Tremblay G B, Kunath T, Bergeron D, Lapointe L, Champigny C, Bader J A, Rossant J, Giguère V
Department of Research and Development, SignalGene, Inc., Montréal, Québec H2M 2N9, Canada.
Genes Dev. 2001 Apr 1;15(7):833-8. doi: 10.1101/gad.873401.
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.
孤儿核受体ERRβ在未分化的滋养层干细胞系和胚外外胚层中表达，ERRβ的基因敲除会导致滋养层细胞增殖异常并过早地向巨细胞谱系分化。在此，我们表明合成雌激素己烯雌酚（DES）促进ERRβ释放共激活因子并抑制其转录活性。令人惊讶的是，用DES处理滋养层干细胞会导致它们向多倍体巨细胞谱系分化。此外，经DES处理的怀孕小鼠表现出早期胎盘发育异常，伴有滋养层巨细胞过多和二倍体滋养层细胞缺失。这些结果定义了DES作用的一条新途径，并为滋养层发育的类固醇样调控提供了证据。
