GATA-2 AND GATA-3 REGULATE TROPHOBLAST-SPECIFIC GENE-EXPRESSION IN-VIVO

We previously demonstrated that the zinc finger transcription factors GATA-2 and GATA-3 are expressed in trophoblast giant cells and that th ey regulate transcription from the mouse placental lactogen I gene pro moter in a transfected trophoblast cell line. We present evidence here that both of these factors regulate transcription of the placental la ctogen I gene, as well as the related proliferin gene, in trophoblast giant cells in vivo. Placentas lacking GATA-3 accumulate placental lac togen I and proliferin mRNAs to a level 50% below that reached in the wild-type placenta. Mutation of the GATA-2 gene had a similar effect o n placental lactogen I expression, but led to a markedly greater reduc tion (5- to 6-fold) in proliferin gene expression; Placentas lacking G ATA-2 secrete significantly less angiogenic activity than wild-type pl acentas as measured in an endothelial cell migration assay, consistent with a reduction in expression of the angiogenic hormone proliferin. Furthermore, within the same uterus the decidual tissue adjacent to mu tant placentas displays markedly reduced neovascularization compared t o the decidual tissue next to wild-type placentas. These results indic ate that GATA-2 and GATA-3 are important in vivo regulators of trophob last-specific gene expression and placental function, and reveal a dif ference in the effect of these two factors in regulating the synthesis of related placental hormones.