The eutheria-specific miR-290 cluster modulates placental growth and maternal-fetal transport

Development. 2017 Oct 15;144(20):3731-3743. doi: 10.1242/dev.151654. Epub 2017 Sep 21.

Abstract

The vertebrate-specific ESCC microRNA family arises from two genetic loci in mammals: miR-290/miR-371 and miR-302. The miR-302 locus is found broadly among vertebrates, whereas the miR-290/miR-371 locus is unique to eutheria, suggesting a role in placental development. Here, we evaluate that role. A knock-in reporter for the mouse miR-290 cluster is expressed throughout the embryo until gastrulation, when 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 cluster gene (Mirc5) results in reduced trophoblast progenitor cell proliferation and a reduced DNA content in endoreduplicating trophoblast giant cells. The resulting placenta is reduced in size. In addition, the vascular labyrinth is disorganized, with thickening of the maternal-fetal blood barrier and an associated reduction in diffusion. Multiple mRNA targets of the miR-290 cluster microRNAs are upregulated. These data uncover a crucial function for the miR-290 cluster in the regulation of a network of genes required for placental development, suggesting a central role for these microRNAs in the evolution of placental mammals.

Keywords: Mouse; Placenta; Placentation; Trophoblast; miR-290; miR-371; microRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Lineage
  • Cell Proliferation
  • Female
  • Gene Expression Profiling
  • Genotype
  • Giant Cells / cytology
  • Maternal-Fetal Exchange
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics*
  • MicroRNAs / physiology*
  • Multigene Family
  • Placenta / physiology*
  • Pregnancy
  • Sequence Analysis, RNA
  • Trophoblasts / metabolism

Substances

  • MIRN290 microRNA, mouse
  • MicroRNAs