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No country for old sperm: male aging, sperm aging, and external stressors as determinants of sperm quality and fertility

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Fruit flies shed light on male infertility and sperm inviability in humans

It has been said the West is undergoing a male fertility crisis with recent research from the Hebrew University in Israel showing that sperm counts among men have more than halved in the past 40 years. The SPERMAGE projects set out to look for clues as to why.

Health

Declining sperm quality with age is a major cause of male infertility and a problem in many parts of the world including Europe where it has particular relevance as fatherhood is increasingly delayed. Yet there remains poor understanding of both the underlying mechanisms which cause sperm to deteriorate, along with inadequate appreciation of the full consequences of these processes. For example, it is unclear how much of the sperms’ reduced quality is due to advanced male age or the time sperm are stored within male reproductive organs. What is known is that livestock have not undergone a similar decline. The EU-funded Marie Skłodowska-Curie Fellowship project, SPERMAGE, set out to untangle the influence of male ageing and sperm ageing on fertility, reproductive fitness and sperm quality using fly (Drosophila) models. The project found a strong genetic basis to sperm viability and some indication that male ejaculates with a high proportion of viable sperm may sometimes negatively impact female fertility.

Investigating the puzzle of sperm viability variation

The SPERMAGE team collectively brought more than 50 years of reproduction expertise to investigate some of the elements contributing to the puzzle of variation in sperm viability – put simply, why do males not consistently produce high quality ejaculates? The team looked at Drosophila, the genus of fly widely used as models to investigate a range of biological phenomena. These flies are perfect for studies like this as they are easy to rear in large numbers, have short generations and share common genetic pathways with most animals. The team established standardised genotypes by selectively breeding generations in the lab and then investigating the effects of genotype on sperm viability. They assessed the proportion of live and dead sperm in the testes of flies using a staining technique that marks live and dead sperm differently (live sperm stained green, dead stained red) and then tested whether differences in the proportion of live and dead sperm depended on genotype. “Our work found some immediate causes of sperm quality decline and also possible ultimate reasons. For example, while viable sperm benefits competing males, high viability ejaculates may actually cause egg wastage in females by over-stimulating the female reproductive tract for example. So there may be evolutionary trade-offs underway in the fertility process,” says project coordinator, David Hosken.

Further down the line

Currently SPERMAGE’s results contribute chiefly to the EU’s knowledge and skills base. “As we were exploring highly novel areas of research we had to overcome some pretty difficult experimental challenges through intelligent experimental design. One major issue was obtaining enough sperm that we could then isolate and subject to experimental scrutiny,” says Hosken. In the future, as the processes studied are comparable across animals, the results will become increasingly relevant to fundamental and applied research in human ageing, reproductive health and animal breeding. The next step for the team will be to further investigate other possible causes of sperm inviability, along with how some of these underlying causes may interact, including testing putative mechanisms thought to cause age-related fertility declines.

Keywords

SPERMAGE, fertility, ageing, eggs, evolutionary, Drosophila, ejaculates, viability, inviability, genotype, breeding

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