Spectroscopic Probes of Energy Regulation & Metabolism (SPERM): Using High Resolution MR spectroscopy to identify biomarkers of male fertility

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Approximately 20% of young men have poor quality semen and in 50% of couples undergoing in vitro fertilisation (IVF) there is a problem with the sperm from the male partner. Whilst often the problem is because the male has a low sperm count, sometimes it is because his sperm don't swim very well. In such cases, sperm can be injected into his partner's eggs to help fertilisation happen (a process called Intra-cytoplasmic Sperm Injection or ICSI). But this adds to the cost of infertility treatment and is not always funded by the NHS. Currently there are no effective therapies to improve poor sperm motility, but to be able to give sperm a 'boost' might avoid the need for high-tech procedures such as ICSI in preference to less technical ones, or could avoid the need for assisted conception altogether if the therapy was very successful.Unfortunately we know very little about the way that sperm generate the energy necessary for their tail to beat and power them forwards. There are a number of ways they could do this and a range of different 'fuels' they could burn. Therefore, in this project, we propose to use some of the techniques developed by radiologists to examine the energy pathways used by cancer cells to develop new chemotherapy treatments. These techniques rely on detecting the molecular signature of atoms when they are placed in a magnetic field and are very similar to the technology used by doctors to scan a patient to see inside them (MRI). We have already developed a method to prepare sperm and place them inside the scanner and pilot data suggests that we can see key molecules involved in the production of sperm energy. In addition, we have also added some labelled 'fuels' to the sperm to watch how they use them. This suggests our techniques work and now we plan to undertake a more comprehensive analysis of sperm from different men.We will obtain semen from men with different fertilities and prepare their sperm to be scanned under different conditions. We will examine whether we can see differences in the molecules used to make and provide sperm energy between men whose sperm swim well and those whose sperm swim badly. In addition, we will also attempt to separate good swimming sperm from poor swimming sperm in the same man, to see if we can detect differences. If we can, then this may lead to two clinical developments.First, it may allow us to develop a better diagnostic test of sperm motility that is easier and cheaper to perform than the current method. At the moment, in order to diagnose male infertility related to poor sperm motility, a scientist has to observe the motility of sperm using a light microscope. This is labour intensive, prone to error and has developed little since the 1950s. A new test based on the presence or absence of one of more metabolite signals (or combination of signals) could improve this and lead to cost savings for the NHS.Second, if our techniques are able to identify deficiencies in the sperm energy molecules, this opens up the possibility of undertaking further research to devise potential cures. We suggest that this might be possible through one or more of the following four ways: (a) developing drugs that could be taken by the man or woman in the weeks and months prior to conception; (b) advice about specific foods or nutritional supplements to enhance sperm motility; (c) the development of sperm-motility stimulating lubricants or pessaries that could be used by the couple during sex; or (d) sperm-motility stimulating culture media that could be used in IVF and other assisted conception technologies.In conclusion, we propose that our research has the potential to provide a better understanding of how sperm make and use energy to swim. By filling that gap in knowledge, and by developing a new collaboration between fertility specialists and radiologists, we think we have the potential to radically change the diagnosis and treatment of male infertility.