Characterization of the Intracellular Calcium Store at the Base of the Sperm Flagellum That Regulates Hyperactivated Motility1

Abstract

Hyperactivated sperm motility is usually characterized by high-amplitude flagellar bends and asymmetrical flagellar beating. There is evidence that an inositol 1,4,5-trisphosphate (IP3) receptor-gated Ca2+ store in the base of the flagellum provides Ca2+ to initiate hyperactivation; however, the identity of the store was not known. Ca2+ stores are membrane-bounded organelles, and the only two membrane-bounded organelles found in this region of sperm are the redundant nuclear envelope (RNE) and mitochondria. Transmission electron micrographs revealed two different compartments of RNE, one enriched with nuclear pores and the other containing few pores but extensive membranous structures with enlarged cisternae. Immunolabeling showed that IP3 receptors and calreticulin are located in the region containing enlarged cisternae. In other cell types, mitochondria adjacent to Ca2+ stores are actively involved in modulating Ca2+ signals by taking up Ca2+ released from stores and also may respond by increasing production of NADH and ATP to support increased energy demand. Nevertheless, bull sperm did not show an increase in NADH when Ca2+ was released from intracellular stores by thapsigargin to induce hyperactivation. Consistently, no net increase in ATP production was detected when sperm were hyperactivated, although ATP was hydrolyzed at a greater rate. Furthermore, blocking Ca2+ efflux from mitochondria by CGP-37157, a specific inhibitor of the mitochondrial Na+/Ca2+ exchanger, did not inhibit the development of hyperactivated motility. We concluded that the intracellular Ca2+ store is the part of RNE that contains enlarged cisternae and that Ca2+ is released directly to the axoneme to trigger hyperactivated motility without the active participation of mitochondria.

Analysis and difference of voltage-dependent anion channel mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia

“…VDAC, as a channel protein, has been validated to mediate ions transport such as Na + , Ca 2+ , Cl − and HCO 3 − . These ions are indispensable not only for acrosomal reaction, but also for sperm motility [36][37][38]. VDAC2 in the plasma membrane of sperm head could affect sperm motility through mediating the transport of these ions.…”

Male Mice That Do Not Express Group VIA Phospholipase A2 Produce Spermatozoa with Impaired Motility and Have Greatly Reduced Fertility

“…Signals that regulate motility of spermatozoa include changes in cAMP and intracellular [Ca 2ϩ ] (27)(28)(29)(30)(31)(32)(33), and both parameters are affected by products of PLA 2 action, which include a free fatty acid and a 2-lysophospholipid. Mice deficient in soluble adenylyl cyclase activity are infertile because of a severe sperm motility defect (20), and both abnormalities also occur in mice null for the catalytic subunit of cAMP-dependent protein kinase A (33).…”

Moving to the beat: a review of mammalian sperm motility regulation

“…Intracellular calcium stores may be involved, particularly in the regulation of hyperactivated motility (Ho and Suarez 2003). However, other than the acrosome, there are no obvious intracellular calcium stores in sperm because, unlike somatic cells, there is no apparent endoplasmic reticulum within the flagellum.…”

“…However, other than the acrosome, there are no obvious intracellular calcium stores in sperm because, unlike somatic cells, there is no apparent endoplasmic reticulum within the flagellum. The redundant nuclear envelope of the sperm neck is one area that has been implicated as a source of intracellular flagellar calcium (Ho and Suarez 2003).…”