GSE95687
The eutherian-specific miR-290/miR-371 cluster modulates placental growth and maternal-fetal transport
A family of vertebrate-specific microRNAs called the ESCC microRNAs regulates proliferation and differentiation of embryonic stem cells. The ESCC microRNAs arise from two genetic loci in mammals, the miR-290/miR-371 and miR-302 loci. While the miR-302 locus is found broadly among vertebrates, the miR-290/miR-371 locus is unique to eutherian species, suggesting a role in placental development. Here, we evaluate that role. A knockin reporter for the mouse miR-290 gene is expressed throughout the embryo until gastrulation, at which time it becomes specifically expressed in extraembryonic tissues and the germline. In the placenta, expression is limited to the trophoblast lineage, where it remains highly expressed until birth. Deletion of the miR-290 gene results in reduced trophoblast progenitor cell proliferation and a reduced DNA content in endoreduplicating trophoblast giant cells. A reduction in placental size precedes a reduction in fetal size and prenatal death of most knockout embryos. The vascular labyrinth shows disorganization with thickening of the barrier between maternal and fetal blood associated with reduced diffusion of a radioactive tracer. Multiple mRNA targets of the cluster miRNAs are upregulated. Together, these data uncover a critical function for the miR-290 in the regulation of a network of genes required for normal placental development, suggesting a central role for this microRNA cluster in the evolution of eutherian species. Overall design: mRNA expression in miR-290 knockout and wild-type placenta.