News Release

Reversing age-related fertility decline in male fruit flies: the crucial role of seminal fluid

Peer-Reviewed Publication

University of Oxford

Fruit fly sperm

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Sperm inside male testes and seminal vesicles in a fruit fly. Credit: Krish Sanghvi

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Credit: Krish Sanghvi.

As males age their reproductive success typically declines. A study in fruit flies, led by University of Oxford researchers has found that while old males do produce fewer offspring than young males, this is not because they have fewer sperm, but it is due to seminal fluid limitation. This study highlights the importance of the seminal fluid in reproductive success and may have crucial implications for improving animal fertility and IVF.

It is widely recognized that as males age, their fertility typically declines (a phenomenon known as reproductive senescence), often due to a reduction in the quantity and/or quality of sperm in older males. However, this new study led by researchers in Oxford’s Department of Biology which investigated sequential matings in fruit flies (Drosophila melanogaster), found that while old males produce fewer offspring than young males, it is not due to a lack of sperm.

The researchers found that old males have more sperm than young males due to accumulation over time and they also transfer similar numbers or more sperm to females during mating. Yet, surprisingly, females store fewer sperm of old males which results in fewer offspring and the reproductive decline observed in old males.

The research suggests this could be due to females ejecting a higher proportion of sperm from old males shortly after mating or due to the poor seminal fluid quality of old males. Seminal fluid is the non-sperm component of the ejaculate (often called seminal plasma in humans), that contains a cocktail of nutrients and proteins that are crucial for ensuring fertilisation, sperm storage, and egg laying.

The impact of ejaculate quality on fertility is likely more pronounced in polygamous species, where males mate with multiple females, as ejaculate production is energetically costly. In such species, investing in both the quantity and quality of ejaculate is more crucial than in monogamous species, where males mate with only a single female.

To further investigate whether seminal fluid indeed was limiting old male reproductive success, the researchers supplemented females with seminal fluid (but not sperm) of young males. This supplementation was achieved by mating females with a transgenic, seminal fluid-only producing male, which do not produce any sperm. Here they found that this supplementation rescued the reproductive success of aged males, such that old and young males had similar numbers of offspring. Hence, old males benefitted from the supplemented seminal fluid of young males.

This also indicates a major benefit of polygamous mating to the second male - the seminal fluid of previous males can improve their fertility. Such mechanisms might explain why the last male to mate fathers most offspring in some species. Importantly, the study also showed that the observed decline in male fertility through the polygamous mating sequence disappear when females were supplemented with seminal fluid.

Lead author Dr Krish Sanghvi (Department of Biology, University of Oxford) said: “We show that different components of the ejaculate – sperm versus seminal fluid – decline at different rates with age and through a mating sequence. Old males do have lower reproductive output than young males as expected, but this is likely driven by seminal fluid deterioration, decline in sperm viability, and via differential sperm storage by females, rather than a decline in sperm numbers with age.”

The results emphasise the under-appreciated role that seminal fluid quantity and quality play in male fertility in polygamous species. These results have important consequences for sexual conflict and sexual selection, whereby female fitness is not only determined by a male’s mating history or male age, but also their interaction. Importantly, the results show that declines in male reproductive output are not permanent and can be reversed by the presence of sufficient, good quality seminal fluid. This interplay between sperm and seminal fluid has crucial implications for improving animal fertility as well as possible implications for In Vitro Fertilisation (IVF).

Senior author Dr Irem Sepil (Department of Biology, University of Oxford) said: “Future studies can determine whether the technique of seminal fluid supplementation can be applied to humans, a species where the importance of seminal fluid in fertility is already well established. For example, seminal fluid transplantation, where the seminal fluid of healthy fertile donors is used to supplement the sperm of infertile donors, might become a reliable method to improve fertility.”

Dr Krish Sanghvi added: “Our next steps are to determine whether it is just the presence of seminal fluid or its age too that affects male fertility, and to understand the role of female sperm ejection in the increased sperm retention of young males.”

Notes to editors

The paper ‘Reproductive output of old males is limited by seminal fluid, not sperm number’ has been published in Evolution Letters: https://academic.oup.com/evlett/advance-article/doi/10.1093/evlett/qrae071/7943589

Images and a video are available for use, credit Krish Sanghvi.

Interviews with the corresponding author are available on request. Media contact:

Dr Krish Sanghvi: krish.sanghvi@biology.ox.ac.uk

Dr Irem Sepil: irem.sepil@biology.ox.ac.uk

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