학술논문
The Calcium-Sensing Receptor Is Essential for Calcium and Bicarbonate Sensitivity in Human Spermatozoa
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
Source
Journal of Clinical Endocrinology & Metabolism. April 2021, Vol. 106 Issue 4, p1775, 18 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Fertilization is the last step in a complex series of events starting with spermatogenesis and sperm maturation in the testis and epididymis. Ejaculation introduces the sperm to the female environment [...]
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: This work aimed to investigate the role of CaSR in human spermatozoa. Methods: We identified CaSR in human spermatozoa and characterized the response to CaSR agonists on intracellular calcium, acrosome reaction, and 3',5'-cyclic adenosine 5'-monophosphate (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 free ionized calcium ([Ca.sup.2+]) and [Mg.sup.2+]. Activators of CaSR augmented the effect of sperm-activating signals such as the response to HC[O.sub.3.sup.-] and the acrosome reaction, whereas spermatozoa from men with a loss-of-function mutation in CASR had a diminished response to HC[O.sub.3.sup.-], lower progesterone-mediated calcium influx, and were less likely to undergo the acrosome reaction in response to progesterone or [Ca.sup.2+]. CaSR activation increased cAMP through soluble adenylyl cyclase (sAC) activity and increased calcium influx through CatSper. Moreover, external [Ca.sup.2+] or [Mg.sup.2+] was indispensable for HC[O.sub.3.sup.-] activation of sAC. Two male patients with a CASR loss-of-function mutation in exon 3 presented with normal sperm counts and motility, whereas a patient with a lossof-function mutation in exon 7 had low sperm count, motility, and morphology. Conclusion: CaSR is important for the sensing of [Ca.sup.2+], [Mg.sup.2+], and HC[O.sub.3.sup.-] in spermatozoa, and loss-of-function may impair male sperm function. Key Words: calcium, fertility, reproduction, CaSR, bicarbonate
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: This work aimed to investigate the role of CaSR in human spermatozoa. Methods: We identified CaSR in human spermatozoa and characterized the response to CaSR agonists on intracellular calcium, acrosome reaction, and 3',5'-cyclic adenosine 5'-monophosphate (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 free ionized calcium ([Ca.sup.2+]) and [Mg.sup.2+]. Activators of CaSR augmented the effect of sperm-activating signals such as the response to HC[O.sub.3.sup.-] and the acrosome reaction, whereas spermatozoa from men with a loss-of-function mutation in CASR had a diminished response to HC[O.sub.3.sup.-], lower progesterone-mediated calcium influx, and were less likely to undergo the acrosome reaction in response to progesterone or [Ca.sup.2+]. CaSR activation increased cAMP through soluble adenylyl cyclase (sAC) activity and increased calcium influx through CatSper. Moreover, external [Ca.sup.2+] or [Mg.sup.2+] was indispensable for HC[O.sub.3.sup.-] activation of sAC. Two male patients with a CASR loss-of-function mutation in exon 3 presented with normal sperm counts and motility, whereas a patient with a lossof-function mutation in exon 7 had low sperm count, motility, and morphology. Conclusion: CaSR is important for the sensing of [Ca.sup.2+], [Mg.sup.2+], and HC[O.sub.3.sup.-] in spermatozoa, and loss-of-function may impair male sperm function. Key Words: calcium, fertility, reproduction, CaSR, bicarbonate