Neonatal diethylstilbestrol exposure alters the metabolic profile of uterine epithelial cells
Year: 2012
Type: article
Abstract: 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.
Source: Disease Models & Mechanisms
DOI: 10.1242/dmm.009076
Institution: Washington University in St. Louis
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,750
Funders: Washington University in St. Louis, Alvin J. Siteman Cancer Center, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Environmental Health Sciences, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1114310655, Research Core Center for Auditory and Vestibular Studies, G299873027, G4790110765, G6377323820, EXTERNAL GENITALIA DEVELOPMENT AND HYPOSPADIAS, Washington University Institute of Clinical and Translational Sciences, Washington University Institute of Clinical and Translational Sciences (UL1), G8242737674, G9000032646, G9000319192, Cancer Center Support Grant, DES and the Regulation of the Uterine Cytodifferentiation
OpenAlex ID: W2154363221