Mammalian spermatozoa become motile at ejaculation, but before they can fertilize the egg, they must acquire more thrust to penetrate the cumulus and zona pellucida. The forceful asymmetric motion of hyperactivated spermatozoa requires Ca2+ entry into the sperm tail by an alkalinization-activated voltage-sensitive Ca2+-selective current (ICatSper). Hyperactivation requires CatSper1 and CatSper2 putative ion channel genes, but the function of two other related genes (CatSper3 and CatSper4) is not known. Here we show that targeted disruption of murine CatSper3 or CatSper4 also abrogated ICatSper, sperm cell hyperactivated motility and male fertility but did not affect spermatogenesis or initial motility. Direct protein interactions among CatSpers, the sperm specificity of these proteins, and loss of ICatSper in each of the four CatSper−/− mice indicate that CatSpers are highly specialized flagellar proteins.

https://www.pnas.org/content/pnas/104/4/1219.full.pdf

All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility

Loss of forward motility of rabbit epididymal spermatozoa in high K phosphate buffer is in- hibited by taurine, hypotaurine, epinephrine and bovine serum albumin. Pyruvate and lactate also show this effect. The rate of lipid peroxidation in these spermatozoa, as measured by rate of formation of malonaldialdehyde, is also inhibited by these agents. A close linear correlation be- tween percent inert spermatozoa and malondialdehyde was found, which was independent of the rate of peroxidation. Complete cessation of motility was observed at 0.5 nmol malondialdehyde/ iocells in the absence or presence of these agents, which is the same value found in other sus- pending media in a previous study LAlvarez and Storey (1982) Biol. Reprod. 27:1102-11081. Albumin was the most effective agent in preventing loss of motility and inhibiting lipid peroxida- tion. Hypotaurine was the next most effective, followed by taurine, epinephrine, pyruvate and lactate. Hypotaurine reduces the amount of rate of superoxide production, as measured by the rate of reduction of acetylated ferricytochrome c by 0, from rabbit sperm under these conditions and concomitantly reduces inactivation of the superoxide dismutase in these cells. Since superoxide seems to be the major inducer of lipid peroxidation in rabbit sperm, the protective effect of hypo- taurine, which should be readily permeant to the plasma membrane, may be ascribed to scavenging of intracellular superoxide. The mechanism of the protective action of albumin is not known. Rabbit epididymal spermatozoa lose motility over time if Ca2� or Mg2 are omitted from the suspending medium. This loss is not correlated with the rate of lipid peroxidation, which is un- affected by the absence or presence of these ions. The linear correlation between loss of motility and lipid peroxidation no longer holds in the absence of Ca2* and Mg2�, implying motility loss by a different mechanism.

/pdf/taurine-hypotaurine-epinephrine-and-albumin-inhibit-lipid-3idqjxfvuv.pdf

Taurine, hypotaurine, epinephrine and albumin inhibit lipid peroxidation in rabbit spermatozoa and protect against loss of motility.

Mitochondria of spermatozoa are different from the corresponding organelles of somatic cells, in both their morphology and biochemistry. The biochemical differences are essentially related to the existence of specific enzyme isoforms, which are characterized by peculiar kinetic and regulatory properties. As mitochondrial energy metabolism is a key factor supporting several sperm functions, these organelles host critical metabolic pathways during germ cell development and fertilization. Furthermore, spermatozoa can use different substrates, and therefore activate different metabolic pathways, depending on the available substrates and the physico-chemical conditions in which they operate. This versatility is critical to ensure fertilization success. However, the most valuable aspect of mitochondria function in all types of cells is the production of chemical energy in the form of ATP which can be used, in the case of spermatozoa, for sustaining sperm motility. The latter, on the other hand, represents one of the major determinants of male fertility. Accordingly, the presence of structural and functional alterations in mitochondria from asthenozoospermic subjects confirms the important role played by these organelles in energy maintenance of sperm motility. The present study gives an overview of the current knowledge on the energy-producing metabolic pathways operating inside human sperm mitochondria and critically analyse the differences with respect to somatic mitochondria. Such a comparison has also been carried out between the functional characteristics of human sperm mitochondria and those of other mammalian species. A deeper understanding of mitochondrial energy metabolism could open up new avenues of investigation in bioenergetics of human sperm mitochondria, both in physiological and pathological conditions.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2605.2011.01218.x

The role of mitochondria in energy production for human sperm motility.

Rabbit spermatozoa released from the cauda epididymidis into Tris phosphate medium contain- ing KCI or NaCl and 0.4 mM EDTA underwent spontaneous lipid peroxidation during aerobic incubation at 37#{176}C. In the medium containing 130 mM Kand 0 mM Na� (KTP), the rate of lipid peroxidation, as measured by malonaldehyde production, proceeded at a linear rate of 0.045 nmol malonaldehyde/h per 108 cells for 22 h. The motility of these spermatozoa declined with time in medium KTP, with 40% initial forward motility decreasing to zero in 4 h and initial 60% flagellar beating ceasing after 12 h. The percent inert spermatozoa showing no flagellar motion in KTP increased linearly with production of malonaldehyde; all flagellar activity stopped at 0.5 nmol malonaldehyde/10 cells. In the Tris phosphate medium containing 120 mM Naand 10 mM K� (NTP), the percentage of sperm showing forward motility was close to 100% and this declined to 60% after 16 h aerobic incubation. Flagellar beating was not observed. In medium NTP, the rate of lipid peroxidation was 0.0056 nmol malonaldehyde/h per 10 cells, eightfold lower than that observed in KTP. The same linear correlation between malonaldehyde production and percent inert sperm was found as for KTP: 0.5 nmol malonaldehyde/108 cells also corresponded to cessation of flagellar motion. The dependence of motility maintenance on K+ concentration in Tris phosphate medium containing (Na+ + K+)=1 30 mM showed maximal maintenance at 10 mM K+, with a decline at 0 mM K+ and steep decline at K+ concentrations greater than 30 mM. This strong dependence of rabbit sperm peroxidation on ionic composition of the medium is suggested to involve perturbation of the equilibrium between O9 and its conjugate acid HO2', the latter species being the agent of peroxidation.

/pdf/spontaneous-lipid-peroxidation-in-rabbit-epididymal-539bobe9wy.pdf

Spontaneous lipid peroxidation in rabbit epididymal spermatozoa: its effect on sperm motility.

http://www.repro-endo.usz.ch/Documents/fachwissen/andrologielabor/Wong%20et%20al%202001.pdf

Robin Sagadraca

Papers

Sperm motility within the mammalian epididymis: species variation and correlation with free calcium levels in epididymal plasma.