%0 Journal Article %1 Philipp.2002 %A Philipp, M. %A Brede, M. E. %A Hadamek, K. %A Gessler, M. %A Lohse, M. J. %A Hein, L. %D 2002 %J Nat Genet %K AMP/analysis Animals Cyclic Death/genetics Deletion Development/genetics Embryo;Mammalian/metabolism Embryonic;Fetal Female Fetal Gene Heart/embryology Kinases/metabolism Mice Mice;Mutant Mitogen-Activated Placenta/blood Pregnancy Protein Receptors;Adrenergic;alpha-2/deficiency/*physiology Strains supply/*metabolism %N 3 %P 311--315 %T Placental alpha(2)-adrenoceptors control vascular development at the interface between mother and embryo %V 31 %X 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 alpha(2)-adrenoceptors, which are activated by adrenaline and noradrenaline, are important regulators of placental structure and function. Mice with deletions in the genes encoding alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors died between embryonic days 9.5 and 11.5 from a severe defect in yolk-sac and placenta development. In wildtype placentae, alpha(2)-adrenoceptors are abundantly expressed in giant cells, which secrete angiogenic factors to initiate development of the placental vascular labyrinth. In placentae deficient in alpha(2A)-, alpha(2B)- and alpha(2C)-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 alpha(2)-adrenoceptors is required for placenta and yolk-sac vascular development. Thus, alpha(2)-adrenoceptors are essential at the placental interface between mother and embryo to establish the circulatory system of the placenta and thus maintain pregnancy.

@article{Philipp.2002, 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 alpha(2)-adrenoceptors, which are activated by adrenaline and noradrenaline, are important regulators of placental structure and function. Mice with deletions in the genes encoding alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors died between embryonic days 9.5 and 11.5 from a severe defect in yolk-sac and placenta development. In wildtype placentae, alpha(2)-adrenoceptors are abundantly expressed in giant cells, which secrete angiogenic factors to initiate development of the placental vascular labyrinth. In placentae deficient in alpha(2A)-, alpha(2B)- and alpha(2C)-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 alpha(2)-adrenoceptors is required for placenta and yolk-sac vascular development. Thus, alpha(2)-adrenoceptors are essential at the placental interface between mother and embryo to establish the circulatory system of the placenta and thus maintain pregnancy.}, added-at = {2013-01-29T13:47:26.000+0100}, author = {Philipp, M. and Brede, M. E. and Hadamek, K. and Gessler, M. and Lohse, M. J. and Hein, L.}, biburl = {https://www.bibsonomy.org/bibtex/2124624d224995e122580a2e469b8cbb7/ebch}, interhash = {c18335216a63f26bf5ecabafe422a7db}, intrahash = {124624d224995e122580a2e469b8cbb7}, journal = {Nat Genet}, keywords = {AMP/analysis Animals Cyclic Death/genetics Deletion Development/genetics Embryo;Mammalian/metabolism Embryonic;Fetal Female Fetal Gene Heart/embryology Kinases/metabolism Mice Mice;Mutant Mitogen-Activated Placenta/blood Pregnancy Protein Receptors;Adrenergic;alpha-2/deficiency/*physiology Strains supply/*metabolism}, number = 3, pages = {311--315}, timestamp = {2013-01-29T13:47:30.000+0100}, title = {Placental alpha(2)-adrenoceptors control vascular development at the interface between mother and embryo}, volume = 31, year = 2002 }