Journal Article

Metabolomic Response of Human Embryonic Stem Cell–Derived Germ-like Cells After Exposure to Steroid Hormones

Franklin D. West, W. Matthew Henderson, Ping Yu, Jeong-Yeh Yang, Steven L. Stice and Mary Alice Smith

in Toxicological Sciences

Volume 129, issue 1, pages 9-20
Published in print September 2012 | ISSN: 1096-6080
Published online May 2012 | e-ISSN: 1096-0929 | DOI:
Metabolomic Response of Human Embryonic Stem Cell–Derived  Germ-like Cells After Exposure to Steroid Hormones

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To assess the potential risks of human exposure to endocrine active compounds (EACs), the mechanisms of toxicity must first be identified and characterized. Currently, there are no robust in vitro models for identifying the mechanisms of toxicity in germ cells resulting from EAC exposure. Human embryonic stem cells can differentiate into numerous functional cell types including germ-like cells (GLCs). These cells possess characteristics indicative of a germ cell state, suggesting they offer a novel system to investigate the consequences of chemical exposure on normal germ cell processes. To characterize these processes, a metabolomic-based approach was employed to determine the response of GLCs following exposure to 0.001, 0.01, 0.1, 1, 10, or 100µM estradiol, testosterone, or progesterone for 48h. Following exposure, cellular extracts underwent gas chromatography coupled with mass spectrometry analysis. Models were then constructed using principal component analysis on acquired spectra to discriminate among steroid hormones as well as doses for each hormone. t-test comparisons generated a preliminary list of metabolites that were statistically significant in GLC’s biochemical response to these steroid hormones. Steroid hormone exposures caused fluxes in intracellular pathways such as amino acid synthesis and metabolism, fatty acid synthesis, as well as cholesterol and lipoprotein metabolism. Further pathway analysis, based on these identified metabolites, will aid in modeling the response of GLCs to endogenous steroid hormones and allow for identification of biomarkers delineating germ cell-based developmental and reproductive pathways.

Keywords: metabolomics; germ cell; stem cell; steroid hormones

Journal Article.  7877 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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