Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

The calcium-sensing receptor is essential for calcium and bicarbonate sensitivity in human spermatozoa

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{4a0904517533402097b852d9488cc453,
title = "The calcium-sensing receptor is essential for calcium and bicarbonate sensitivity in human spermatozoa",
abstract = "CONTEXT: The calcium-sensing receptor (CaSR) is essential to maintain a stable calcium concentration in serum. Spermatozoa are exposed to immense changes in concentrations of CaSR ligands such as calcium, magnesium, and spermine during epididymal maturation, in the ejaculate, and in the female reproductive environment. However, the role of CaSR in human spermatozoa is unknown.OBJECTIVE AND DESIGN: We identified CaSR in human spermatozoa and characterized the response to CaSR agonists on intracellular calcium, acrosome reaction, and cAMP in spermatozoa from men with either loss-of-function or gain-of-function mutations in CASR and healthy donors.RESULTS: CaSR is expressed in human spermatozoa and is essential for sensing extracellular Ca 2+ and Mg 2+. Activators of CaSR augmented the effect of sperm activating signals such as the response to HCO3- and the acrosome reaction, while spermatozoa from men with a loss-of-function mutation in CASR had a diminished response to HCO3-, lower progesterone-mediated calcium influx, and were less likely to undergo the acrosome reaction in response to progesterone or Ca 2+. CaSR activation increased cAMP through soluble adenylyl cyclase (sAC) activity and increased calcium influx through CatSper. Moreover, external Ca 2+ or Mg 2+ was indispensable for HCO3- activation of sAC. Two male patients with CASR loss-of-function mutation in exon 3 present with normal sperm counts and motility, while a patient with a loss-of-function mutation in exon 7 had low sperm count, motility, and morphology.CONCLUSION: CaSR is important for the sensing of Ca 2+, Mg 2+, and HCO3 - in spermatozoa, and loss-of-function may impair male sperm function.",
keywords = "bicarbonate, calcium, CaSR, fertility, reproduction",
author = "Boisen, {Ida Marie} and Anders Rehfeld and Iris Mos and Poulsen, {Nadia Nicholine} and Nielsen, {John Erik} and Peter Schwarz and Lars Rejnmark and Steen Dissing and Pernille Bach-Mortensen and Anders Juul and Hans Br{\"a}uner-Osborne and Beate Lanske and {Blomberg Jensen}, Martin",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine",
year = "2021",
month = mar,
day = "25",
doi = "10.1210/clinem/dgaa937",
language = "English",
volume = "106",
pages = "e1775--e1792",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The/Endocrine Society",
number = "4",

}

RIS

TY - JOUR

T1 - The calcium-sensing receptor is essential for calcium and bicarbonate sensitivity in human spermatozoa

AU - Boisen, Ida Marie

AU - Rehfeld, Anders

AU - Mos, Iris

AU - Poulsen, Nadia Nicholine

AU - Nielsen, John Erik

AU - Schwarz, Peter

AU - Rejnmark, Lars

AU - Dissing, Steen

AU - Bach-Mortensen, Pernille

AU - Juul, Anders

AU - Bräuner-Osborne, Hans

AU - Lanske, Beate

AU - Blomberg Jensen, Martin

N1 - Publisher Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine

PY - 2021/3/25

Y1 - 2021/3/25

N2 - CONTEXT: The calcium-sensing receptor (CaSR) is essential to maintain a stable calcium concentration in serum. Spermatozoa are exposed to immense changes in concentrations of CaSR ligands such as calcium, magnesium, and spermine during epididymal maturation, in the ejaculate, and in the female reproductive environment. However, the role of CaSR in human spermatozoa is unknown.OBJECTIVE AND DESIGN: We identified CaSR in human spermatozoa and characterized the response to CaSR agonists on intracellular calcium, acrosome reaction, and cAMP in spermatozoa from men with either loss-of-function or gain-of-function mutations in CASR and healthy donors.RESULTS: CaSR is expressed in human spermatozoa and is essential for sensing extracellular Ca 2+ and Mg 2+. Activators of CaSR augmented the effect of sperm activating signals such as the response to HCO3- and the acrosome reaction, while spermatozoa from men with a loss-of-function mutation in CASR had a diminished response to HCO3-, lower progesterone-mediated calcium influx, and were less likely to undergo the acrosome reaction in response to progesterone or Ca 2+. CaSR activation increased cAMP through soluble adenylyl cyclase (sAC) activity and increased calcium influx through CatSper. Moreover, external Ca 2+ or Mg 2+ was indispensable for HCO3- activation of sAC. Two male patients with CASR loss-of-function mutation in exon 3 present with normal sperm counts and motility, while a patient with a loss-of-function mutation in exon 7 had low sperm count, motility, and morphology.CONCLUSION: CaSR is important for the sensing of Ca 2+, Mg 2+, and HCO3 - in spermatozoa, and loss-of-function may impair male sperm function.

AB - CONTEXT: The calcium-sensing receptor (CaSR) is essential to maintain a stable calcium concentration in serum. Spermatozoa are exposed to immense changes in concentrations of CaSR ligands such as calcium, magnesium, and spermine during epididymal maturation, in the ejaculate, and in the female reproductive environment. However, the role of CaSR in human spermatozoa is unknown.OBJECTIVE AND DESIGN: We identified CaSR in human spermatozoa and characterized the response to CaSR agonists on intracellular calcium, acrosome reaction, and cAMP in spermatozoa from men with either loss-of-function or gain-of-function mutations in CASR and healthy donors.RESULTS: CaSR is expressed in human spermatozoa and is essential for sensing extracellular Ca 2+ and Mg 2+. Activators of CaSR augmented the effect of sperm activating signals such as the response to HCO3- and the acrosome reaction, while spermatozoa from men with a loss-of-function mutation in CASR had a diminished response to HCO3-, lower progesterone-mediated calcium influx, and were less likely to undergo the acrosome reaction in response to progesterone or Ca 2+. CaSR activation increased cAMP through soluble adenylyl cyclase (sAC) activity and increased calcium influx through CatSper. Moreover, external Ca 2+ or Mg 2+ was indispensable for HCO3- activation of sAC. Two male patients with CASR loss-of-function mutation in exon 3 present with normal sperm counts and motility, while a patient with a loss-of-function mutation in exon 7 had low sperm count, motility, and morphology.CONCLUSION: CaSR is important for the sensing of Ca 2+, Mg 2+, and HCO3 - in spermatozoa, and loss-of-function may impair male sperm function.

KW - bicarbonate

KW - calcium

KW - CaSR

KW - fertility

KW - reproduction

U2 - 10.1210/clinem/dgaa937

DO - 10.1210/clinem/dgaa937

M3 - Journal article

C2 - 33340048

VL - 106

SP - e1775-e1792

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 4

ER -

ID: 61593564