mechanism is unclear, especially when the exposure is at a low level. This study examined the glucolipid metabolic changes in pregnant rats treated with relatively low dose perfluorooctanesulfonic acid (PFOS) through oral gavage during pregnancy [gestational day (GD): 1–18]. We explored the molecular mechanisms underlying the metabolic perturbation. Oral glucose tolerance test (OGTT) and biochemical tests were performed to assess the glucose homeostasis and serum lipid profiles in pregnant Sprague-Dawley (SD) rats randomly assigned to starch, 0.03 and 0.3 mg/kg·bw·d groups. Transcriptome sequencing combined with non-targeted metabolomic assays were further performed to identify differentially altered genes and metabolites in the liver of maternal rats, and to determine their correlation with the maternal metabolic phenotypes. Results of transcriptome showed that differentially expressed genes at 0.03 and 0.3 mg/kg·bw·d PFOS exposure were related to several metabolic pathways, such as peroxisome proliferator-activated receptors (PPARs) signaling, ovarian steroid synthesis, arachidonic acid metabolism, insulin resistance, cholesterol metabolism, unsaturated fatty acid synthesis, bile acid secretion. The untargeted metabolomics identified 164 and 158 differential metabolites in 0.03 and 0.3 mg/kg·bw·d exposure groups, respectively under negative ion mode of Electrospray Ionization (ESI-), which could be enriched in metabolic pathways such as α-linolenic acid metabolism, glycolysis/gluconeogenesis, glycerolipid metabolism, glucagon signaling pathway, glycine, serine and threonine metabolism. Co-enrichment analysis indicated that PFOS exposure may disturb the metabolism pathways of glycerolipid, glycolysis/gluconeogenesis, linoleic acid, steroid biosynthesis, glycine, serine and threonine. The key involved genes included down-regulated Ppp1r3c and Abcd2, and up-regulated Ogdhland Ppp1r3g, and the key metabolites such as increased glycerol 3-phosphate and lactosylceramide were further identified. Both of them were significantly associated with maternal fasting blood glucose (FBG) level. Our findings may provide mechanistic clues for clarifying metabolic toxicity of PFOS in human, especially for susceptible population such as pregnant women.http://www.sciencedirect.com/science/article/pii/S0160412023001241Perfluorooctanesulfonic acidGlycolipid metabolismPregnancyMetabolomeTranscriptome |
| spellingShingle | Guoqi Yu Jinguo Wang Yongjie Liu Tingyu Luo Xi Meng Ruiyuan Zhang Bo Huang Yan Sun Jun Zhang Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis Environment International Perfluorooctanesulfonic acid Glycolipid metabolism Pregnancy Metabolome Transcriptome |
| title | Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis |
| title_full | Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis |
| title_fullStr | Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis |
| title_full_unstemmed | Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis |
| title_short | Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis |
| title_sort | metabolic perturbations in pregnant rats exposed to low dose perfluorooctanesulfonic acid an integrated multi omics analysis |
| topic | Perfluorooctanesulfonic acid Glycolipid metabolism Pregnancy Metabolome Transcriptome |
| url | http://www.sciencedirect.com/science/article/pii/S0160412023001241 |
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