Letter | Published:

Placental α2-adrenoceptors control vascular development at the interface between mother and embryo

Nature Genetics volume 31, pages 311315 (2002) | Download Citation

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Abstract

A substantial percentage of human pregnancies are lost as spontaneous abortions after implantation. This is often caused by an inadequately developed placenta. Proper development of the placental vascular system is essential to nutrient and gas exchange between mother and developing embryo. Here we show that α2-adrenoceptors, which are activated by adrenaline and noradrenaline, are important regulators of placental structure and function. Mice with deletions in the genes encoding α2A-, α2B- and α2C-adrenoceptors died between embryonic days 9.5 and 11.5 from a severe defect in yolk-sac and placenta development. In wildtype placentae, α2-adrenoceptors are abundantly expressed in giant cells, which secrete angiogenic factors to initiate development of the placental vascular labyrinth. In placentae deficient in α2A-, α2B- and α2C-adrenoceptors, the density of fetal blood vessels in the labyrinth was markedly lower than normal, leading to death of the embryos as a result of reduced oxygen and nutrient supply. Basal phosphorylation of the extracellular signal–regulated kinases ERK1 and ERK2 was also lower than normal, suggesting that activation of the mitogen-activated protein kinase (MAP kinase) pathway by α2-adrenoceptors is required for placenta and yolk-sac vascular development. Thus, α2-adrenoceptors are essential at the placental interface between mother and embryo to establish the circulatory system of the placenta and thus maintain pregnancy.

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Acknowledgements

We thank N. Schumacher, C. Arnolt, M. Babl and G. Wolz-Curtaz for technical assistance, and D. Drenckhahn for drawing our attention to abnormalities in the development of embryonic blood vessels in the placenta. This study was supported by the Deutsche Forschungsgemeinschaft.

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Affiliations

  1. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, 97078 Würzburg, Germany.

    • Melanie Philipp
    • , Marc E. Brede
    • , Kerstin Hadamek
    • , Martin J. Lohse
    •  & Lutz Hein
  2. Theodor-Boveri-Institut für Biowissenschaften, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany.

    • Manfred Gessler

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The authors declare no competing financial interests.

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Correspondence to Lutz Hein.

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DOI

https://doi.org/10.1038/ng919

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