The physiological regulation of sperm motility has become more amenable to investigation since the demonstration that CAMP and calcium play a role in modulating the functioning of the flagellar axoneme. Although the external triggering mechanisms that initiate motility and capacitation are still unknown, evidence supports a modification of the calcium balance by gated Ca2+ channels, accompanied by shifts in the internal pH. Ca2' and pH may in turn act indirectly through CAMP and CAMPdependent kinase (kinase,) to control the phosphorylation state of functional proteins in the flagellar axoneme. The role of calcium is of central importance, but it is clear that several separate Ca2+-dependent mechanisms are involved. Ca2+ controls the curvature of the sperm flagellum and, so, can change the motility of the sperm from progressive swimming to tumbling. Under the appropriate conditions, calcium appears to have the capacity to deactivate motility by activating phosphodiesterase and phosphatase. The deactivating effect of Ca2+ may be offset under some circumstances by coactivation of adenyl cyclase, so phosphorylation of the axoneme and the motility are maintained. The specific factors determining the predominant calcium effect are not yet known, but internal pH of the sperm may play a major role.Key Words: Sperm motility; Mammalian sperm; Mammalian reproduction; Flagellum; Calcium; pH. INTRODUCTIONThis review explores the influences regulating motility in mammalian sperm. Sperm motility depends on a flagellum, the organelle that develops the propulsive force for swimming. The cellular signals that modulate the action of the flagellar motor apparatus are the primary focus of this survey. Evidence is also examined to define the role of the male and female reproductive tracts in controlling sperm motility. To facilitate this review, structure/function relationships in mammalian sperm flagellum are briefly discussed. For the most part, the information included in this review has been obtained from research studies on mammalian sperm to identify the regulatory mechanisms most likely to be of physiological importance in mammalian reproduction. Received and accepted January 24, 1989. MORPHOLOGICAL PARAMETERSMammalian sperm swim by the propulsive action of a single flagellum. The structural foundation of the mammalian sperm flagellum is the 9 + 2 arrangement of microtubules that extends centrally through its entire length. This microtubule arrangement, called the axoneme, is common to all eukaryotic flagella ( Fig. 1) and also to cilia. Surrounding the axoneme are larger fibers, called coarse fibers or outer dense fibers (ODF), that are paired with the 9 outer doublet tubules. These fibers are anchored to the base of the flagellum in a caplike structure known as the connecting piece (CP). From there they taper in diameter along the flagellar length, terminating one-half to three-quarters of the way down the flagellum. The sperm mitochondria are wrapped around the basal one-third of the flagellum and this section is referred ...

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Rat sperm from the cauda epididymis exhibit increased motility, longevity, and a distinct circular pattern of flagellar curvature in response to 5 mM procaine-HCl or 0.1 mM 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), reagents that are thought to play a role in the immobilization of free cellular calcium. Triton X-100-extracted sperm models will exhibit the same pattern of motility and curvature as procaine- or TMB-8-activated cells, but only when calcium is removed by a strong chelating agent, and in the presence of cAMP (3 microM). Demembranated sperm models produced from epididymal rat sperm are quiescent unless cAMP is added. In these sperm models, the presence or absence of free calcium mediates a transition in flagellar curvature. The increased activity of the procaine-treated intact cells was not accompanied by a change in cellular ATP content, nor was ATP availability the limiting factor in the quiescent sperm. Therefore, the increased motility produced by procaine is probably mediated by a fall in free intracellular Ca2+ accompanied by a rise in cAMP. Our finding that calcium controls the curvature of sperm flagella may explain altered patterns of flagellar beating, such as the hyperactivated motility that sperm exhibit in the female reproductive tract.

Bovine sperm, extracted with 0.1% Triton X-100, frozen at -20 degrees C for 48-120 hours, and thawed, disintegrated by microtubule sliding when 1 mM MgATP was added. Microtubules and outer dense fibers (ODFs) were usually extruded in groups or "bundles". A total of 44.5% of the cells extruded two distinct bundles, one from each side of the connecting piece, exhibiting opposite curvatures. Only one bundle was observed in 46.2% of the cells, and 9.2% showed no signs of sliding. Transmission electron microscopy (T.E.M.) showed one group consisting of the 4,5-6,7 elements, with the 9,1,2 elements on the other side of the axoneme making up the other bundle. T.E.M. revealed that when only one side of the axoneme had extruded elements, they were always from the 4,5-6,7 group. The remainder of the axoneme (8,9,1,2,3 and the central pair) was left relatively intact, suggesting a difference in the sliding response of the nine pairs of axonemal microtubules. These results indicate a predisposition for sliding between elements 7 and 8 over that between doublets 2 and 3, perhaps due to a disparity in activation thresholds. Also, both Ni2+ and Cd2+ appear to selectively block activation of 2-3 interdoublet sliding. Incubation with 0.25 mM Ni2+ prior to adding MgATP modified the percentages of sliding patterns: 8.6% demonstrated two-sided extrusion, 58.2% showed one-sided, and 33.2% had no extruded bundles. Again, when half the axoneme was missing, it was always the 4,5-6,7 group. Ten micromolar Cd2+ altered the sliding pattern similarly to Ni2+, with 28% two-sided extrusion, 55.9% one-sided extrusion and 16.1% with no extruded bundles. Either pretreatment regimen impeded extrusion of the 9,1,2 group in a high percentage of cells, compared to untreated cells. This specific inhibition of the 9,1,2 side by Ni2+ or Cd2+ is especially significant since Ni2+ also inhibits spontaneous wave initiation in bull sperm (Lindemann et al.: Journal of Cell Biology 87:420-426, 1980), and both Ni2+ and Cd2+ reportedly block the flagellar Ca(2+)-response in rat sperm (Lindemann and Goltz: Cell Motility and the Cytoskeleton 10:420-431, 1988; Lindemann et al.: Cell Motility and the Cytoskeleton 20:316-324, 1991).

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