Energy Metabolism in Mammalian Sperm Function

Mammalian spermatozoa require finely tuned energy metabolism to sustain motility, capacitation and ultimate fertilisation. Two primary pathways supply adenosine triphosphate (ATP): glycolysis, operating along the flagellar fibrous sheath, and mitochondrial oxidative phosphorylation (OXPHOS) in the midpiece. Glycolysis affords rapid, local ATP production for flagellar beating, while OXPHOS delivers higher yield under capacitating conditions, supporting hyperactivation and zona pellucida penetration. The balance and interplay between these pathways vary among species and physiological states. During capacitation, sperm undergo biochemical modifications—changes in membrane fluidity, ionic fluxes and protein phosphorylation—each demanding discrete energetic inputs. Reactive oxygen species (ROS), generated primarily by mitochondria, participate in redox signalling yet pose a risk of oxidative damage if unregulated. Emerging evidence has highlighted sperm-specific isoforms of key enzymes, transporters for alternative substrates (pyruvate, citrate) and uncoupling proteins that modulate mitochondrial membrane potential. Disruption of any component—be it glycolytic enzyme function, mitochondrial activity or ROS homeostasis—can compromise motility, capacitation efficacy and fertility. Advances in single-cell metabolomics and live-cell flux analysis now allow dissection of these pathways in real time, offering new targets for diagnosis and treatment of male infertility as well as optimisation of assisted-reproductive technologies across mammalian species.

Research from Nature Portfolio

Recent studies in a porcine model have demonstrated that basal metabolic profiles in spermatozoa directly influence fertilising capacity and early embryo development. Targeted metabolomics revealed that higher levels of glycolysis-derived metabolites correlate with improved motility, in vitro fertilisation rates and embryo progression to blastocyst. Glycolysis emerged as the preferred ATP-generating route in this species, with enhanced embryo yields observed when sperm favour this pathway over OXPHOS. These findings underscore the prognostic value of sperm metabolic status and suggest that modulation of glycolytic flux could refine selection criteria for in vitro fertilisation protocols.

Energy Metabolism in Mammalian Sperm Function publication trend

The graph below shows the total number of articles in energy metabolism in mammalian sperm function across all publications each year (not limited to Nature Index journals).

Technical terms

Glycolysis: Anaerobic breakdown of glucose to pyruvate, yielding ATP in the flagellar compartment.

Oxidative phosphorylation (OXPHOS): Mitochondrial process coupling electron transport to ATP synthesis via proton motive force.

Capacitation: Biochemical and physiological transformation of sperm within the female tract, priming for fertilisation.

Hyperactivation: Enhanced, asymmetrical flagellar beating required for zona pellucida penetration.

Mitochondrial uncoupling proteins (UCPs): Inner membrane carriers that dissipate proton gradient, regulating heat and ROS production.

Hexokinase 1S (HK1S): Spermatogenic cell-specific isoform that catalyses the first step of glycolysis in sperm flagellum.

References

1. Sperm physiology and in vitro fertilising ability rely on basal metabolic activity: insights from the pig model. Communications Biology (2023).
2. Inhibition of Mitochondrial Uncoupling Proteins Arrests Human Spermatozoa Motility without Compromising Viability. Antioxidants (2023).
3. Capacitation induces changes in metabolic pathways supporting motility of epididymal and ejaculated sperm. Frontiers in Cell and Developmental Biology (2023).
4. Spermatogenic cell-specific type 1 hexokinase (HK1S) is essential for capacitation-associated increase in tyrosine phosphorylation and male fertility in mice. PLOS Genetics (2024).