PMID- 35301063 OWN - NLM STAT- MEDLINE DCOM- 20220405 LR - 20230402 IS - 1873-1708 (Electronic) IS - 0890-6238 (Print) IS - 0890-6238 (Linking) VI - 109 DP - 2022 Apr TI - Trichloroethylene modifies energy metabolites in the amniotic fluid of Wistar rats. PG - 80-92 LID - S0890-6238(22)00030-2 [pii] LID - 10.1016/j.reprotox.2022.03.004 [doi] AB - Exposure to trichloroethylene (TCE), an industrial solvent, is associated with several adverse pregnancy outcomes in humans and decreased fetal weight in rats. However, effects of TCE on energy metabolites in amniotic fluid, which have associations with pregnancy outcomes, has not been published previously. In the current exploratory study, timed-pregnant Wistar rats were exposed to 480 mg TCE/kg/day via vanilla wafer or to vehicle (wafer) alone from gestational day (GD) 6-16. Amniotic fluid collected on GD 16 was analyzed for metabolites important in energy metabolism using short chain fatty acid and tricarboxylic acid plus platforms (N = 4 samples/sex/treatment). TCE decreased concentrations of the following metabolites in amniotic fluid for both fetal sexes: 6-phosphogluconate, guanosine diphosphate, adenosine diphosphate, adenosine triphosphate, and flavin adenine dinucleotide. TCE decreased fructose 1,6-bisphosphate and guanosine triphosphate concentrations in amniotic fluid of male but not female fetuses. Moreover, TCE decreased uridine diphosphate-D-glucuronate concentrations, and increased arginine and phosphocreatine concentrations, in amniotic fluid of female fetuses only. No metabolites were increased in amniotic fluid of male fetuses. Pathway analysis suggested that TCE altered folate biosynthesis and pentose phosphate pathway in both sexes. Using metabolite ratios to investigate changes within specific pathways, some ratio alterations, including those in arginine metabolism and phenylalanine metabolism, were detected in females only. Ratio analysis also suggested enzymes, including gluconokinase, as potential TCE targets. Together, results from this exploratory study suggest that TCE differentially modified energy metabolites in amniotic fluid based on sex. These findings may inform future studies of TCE reproductive toxicity. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Su, Anthony L AU - Su AL AD - Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: ansu@umich.edu. FAU - Harris, Sean M AU - Harris SM AD - Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: harrsemi@umich.edu. FAU - Elkin, Elana R AU - Elkin ER AD - Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: elkinela@umich.edu. FAU - Karnovsky, Alla AU - Karnovsky A AD - Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Palmer Commons, 100 Washtenaw Ave #2017, Ann Arbor, MI 48109, USA. Electronic address: akarnovs@med.umich.edu. FAU - Colacino, Justin A AU - Colacino JA AD - Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA; Department of Nutritional Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: colacino@umich.edu. FAU - Loch-Caruso, Rita AU - Loch-Caruso R AD - Department of Environmental Health Sciences, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: rlc@umich.edu. LA - eng GR - P42 ES017198/ES/NIEHS NIH HHS/United States GR - P30 ES017885/ES/NIEHS NIH HHS/United States GR - U24 DK097153/DK/NIDDK NIH HHS/United States GR - T32 ES007062/ES/NIEHS NIH HHS/United States GR - T32 HD079342/HD/NICHD NIH HHS/United States GR - R01 ES028802/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220315 PL - United States TA - Reprod Toxicol JT - Reproductive toxicology (Elmsford, N.Y.) JID - 8803591 RN - 0 (Solvents) RN - 290YE8AR51 (Trichloroethylene) SB - IM MH - Amniotic Fluid/metabolism MH - Animals MH - Female MH - Male MH - Pregnancy MH - Pregnancy Outcome MH - Rats MH - Rats, Wistar MH - Solvents/toxicity MH - *Trichloroethylene/toxicity PMC - PMC9000924 MID - NIHMS1790126 OTO - NOTNLM OT - Amnio acids OT - Amniotic fluid OT - Metabolism OT - Metabolomics OT - Pregnancy OT - Rat OT - Short chain fatty acid OT - Trichloroethylene COIS- Conflicts of Interest The authors declare that no conflicts of interest exist. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/03/19 06:00 MHDA- 2022/04/06 06:00 PMCR- 2023/04/01 CRDT- 2022/03/18 05:39 PHST- 2021/10/03 00:00 [received] PHST- 2022/03/05 00:00 [revised] PHST- 2022/03/11 00:00 [accepted] PHST- 2022/03/19 06:00 [pubmed] PHST- 2022/04/06 06:00 [medline] PHST- 2022/03/18 05:39 [entrez] PHST- 2023/04/01 00:00 [pmc-release] AID - S0890-6238(22)00030-2 [pii] AID - 10.1016/j.reprotox.2022.03.004 [doi] PST - ppublish SO - Reprod Toxicol. 2022 Apr;109:80-92. doi: 10.1016/j.reprotox.2022.03.004. Epub 2022 Mar 15.