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dc.contributor.authorBagchi, Gargien_US
dc.contributor.authorZhang, Yijingen_US
dc.contributor.authorWaxman, David J.en_US
dc.date.accessioned2012-01-11T16:55:02Z
dc.date.available2012-01-11T16:55:02Z
dc.date.copyright2010
dc.date.issued2010-6-18
dc.identifier.citationBagchi, Gargi, Yijing Zhang, David J Waxman. "Impact of methoxyacetic acid on mouse Leydig cell gene expression" Reproductive Biology and Endocrinology 8:65. (2010)
dc.identifier.issn1477-7827
dc.identifier.urihttps://hdl.handle.net/2144/3143
dc.description.abstractBACKGROUND. Methoxyacetic acid (MAA) is the active metabolite of the widely used industrial chemical ethylene glycol monomethyl ether, which is associated with various developmental and reproductive toxicities, including neural toxicity, blood and immune disorders, limb degeneration and testicular toxicity. Testicular toxicity is caused by degeneration of germ cells in association with changes in gene expression in both germ cells and Sertoli cells of the testis. This study investigates the impact of MAA on gene expression in testicular Leydig cells, which play a critical role in germ cell survival and male reproductive function. METHODS. Cultured mouse TM3 Leydig cells were treated with MAA for 3, 8, and 24 h and changes in gene expression were monitored by genome-wide transcriptional profiling. RESULTS. A total of 3,912 MAA-responsive genes were identified. Ingenuity Pathway analysis identified reproductive system disease, inflammatory disease and connective tissue disorder as the top biological functions affected by MAA. The MAA-responsive genes were classified into 1,366 early responders, 1,387 mid-responders, and 1,138 late responders, based on the time required for MAA to elicit a response. Analysis of enriched functional clusters for each subgroup identified 106 MAA early response genes involved in transcription regulation, including 32 genes associated with developmental processes. 60 DNA-binding proteins responded to MAA rapidly but transiently, and may contribute to the downstream effects of MAA seen for many mid and late response genes. Genes within the phosphatidylinositol/phospholipase C/calcium signaling pathway, whose activity is required for potentiation of nuclear receptor signaling by MAA, were also enriched in the set of early MAA response genes. In contrast, many of the genes responding to MAA at later time points encode membrane proteins that contribute to cell adhesion and membrane signaling. CONCLUSIONS. These findings on the progressive changes in gene expression induced by MAA in a cultured Leydig cell model may help elucidate signaling pathways that lead to the testicular pathophysiological responses induced by MAA exposure and may identify useful biomarkers of MAA toxicity.en_US
dc.description.sponsorshipNational Institutes of Health (5 P42 ES07381); Boston University (Superfund Research Program)en_US
dc.language.isoen
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2010 Bagchi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.titleImpact of methoxyacetic acid on mouse Leydig cell gene expressionen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/1477-7827-8-65
dc.identifier.pmid20565877
dc.identifier.pmcid2909983


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Copyright 2010 Bagchi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2010 Bagchi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.