Ketone Body beta-Hydroxy-Butyrate Sustains Progressive Motility in Capacitated Human Spermatozoa: A Possible Role in Natural Fertility

Background Calorie restriction is recognized as a useful nutritional approach to improve the endocrine derangements and low fertility profile associated with increased body weight. This is particularly the case for dietary regimens involving ketosis, resulting in increased serum levels of ketone bodies such as beta-hydroxy-butyrate (beta-HB). In addition to serum, beta-HB is detected in several biofluids and beta-HB levels in the follicular fluid are strictly correlated with the reproductive outcome in infertile females. However, a possible direct role of ketone bodies on sperm function has not been addressed so far. Methods Semen samples were obtained from 10 normozoospermic healthy donors attending the University Andrology Unit as participants in an infertility survey programme. The effect of beta-HB on cell motility in vitro was evaluated on isolated spermatozoa according to their migratory activity in a swim-up selection procedure. The effect of beta-HB on spermatozoa undergone to capacitation was also assessed. Results Two hours of exposure to beta-HB, 1 mM or 4 mM, proved to be ineffective in modifying the motility of freshly ejaculated spermatozoa isolated according to the migratory activity in a swim-up procedure (all p values > 0.05). Differently, sperm maintenance in 4 mM beta-HB after capacitation was associated with a significantly higher percentage of sperm cells with progressive motility compared to beta-HB-lacking control (respectively, 67.6 +/- 3.5% vs. 55.3 +/- 6.5%, p = 0.0158). Succinyl-CoA transferase inhibitor abolished the effect on motility exerted by beta-HB, underpinning a major role for this enzyme. Conclusion Our results suggest a possible physiological role for beta-HB that could represent an energy metabolite in support of cell motility on capacitated spermatozoa right before encountering the oocyte.