DES interacts with ERRα, ERRβ, and ERRγ to suppress coactivator binding and transcription from a reporter gene. DES controls the differentiation of trophoblast cells in culture and in utero
2001 Study Abstract
The orphan nuclear receptor ERR beta is expressed in undifferentiated trophoblast stem cell lines and extraembryonic ectoderm, and genetic ablation of ERR beta results in abnormal trophoblast proliferation and precocious differentiation toward the giant cell lineage.
Here, we show that the synthetic estrogen diethylstilbestrol (DES) promotes coactivator release from ERR beta and inhibits its transcriptional activity. Strikingly, treatment of trophoblast stem cells with DES led to their differentiation toward the polyploid giant cell lineage. In addition, DES-treated pregnant mice exhibited abnormal early placenta development associated with an overabundance of trophoblast giant cells and an absence of diploid trophoblast.
These results define a novel pathway for DES action and provide evidence for steroidlike control of trophoblast development.
Sources and more information
- Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR beta, Genes and development, NCBI PubMed PMC312665, 2001 Apr.
- Effect of DES on the morphology of trophoblast tissues featured image credit NCBI.