| Neonatal diethylstilbestrol exposure alters the metabolic profile of uterine epithelial cells. | |
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MedLine Citation:
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PMID: 22679223 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Developmental exposure to diethylstilbestrol (DES) causes reproductive tract malformations, affects fertility and increases the risk of clear cell carcinoma of the vagina and cervix in humans. Previous studies on a well-established mouse DES model demonstrated that it recapitulates many features of the human syndrome, yet the underlying molecular mechanism is far from clear. Using the neonatal DES mouse model, the present study uses global transcript profiling to systematically explore early gene expression changes in individual epithelial and mesenchymal compartments of the neonatal uterus. Over 900 genes show differential expression upon DES treatment in either one or both tissue layers. Interestingly, multiple components of peroxisome proliferator-activated receptor-γ (PPARγ)-mediated adipogenesis and lipid metabolism, including PPARγ itself, are targets of DES in the neonatal uterus. Transmission electron microscopy and Oil-Red O staining further demonstrate a dramatic increase in lipid deposition in uterine epithelial cells upon DES exposure. Neonatal DES exposure also perturbs glucose homeostasis in the uterine epithelium. Some of these neonatal DES-induced metabolic changes appear to last into adulthood, suggesting a permanent effect of DES on energy metabolism in uterine epithelial cells. This study extends the list of biological processes that can be regulated by estrogen or DES, and provides a novel perspective for endocrine disruptor-induced reproductive abnormalities. |
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Authors:
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Yan Yin; Congxing Lin; G Michael Veith; Hong Chen; Maulik Dhandha; Liang Ma |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-05-31 |
Journal Detail:
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Title: Disease models & mechanisms Volume: 5 ISSN: 1754-8411 ISO Abbreviation: Dis Model Mech Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-01 Completed Date: 2013-04-19 Revised Date: 2013-05-08 |
Medline Journal Info:
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Nlm Unique ID: 101483332 Medline TA: Dis Model Mech Country: England |
Other Details:
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Languages: eng Pagination: 870-80 Citation Subset: IM |
Affiliation:
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Division of Dermatology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adipogenesis
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drug effects,
genetics Animals Animals, Newborn Biological Transport / drug effects Diethylstilbestrol / pharmacology* Epithelial Cells / drug effects, metabolism*, ultrastructure Epithelium / drug effects, metabolism, ultrastructure Female Gene Expression Regulation / drug effects Glucose / metabolism Homeostasis / drug effects Humans Lipid Metabolism / drug effects Metabolic Networks and Pathways / drug effects Metabolome / drug effects*, genetics Mice PPAR gamma / metabolism Uterus / cytology* |
| Grant Support | |
ID/Acronym/Agency:
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ES014482/ES/NIEHS NIH HHS; ES016597/ES/NIEHS NIH HHS; P30 CA91842/CA/NCI NIH HHS; P30 DC004665/DC/NIDCD NIH HHS; UL1RR024992/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/PPAR gamma; 50-99-7/Glucose; 56-53-1/Diethylstilbestrol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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