Neonatal DES treatment dramatically alters the metabolic pathways in uterine epithelium (UE) cells, a mechanism that can affect homeostasis of the female reproductive tract
2012 Study 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.
Key Points
- Neonatal DES exposure alters uterine cell metabolism predominantly in the epithelium.
- Neonatal DES exposure alters adipogenesis and lipid metabolism in the uterine epithelium (UE).
- DES induces PPARγ-dependent adipogenesis in the UE.
- Neonatal DES exposure alters glucose transport and metabolism in the UE
Neonatal DES exposure alters metabolic pathways in adult UE.
Sources and more information
- Full study (free access) : Neonatal diethylstilbestrol exposure alters the metabolic profile of uterine epithelial cells, Journal List, Dis Model Mech, NCBI PubMed PMC3484869, 2012 Nov.
- DES alters uterine gene expression primarily in the epithelium featured image credit PMC3484869/figure/f1-0050870.
DES DIETHYLSTILBESTROL RESOURCES
- Source DES and epigenetics studies.
- Diethylstilbestrol DES studies by topics.