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Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERRβ
Open accessAbstract
The orphan nuclear receptor ERRβ is expressed in undifferentiated trophoblast stem cell lines and extraembryonic ectoderm, and genetic ablation of ERRβ 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 ERRβ 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.
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The nuclear receptor superfamily: the second decade
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90199-x · Cited by 6,964
Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us?
Couse, J. F., & Korach, K. S. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0370 · Cited by 2,045
Cited by
EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals
Gore, A. C., Chappell, V. A., Fenton, S. E., Flaws, J. A., Nadal, A., Prins, G. S., Toppari, J., & Zoeller, R. T. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1010 · Cited by 2,407
Nuclear Receptors and Lipid Physiology: Opening the X-Files
Chawla, A., Repa, J. J., Evans, R. M., & Mangelsdorf, D. J. (2001) · Science · doi:10.1126/science.294.5548.1866 · Cited by 2,085
Schreiber, S. N., Emter, R., Hock, M. B., Knutti, D., Cardenas, J., Podvinec, M., Oakeley, E. J., & Kralli, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308686101 · Cited by 658
Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor α.
Luo, J., Sladek, R., Carrier, J., Bader, J.-A., Richard, D., & Giguère, V. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.7947-7956.2003 · Cited by 370
Self-citationAll-trans retinoic acid is a ligand for the orphan nuclear receptor RORβ
Stehlin-Gaon, C., Willmann, D., Zeyer, D., Sanglier, S., Van Dorsselaer, A., Renaud, J.-P., Moras, D., & Schüle, R. (2003) · Nature Structural & Molecular Biology · doi:10.1038/nsb979 · Cited by 231
Metadata
- Authors
- Tremblay, G. B., Kunath, T., Bergeron, D., Lapointe, L., Champigny, C., Bader, J.-A., Rossant, J., & Giguère, V.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2001-04-01
- Volume
- 15
- Issue
- 7
- Pages
- 833-838
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2112980664
- Cited by
- 255
- References
- 2
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Tremblay, G. B., Kunath, T., Bergeron, D., Lapointe, L., Champigny, C., Bader, J.-A., Rossant, J., & Giguère, V. (2001). Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERRβ. Genes & Development. https://doi.org/10.1101/gad.873401
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