EPA Science Inventory

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

Citation:

West, F., Matt Henderson, P. Yu, J. Yang, S. Stice, AND M. Smith. Metabolomic Response of Human Embryonic Stem Cell Derived Germ-like Cells after Exposure to Steroid Hormones. TOXICOLOGICAL SCIENCES. Society of Toxicology, 129(1):9-20, (2012).

Description:

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 (hESCs) 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 100 µM estradiol (E2), testosterone (T) or progesterone (P) for 48 hrs. Following exposure, cellular extracts underwent GC/MS 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.

Purpose/Objective:

see description

URLs/Downloads:

http://toxsci.oxfordjournals.org/   Exit

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 05/16/2012
Completion Date: 05/16/2012
Record Last Revised: 12/26/2012
Record Created: 09/27/2012
Record Released: 09/27/2012
OMB Category: Other
Record ID: 246555

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL EXPOSURE RESEARCH LAB

ECOSYSTEMS RESEARCH DIVISION