Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta

Dev Biol. 2002 Oct 15;250(2):358-73. doi: 10.1016/s0012-1606(02)90773-6.


Mammalian embryos have an intimate relationship with their mothers, particularly with the placental vasculature from which embryos obtain nutrients essential for growth. It is an interesting vascular bed because maternal vessel number and diameter change dramatically during gestation and, in rodents and primates, the terminal blood space becomes lined by placental trophoblast cells rather than endothelial cells. Molecular genetic studies in mice aimed at identifying potential regulators of these processes have been hampered by lack of understanding of the anatomy of the vascular spaces in the placenta and the general nature of maternal-fetal vascular interactions. To address this problem, we examined the anatomy of the mouse placenta by preparing plastic vascular casts and serial histological sections of implantation sites from embryonic day (E) 10.5 to term. We found that each radial artery carrying maternal blood into the uterus branched into 5-10 dilated spiral arteries located within the metrial triangle, populated by uterine natural killer (uNK) cells, and the decidua basalis. The endothelial-lined spiral arteries converged together at the trophoblast giant cell layer and emptied into a few straight, trophoblast-lined "canals" that carried maternal blood to the base of the placenta. Maternal blood then percolated back through the intervillous space of the labyrinth toward the maternal side of the placenta in a direction that is countercurrent to the direction of the fetal capillary blood flow. Trophoblast cells were found invading the uterus in two patterns. Large cells that expressed the trophoblast giant cell-specific gene Plf (encoding Proliferin) invaded during the early postimplantation period in a pattern tightly associated with spiral arteries. These peri/endovascular trophoblast were detected only approximately 150-300 microm upstream of the main giant cell layer. A second type of widespread interstitial invasion in the decidua basalis by glycogen trophoblast cells was detected after E12.5. These cells did not express Plf, but rather expressed the spongiotrophoblast-specific gene Tpbp. Dilation of the spiral arteries was obvious between E10.5 and E14.5 and was associated with a lack of elastic lamina and smooth muscle cells. These features were apparent even in the metrial triangle, a site far away from the invading trophoblast cells. By contrast, the transition from endothelium-lined artery to trophoblast-lined (hemochorial) blood space was associated with trophoblast giant cells. Moreover, the shaping of the maternal blood spaces within the labyrinth was dependent on chorioallantoic morphogenesis and therefore disrupted in Gcm1 mutants. These studies provide important insights into how the fetoplacental unit interacts with the maternal intrauterine vascular system during pregnancy in mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / anatomy & histology
  • Corrosion Casting
  • Female
  • Glycoproteins / genetics
  • Glycoproteins / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Maternal-Fetal Exchange / physiology*
  • Mice
  • Mice, Inbred ICR
  • Mice, Mutant Strains
  • Neovascularization, Physiologic
  • Neuropeptides / genetics
  • Neuropeptides / physiology
  • Nuclear Proteins
  • Placenta / blood supply*
  • Placenta / embryology
  • Placental Circulation / physiology*
  • Pregnancy
  • Prolactin
  • Species Specificity
  • Transcription Factors
  • Trophoblasts / cytology*
  • Trophoblasts / physiology*


  • GCM1 protein, human
  • Gcm1 protein, mouse
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Neuropeptides
  • Nuclear Proteins
  • Prl2c2 protein, mouse
  • Transcription Factors
  • Prolactin