Only one of the millions of male sperm cells that set off to fertilise the female egg cell reaches and unites with its target. The name of the game is: first come, first serve! Even better if unwanted competition falls by the wayside. Scientists at Ulm University and the University of California San Francisco (UCSF) have discovered that sticky protein fibres 'catch' poor-quality and damaged sperm and therefore make it easier for the female immune defence to clear them. This might provide their healthy competitors with a significant advantage in the fight for the biological pole position in the sperm race to the female egg cell.
These 'sperm traps' consist of so-called amyloid fibrils. These are fibrous structures of assembled proteins forming 'sticky' insoluble protein aggregates. 'Up until now, all we knew about these sticky protein fibres in semen was that they facilitate the attachment of the AIDS virus to its target cells and thus boost the infection,' explains Professor Jan Münch from the Institute of Molecular Virology in Ulm. He and the Director of the Institute, Professor Frank Kirchhoff, were the ones who discovered the infection-promoting effect of those amyloid fibrils in semen 10 years ago. Together with his research colleagues in California, Münch has now uncovered a natural biological function of these protein fibres.
'We were able to prove that amyloid fibrils in semen inhibit the movement of damaged and redundant sperm. They bind to the unfit sperm cells and immobilise them. These are then quickly swallowed and cleared away by macrophages, the scavenger cells of the immune system,' elaborates Nathallie Sandi-Monroy. The doctoral candidate from Ulm shares the lead authorship of the study with her Californian colleagues Nadia R. Roan and Nargis Kohgadai. The scientific paper was recently published in the renowned journal eLife. 'It looks like these protein fibrils help with sperm selection and therefore give the healthy sperm cells an advance in terms of reproduction,' Professor Münch summarises the results.
The fibrils facilitate the disposal of not needed sperms
The amyloid fibrils also facilitate quicker disposal of excess semen that is unfit for reproduction or not needed any more. To the female organism, male sperm cells are primarily foreign invaders with high antigen potential, which challenge the immune system. Thus, they should be removed as soon as possible once fertilisation has occurred.
'With our results we were able to demonstrate that amyloid fibrils, which were hitherto merely known as triggers of disease, can also perform important biological functions,' emphasises Professor Warner C. Greene and refers in this context to diseases like Alzheimer's and Parkinson's disease or so-called amyloid diseases. The Director of the Gladstone Institute for Virology and Immunology at the University of California San Francisco (UCSF) leads the scientific study together with Professor Jan Münch from Ulm. 'Seeing that amyloid fibrils are naturally present in semen, we already suspected that they play a role in reproduction. This concrete result, however, still came as a surprise,' the scientists agree.
Future research about the human peptidome
The future research on the biochemical function of these special protein aggregates is embedded in the new Collaborative Research Centre SFB 1279 at Ulm University. The German Research Foundation (DFG) funds the SFB named `Exploiting the human peptidome for novel antimicrobial and anticancer agents´ with over 12 million euros. The duration of this joint project is four years to begin with. At its centre is the interdisciplinary research on peptides that are endogenous to the human body and their potential for the treatment of cancer and infectious diseases. The investigation of the natural function of these protein elements and their optimisation for therapeutic application is an important part of that. One aspect will be the clarification of the biological role and natural function of amyloid-building peptides. Speaker of the SFB 1279 is Professor Frank Kirchhoff, Director of the Institute of Molecular Virology of the Medical Faculty at Ulm University.
Roan NR, Sandi-Monroy N, Kohgadai N, Usmani SM, Hamil KG, Neidleman J, Montano M, Ständker L, Röcker A, Cavrois M, Rosen J, Marson K, Smith JF, Pilcher CD, Gagsteiger F, Sakk O, O'Rand M, Lishko PV, Kirchhoff F, Münch J, Greene WC: Semen amyloids participate in spermatozoa selection and clearance; in: eLife 27 June 2017; doi.org/10.7554/eLife.24888.002
Text and media contact: Andrea Weber-Tuckermann
Translation: Daniela Wittmeier