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Some men have sperm with poor motility and the aim of the spermNMR project is to understand why this is and how it is related to sperm metabolism.

Sperm use chemical fuels called substrates to power their motility. These fuel are consumed by two main methods – Oxidative phosphorylation (OxPhos) and Glycolysis that vary in their efficiency of energy production.

The first is highly efficient but requires oxygen to operate whereas the later generates less energy but oxygen is not needed. This is important as the availability of oxygen and chemical fuels varies considerably with location in the female reproductive system.

Additionally, sperm undergo a number of changes in readiness for fertilisation, including a change in motility called hyperactivation. How much energy sperm obtain from OxPhos, Glycolysis or proportions of both is part of an ongoing debate within the scientific community that has been confused by the use of sperm from other species or differing methods used to measure energy production.

Understanding how sperm respond to changes in energy requirements as they travel to the egg will help us to identify why sperm with poor motility fail to function.

We are using carbon-13 labelled molecules to track sperm energy metabolism by Magnetic Resonance Spectroscopy (MRS). The chemical reactions that occur during metabolism cause the carbon-13 spectrum to change as some MRS peaks shrink when molecules are consumed, whilst other peaks appear and grow as products are formed.

Normally it takes hours to capture a carbon-13 spectrum, however, our laboratory has a state of the art technology called hyperpolarisation that increases the sensitivity of the MRS signal by thousands of times. Using this technology we can obtain a carbon-13 spectrum in less than a second so we can watch the MRS signals change in real time as one molecule is converted into another.

In the journal Scientific Reports we have published [Ref 1] the first ever use of hyperpolarised MRS to study sperm metabolism. The figure below shows a sequence of carbon-13 spectra captured every second as the signals change in response to metabolism of carbon-13 labelled pyruvate.

On the right hand side, the size of the peaks are shown for pyruvate (blue) and the metabolic products lactate (orange) and bicarbonate (green). At the end of the sequence a red spectrum shows the accumulated signal.

We observed that both lactate and bicarbonate signals are being produced from pyruvate showing that sperm use both OxPhos (bicarbonate) and glycolysis (lactate) energy production methods. Furthermore, we found that increased sperm motility led to increased lactate and bicarbonate signals appearing in the spectrum.

The sperm remained alive throughout the experiment so we could repeat it one hour later.

Using this technology allows us to measure ‘snapshots’ of sperm metabolism consuming substrates as they respond to the rapid biological and environmental change they encounter as they progress towards fertilising an egg.

We hope that this will help us understand the metabolic differences between sperm with normal and poor motility that could lead to new treatment options to improve male fertility.

Ref 1: Reynolds, S., Ismail, N. F. B., Calvert, S. J., Pacey, A. A. & Paley, M. N. J. Evidence for Rapid Oxidative Phosphorylation and Lactate Fermentation in Motile Human Sperm by Hyperpolarized 13C Magnetic Resonance Spectroscopy. Sci Rep 7, 4322, doi:10.1038/s41598-017-04146-1 (2017).