Placental alpha(2)-adrenoceptors control vascular development at
the interface between mother and embryo
M. Philipp, M. Brede, K. Hadamek, M. Gessler, M. Lohse, and L. Hein. Nat Genet, 31 (3):
311-5(July 2002)Philipp, Melanie Brede, Marc E Hadamek, Kerstin Gessler, Manfred
Lohse, Martin J Hein, Lutz Comparative Study Research Support, Non-U.S.
Gov't United States Nature genetics Nat Genet. 2002 Jul;31(3):311-5.
Epub 2002 Jun 17..
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.
Philipp, Melanie Brede, Marc E Hadamek, Kerstin Gessler, Manfred
Lohse, Martin J Hein, Lutz Comparative Study Research Support, Non-U.S.
Gov't United States Nature genetics Nat Genet. 2002 Jul;31(3):311-5.
Epub 2002 Jun 17.
%0 Journal Article
%1 Philipp2002
%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, Embryonic Female Fetal Gene Heart/embryology Kinases/metabolism Mammalian/metabolism Mice Mitogen-Activated Mutant Placenta/blood Pregnancy Protein Strains alpha-2/deficiency/*physiology and supply/*metabolism Receptor Adrenergic
%N 3
%P 311-5
%T Placental alpha(2)-adrenoceptors control vascular development at
the interface between mother and embryo
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12068299
%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{Philipp2002,
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 = {2010-12-14T18:12:02.000+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/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {c18335216a63f26bf5ecabafe422a7db},
intrahash = {124624d224995e122580a2e469b8cbb7},
issn = {1061-4036 (Print) 1061-4036 (Linking)},
journal = {Nat Genet},
keywords = {AMP/analysis Animals Cyclic Death/genetics Deletion Development/genetics Embryo, Embryonic Female Fetal Gene Heart/embryology Kinases/metabolism Mammalian/metabolism Mice Mitogen-Activated Mutant Placenta/blood Pregnancy Protein Strains alpha-2/deficiency/*physiology and supply/*metabolism Receptor Adrenergic},
month = Jul,
note = {Philipp, Melanie Brede, Marc E Hadamek, Kerstin Gessler, Manfred
Lohse, Martin J Hein, Lutz Comparative Study Research Support, Non-U.S.
Gov't United States Nature genetics Nat Genet. 2002 Jul;31(3):311-5.
Epub 2002 Jun 17.},
number = 3,
pages = {311-5},
shorttitle = {Placental alpha(2)-adrenoceptors control vascular development at the
interface between mother and embryo},
timestamp = {2010-12-14T18:22:42.000+0100},
title = {Placental alpha(2)-adrenoceptors control vascular development at
the interface between mother and embryo},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12068299},
volume = 31,
year = 2002
}