The extracellular calcium-sensing receptor is expressed in the cumulus-oocyte complex in mammals and modulates oocyte meiotic maturation.
Abstract: 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.
Publication Date: 2009-06-03 PubMed ID: 19494043DOI: 10.1530/REP-09-0078Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the expression and functional role of the extracellular calcium-sensing receptor (CASR) in the maturation process of oocyte meiosis in horses, demonstrating that this pathway aids oocyte meiosis in larger mammals.
About Extracellular Calcium-Sensing Receptor (CASR)
- The extracellular calcium-sensing receptor (CASR) senses changes in the extracellular calcium ion concentration, which is crucial for maintaining calcium homeostasis in our bodies.
- CASR can be found in cells that deal with calcium regulation, as well as in human oocytes, as previously reported in other studies.
CASR Expression in Horses
- The study, performed on horses, confirms that CASR is expressed in equine oocytes and cumulus cells, similar to humans.
- Its expression was confirmed via Western-blot analysis and confocal microscopy, showing its presence on the plasma membrane and within the cytoplasm during all stages of oocyte meiosis.
Functional Role of CASR and Its Effect on Oocyte Meiosis
- The study discovered that by employing an allosteric effector called NPS R-467 under the right conditions (2.92 mM external Ca2+), they could increase the rate of oocyte maturation. This effect, however, was lessened if pre-treated with a CASR antagonist, NPS 2390.
- This indicates that the effect of NPS R-467 requires a certain threshold of external calcium to stimulate oocyte maturation as it had no effect under suboptimal external calcium conditions (0.5 mM).
- Oocytes treated with NPS R-467 showed increased CASR staining at the plasmalemma and reduced in the cytosol.
- Additionally, the treatment increased the activity of a signaling protein called Mitogen-Activated Protein Kinase (MAPK), also known as ERK, within the cumulus cells and oocytes.
Conclusions and Significance
- This research uncovers a previously unknown signal transduction pathway that influences the maturation of oocytes in mammals.
- These findings could provide valuable insights into fertility studies and contribute towards the development of potential treatment options for infertility in large mammals.
Cite This Article
APA
De Santis T, Casavola V, Reshkin SJ, Guerra L, Ambruosi B, Fiandanese N, Dalbies-Tran R, Goudet G, Dell'Aquila ME.
(2009).
The extracellular calcium-sensing receptor is expressed in the cumulus-oocyte complex in mammals and modulates oocyte meiotic maturation.
Reproduction, 138(3), 439-452.
https://doi.org/10.1530/REP-09-0078 Publication
Researcher Affiliations
- Department of Animal Production, University of Bari, 70010 Valenzano, Bari, Italy.
MeSH Terms
- Adamantane / analogs & derivatives
- Adamantane / pharmacology
- Aniline Compounds / pharmacology
- Animals
- Cells, Cultured
- Cumulus Cells / drug effects
- Cumulus Cells / metabolism
- Female
- Gene Expression / drug effects
- Horses
- Immunohistochemistry
- Mammals / genetics
- Mammals / metabolism
- Mammals / physiology
- Meiosis / drug effects
- Meiosis / genetics
- Meiosis / physiology
- Oocytes / drug effects
- Oocytes / metabolism
- Oocytes / physiology
- Oogenesis / drug effects
- Oogenesis / genetics
- Oogenesis / physiology
- Quinoxalines / pharmacology
- RNA, Messenger / analysis
- RNA, Messenger / metabolism
- Receptors, Calcium-Sensing / genetics
- Receptors, Calcium-Sensing / metabolism
- Receptors, Calcium-Sensing / physiology
- Tissue Distribution
Citations
This article has been cited 8 times.- Yang R, Ji CL, Zhang M, Zhang J, Yuan HJ, Luo MJ, Jiao GZ, Tan JH. Role of calcium-sensing receptor in regulating activation susceptibility of postovulatory aging mouse oocytes. J Reprod Dev 2023 Aug 11;69(4):185-191.
- Liu H, Zhou D, Liu C, Zhuan Q, Luo Y, Mo X, Fu X, Hou Y. The Calcium-Sensing Receptor Is Involved in Follicle-Stimulating Hormone-Induced Cumulus Expansion in in vitro Cultured Porcine Cumulus-Oocyte Complexes. Front Cell Dev Biol 2021;9:625036.
- Refaat B, El-Boshy M. Effects of supraphysiological vitamin D(3) (cholecalciferol) supplement on normal adult rat ovarian functions. Histochem Cell Biol 2021 Jun;155(6):655-668.
- Nadeau JH. Do Gametes Woo? Evidence for Their Nonrandom Union at Fertilization. Genetics 2017 Oct;207(2):369-387.
- Ellinger I. The Calcium-Sensing Receptor and the Reproductive System. Front Physiol 2016;7:371.
- Martino NA, Reshkin SJ, Ciani E, Dell'Aquila ME. Calcium-sensing receptor-mediated osteogenic and early-stage neurogenic differentiation in umbilical cord matrix mesenchymal stem cells from a large animal model. PLoS One 2014;9(11):e111533.
- Martino NA, Lange-Consiglio A, Cremonesi F, Valentini L, Caira M, Guaricci AC, Ambruosi B, Sciorsci RL, Lacalandra GM, Reshkin SJ, Dell'Aquila ME. Functional expression of the extracellular calcium sensing receptor (CaSR) in equine umbilical cord matrix size-sieved stem cells. PLoS One 2011 Mar 17;6(3):e17714.
- Li GW, Wang QS, Hao JH, Xing WJ, Guo J, Li HZ, Bai SZ, Li HX, Zhang WH, Yang BF, Yang GD, Wu LY, Wang R, Xu CQ. The functional expression of extracellular calcium-sensing receptor in rat pulmonary artery smooth muscle cells. J Biomed Sci 2011 Feb 11;18(1):16.
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