Premium
Metabolic Biomarkers of Prenatal Alcohol Exposure in Human Embryonic Stem Cell–Derived Neural Lineages
Author(s) -
Palmer Jessica A.,
Poenitzsch Ashley M.,
Smith Susan M.,
Conard Kevin R.,
West Paul R.,
Cezar Gabriela G.
Publication year - 2012
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2011.01732.x
Subject(s) - embryoid body , metabolome , embryonic stem cell , neural stem cell , biology , metabolite , metabolomics , progenitor cell , stem cell , endocrinology , microbiology and biotechnology , biochemistry , adult stem cell , bioinformatics , gene
Background Fetal alcohol spectrum disorders ( FASD ) are a leading cause of neurodevelopmental disability. The mechanisms underlying FASD are incompletely understood, and biomarkers to identify those at risk are lacking. Here, we perform metabolomic analysis of embryoid bodies and neural lineages derived from human embryonic stem ( hES ) cells to identify the neural secretome produced in response to ethanol ( E t OH ) exposure. Methods WA 01 and WA 09 hES cells were differentiated into embryoid bodies, neural progenitors, or neurons. Cells along this progression were cultured for 4 days with 0, 0.1, or 0.3% E t OH . Supernatants were subjected to C 18 chromatography followed by ESI ‐ QTOF ‐ MS . Features were annotated using public databases, and the identities of 4 putative biomarkers were confirmed with purified standards and comparative MS / MS . Results EtOH treatment induced statistically significant changes to metabolite abundance in human embryoid bodies (180 features), neural progenitors (76 features), and neurons (42 features). There were no shared significant features between different cell types. Fifteen features showed a dose–response to E t OH . Four chemical identities were confirmed: l ‐thyroxine, 5′‐methylthioadenosine, and the tryptophan metabolites, l ‐kynurenine and indoleacetaldehyde. One feature with a putative annotation of succinyladenosine was significantly increased in both E t OH treatments. Additional features were selective to E t OH treatment but were not annotated in public databases. Conclusions EtOH exposure induces statistically significant changes to the metabolome profile of human embryoid bodies, neural progenitors, and neurons. Several of these metabolites are normally present in human serum, suggesting their usefulness as potential serum FASD biomarkers. These findings suggest the biochemical pathways that are affected by E t OH in the developing nervous system and delineate mechanisms of alcohol injury during human development.