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

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.

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“…insulin release. In contrast, the third a 2 -AR subtype, a 2B , does not play a major role in the regulation of secretion but may have its most important function in angiogenesis of the placenta during embryonic development (37).…”

Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility

“…The generation of these mouse lines has been described previously in detail [20,35]. Genotypes were confirmed by subtype-specific polymerase chain reactions (with a TProfessional Basic Thermocycler, Biometra) performed with genomic DNA isolated from tail biopsies as described previously [36]. Animals were housed in a temperature-and humidity-controlled room at a 12-h …”

α2-Adrenoceptors do not Mediate Neuroprotection in Acute Ischemic Stroke in Mice

“…The generation of mice with targeted deletions of a 2 -adrenoceptors was reported in detail elsewhere (Gilsbach and Hein, 2008). All genotypes were backcrossed onto a C57BL/6J genetic background for > 8 to 12 generations (Philipp et al, 2002b). Eight to 12-week-old male and female a 2 -adrenoceptors À/À mice and wild-type (WT) littermates were used.…”