Trichloroethylene Metabolite S-(1,2-Dichlorovinyl)-l-cysteine Stimulates Changes in Energy Metabolites and Amino Acids in the BeWo Human Placental Trophoblast Model during Syncytialization

• DOI: 10.1021/acs.chemrestox.3c00007
• Publication Date: 2023-05-10T23:59:50Z
• Authors: Anthony L. Su; Sean M. Harris; Elana R. Elkin; Alla Karnovsky; Justin Colacino; Rita Karen Loch-C...
• Keywords: Aspartic Acid; Pregnancy; Placenta; Colforsin; Humans; Matrix Metalloproteinase 2; Female; Oleic Acids; Cysteine; Amino Acids; Trichloroethylene; Trophoblasts

Syncytialization, the fusion of cytotrophoblasts into an epithelial barrier that constitutes maternal–fetal interface, is a crucial event placentation. This process characterized by distinct changes to amino acid and energy metabolism. A metabolite industrial solvent trichloroethylene (TCE), S-(1,2-dichlorovinyl)-l-cysteine (DCVC), modifies metabolism abundance in HTR-8/SVneo extravillous trophoblasts. In current study, we investigated DCVC-induced acids during forskolin-stimulated syncytialization BeWo cells, human villous trophoblastic cell line models vitro. cells were exposed forskolin at 100 μM for 48 h stimulate syncytialization. During syncytialization, also treated with DCVC 0 (control), 10, or 20 μM. Following treatment, targeted metabolomics platform, “Tricarboxylic Acid Plus”, was used identify acids. treatment decreased oleic acid, aspartate, proline, uridine diphosphate (UDP), UDP-d-glucose, monophosphate, cytidine monophosphate relative forskolin-only controls, but did not increase any measured metabolite. Notable stimulated absence included increased adenosine guanosine as well aspartate glutamate. Pathway analysis revealed multiple pathways sugar metabolisms altered alone Analysis ratios metabolites within exposure changed same different direction compared alone. Building off our findings, found extracellular matrix metalloproteinase-2, which downstream signaling, underwent acid. Together, metabolic suggest potential mechanisms could impact pregnancy.