Localization, Distribution, and Function of the Calcium‐Sensing Receptor in Sperm

Abstract

ABSTRACT:The intracellular movement of calcium, through calcium channels, plays a major role on sperm cell function. The calcium-sensing receptor (CaSR), a molecular mechanism by which many cells detect changes in extracellular calcium concentration, has not been described in spermatozoa. The aim of this study was to investigate the expression of the CaSR in testicular tissue and sperm cells and the functional consequences of spermatozoid CaSR activation by calcimimetics. CaSR mRNA and protein were identified both in rat testicular tissue and in rat spermatozoa using real-time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. Functionality of CaSR was evaluated by studying the influence of calcimimetic AMG 641 on rat and pig sperm motility. Treatment with AMG 641 100 nM for 1 hour increased rat sperm motility from a score of 1.0 6 0.1 to 3.8 6 0.3 (P , .05). AMG 641 also resulted in a modest but significant increase in the pig sperm motility parameters evaluated by computer-assisted sperm analysis. AMG 641 was effective in a wide range of concentrations but resulted in a more marked effect at 50-100 nM. In addition, AMG 641 did not have any negative effect on sperm viability, which was measured by flow cytometry. In conclusion, our results demonstrate the expression of functional CaSR in testicular tissue and sperm, which can be activated by calcimimetic AMG 641.

Calcium-Sensing Receptor-Mediated Osteogenic and Early-Stage Neurogenic Differentiation in Umbilical Cord Matrix Mesenchymal Stem Cells from a Large Animal Model

“…The same group confirmed these results in human amniotic fluid MSCs [53]. Our data allow us to confirm that CaSR is involved in the osteogenic differentiation of UCM-MSC because the research calcimimetic AMG641 used in the present study is a selective CaSR activator [59], [60]. The different molecular cell responses observed in large and small cell lines, may be due to their different developmental and functional maturity (different commitment status, as discussed above), including possible differences in the CaSR gene structure, gene expression regulatory mechanisms or signal transduction pathways, as previously hypothesized by Martino et al, [13].…”

“…Our data cannot be easily compared with those of the study by Mendoza et al, [58], due to different in vivo versus in vitro adopted experimental approaches. Moreover, AMG641 has been reported as having different effects attending to cell types [60]. Further comparisons can be performed with previous studies reporting the effects of other selective CaSR agonists on the proliferation of fetal-adnexa derived MSCs.…”

The Calcium-Sensing Receptor and the Reproductive System

“…Since a calcimimetic drug (AMG 641) caused a moderate, but significant increase of motility of isolated rat sperms, a role of CaSR in sperm motility was suggested. A similar stimulatory effect on pig sperms mobility indicated expression of CaSR also in male gametes of this species (Mendoza et al, 2012). …”

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats

“…CaSR plays crucial roles in both calcium homeostasis and calcium-independent disorders including diabetes and infertility 1427. CaSR agonists, antagonists, and other drugs mediated through CaSR have been used in the management of many disorders 7.…”

“…Functional CaSR has also been found to be expressed in testicular tissues and sperm cells, which can be activated by calcimimetics. Localization of CaSR is an important contributor to the regulation of cell proliferation and apoptosis 14. It was recently reported that CaSR activation plays a critical role in the apoptosis of cardiomyocytes in diabetes-induced cardiac injury in rats by inducing calcium overload and subsequent activation of mitochondrial and mitogen-activated protein kinase (MAPK) pathways 11.…”