Abstract
Poor sperm motility is a common cause of male infertility for which there are no empirical therapies. Sperm motility is powered by adenosine triphosphate but the relative importance of lactate fermentation and Oxidative Phosphorylation (OxPhos) is debated. To study the relationship between energy metabolism and sperm motility we used dissolution Dynamic Nuclear Polarization (dDNP) for the first time to show the rapid conversion of 13C1-pyruvate to lactate and bicarbonate, indicating active glycolytic and OxPhos metabolism in sperm. The magnitude of both lactate and bicarbonate signals were positively correlated with the concentration of progressively motile sperm. After controlling for sperm concentration, increased progressive sperm motility generated more pyruvate conversion to lactate and bicarbonate. The technique of dDNP allows ‘snapshots’ of sperm metabolism to be tracked over the different stages of their life. This may provide help to uncover the causes of poor sperm motility and suggest new approaches for novel treatments or therapies.
Highlights
Proteomic analysis of the human sperm head and flagellum shows that sperm are highly differentiated in terms of their protein functions, with the tail and mid-piece being dominated by www.nature.com/scientificreports/
The conclusions are confused by the use of differing species, with variations in the structural details of head and tail[13, 14], dominance of energy pathway, the preferred substrate used for generating adenosine triphosphate (ATP) and whether ATP diffuses from the mid-piece into the tail[4]
Non-human sperm has been incubated with 13C-glucose and the results shown that both lactate fermentation and Oxidative phosphorylation are active[16, 17]
Summary
Proteomic analysis of the human sperm head and flagellum (including the mid-piece) shows that sperm are highly differentiated in terms of their protein functions, with the tail and mid-piece being dominated by www.nature.com/scientificreports/. The extent to which sperm use internal stores of metabolites, or rely on an exogenous supply from the external environment is debated[15] To help resolve this debate, isotopically labelled substrates can be used to track a metabolic pathway depending on the location of the isotope label. Once the target molecules have become hyperpolarized the sample is rapidly returned to room temperature for use in experiments (Fig. 2) Combining it with 13C labelled molecules allows in vivo monitoring of metabolism kinetics by rapidly acquiring a series of MRS spectra over a short time window, without the interfering background signals experienced in 1H MRS22. We show for the first time the relative flux of hyperpolarized 13C labelled pyruvate through lactate fermentation and OxPhos and their relationship to sperm motility
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