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The extracellular calcium-sensing receptor is expressed in the cumulus–oocyte complex in mammals and modulates oocyte meiotic maturation

¹ Department of Animal Production, University of Bari, 70010 Valenzano, Bari, Italy² Department of General and Environmental Physiology, University of Bari, 70126 Bari, Italy³ INRA, UMR85 Physiologie de la Reproduction et des Comportements, CNRS UMR6175, Université de Tours, Haras Nationaux, 37380 Nouzilly, France

Correspondence should be addressed to M E Dell'Aquila; Email: e.dellaquila{at}veterinaria.uniba.it

The extracellular calcium-sensing receptor (CASR) plays an important role in cells involved in calcium (Ca²⁺) homeostasis by directly sensing changes in the extracellular Ca²⁺ ion concentration. We previously reported the localization and quantitative expression of CASR protein in human oocytes. In this study, we examined the expression and the functional role of CASR during oocyte meiotic maturation in a large mammal animal model, the horse. As in humans, CASR protein was found to be expressed in equine oocytes and cumulus cells. Western-blot analysis revealed a single 130 kDa band in denuded oocytes and a doublet of 130–120 kDa in cumulus cells. CASR labeling was observed by confocal microscopy in cumulus cells and in oocytes on the plasma membrane and within the cytoplasm at all examined stages of meiosis. Functionally, the CASR allosteric effector NPS R-467, in the presence of 2.92 mM external Ca²⁺, increased oocyte maturation rate in a dose-dependent manner and its stimulatory effect was attenuated by pre-treatment with the CASR antagonist NPS 2390. NPS R-467 had no effect in suboptimal external Ca²⁺ (0.5 mM), indicating that it requires higher external Ca²⁺ to promote oocyte maturation. In oocytes treated with NPS R-467, CASR staining increased at the plasmalemma and was reduced in the cytosol. Moreover, NPS R-467 increased the activity of MAPK, also called ERK, in cumulus cells and oocytes. These results provide evidence of a novel signal transduction pathway modulating oocyte meiotic maturation in mammals in addition to the well-known systemic hormones.