When sperm fall by the wayside

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Masters student Ines Ansmann appraises a high-res analysis of human sperm © WWU

Masters student Ines Ansmann appraises a high-res analysis of human sperm © WWU - MünsterView

In fairy tales, the king’s son usually has to solve three tasks in order to win the princess’s hand. This, however, is nothing compared to the challenges which await sperm on its way to the egg - or, increasingly, which spell failure. According to a number of studies and reports in the media, male fertility is in danger. In spite of this, there are only a few institutes which are investigating the genetic and molecular causes of sperm defects - but one of the most important institutes is in Münster.

The Center for Reproductive Medicine and Andrology (CeRA) is part of Münster University Hospital (UKM) and Münster University and focuses above all on translation, i.e. the transfer of research findings to practical applications. “We have a long tradition and nowadays we’re a kind of flagship,’ says Prof. Stefan Schlatt, who heads the Center. “What we’re concerned with are specific questions in the field of reproductive medicine and our patients’ desire to have children. This puts us among the leaders in Europe, possible even at the top worldwide.’

What is helpful in this respect is that CeRA is broadly based and has a good network of connections. These include not only the Institute of Reproductive and Regenerative Biology and the Department of Clinical and Operative Andrology, but also - in collaboration with UKM’s Gynaecological Clinic - the University Fertility Clinic. “A professorship in Reproductive Medicine will follow shortly,’ says Prof. Frank Tüttelmann, Director of the new, thematically closely associated Institute of Reproductive Genetics.

The interdisciplinary approach taken by medical specialists - collaborating with physicists, chemists, biologists and experts in computer-assisted processes - is necessary because sperm, once inside a woman’s body, have to complete a kind of decathlon, without any possibility of a second chance. The tasks the sperm have to solve are varied - as are the possible defects. First, they have to survive the unpleasantly sour vaginal environment and penetrate the mucus barrier of the cervix. This is followed by a long phase of swimming through the uterus and the fallopian tube.

Even when they have reached their destination, the sperm still have to present themselves to the eggs as a suitable, species-specific candidate and, with a final hyperactive effort, penetrate the embryonic membrane to reach the egg cell. This hard process of selection may seem exaggerated, but biologically it makes a great deal of sense - as a form of quality control. But what if ever fewer candidates are up to the job? Then the desire to have children remains unfulfilled - this male problem was once a taboo subject, but now it can no longer be ignored.

“We don’t need to worry that we might soon become extinct,’ says Prof. Timo Strünker, who is studying how sperm orient themselves and find the route they have to take. “The world’s population is continuing to grow steadily.’ Nevertheless, he adds, there is still concern about fertility because the numbers and quality of sperm in men in the Western world is declining. “And that’s something we naturally have to investigate,’ he says.

Because the formation and function of sperm are so complex, there cannot be any quick answers or easy solutions. A number of possible causes of the sperm crisis are still being discussed - for example, environmental factors which cause disruption to the hormone system. Independently of the apparent sperm crisis, there is another critical factor: age. Couples’ fertility declines as the years pass. In spite of this, people in the West, especially, are having their first child ever later in life.

Or they try to, at any rate. If the desire to have children doesn’t meet with success, and the woman’s fertility appears to be intact, the men often come to Münster in a search for answers and for help. In such cases, a few examinations are necessary. Are there enough sperm? Are they well-formed? Can they move properly? If there is a problem, the sperm experts can often establish this when they take a look through the microscope.

Other functions have to be measured. What may then be seen is that the sperm tail is a tad too weak, too slow or beats irregularly. It might be that there is a malfunction in the sensor which helps the sperm to localise the egg by means of a certain hormone. Timo Strünker’s team has decoded it in detail - which took years to do. This was because if sperm have a basic similarity to other cell types, they will have developed their own variations for many cell components.

This means that the findings from other areas, and the methods used there, can only be transferred and applied to sperm to a limited extent - which is something which often delays any increase in knowledge. But even if a defect is known and, in specific cases, has been shown to exist, the question of how the malformation arose often has to remain unanswered. The answer is to be found in the genetic material of the sperm’s progenitor cells. Which mutation in the hereditary molecule DNA is preventing the sperm from maturing in sufficient numbers and being capable of functioning properly?

These are the questions which Frank Tüttelmann and his team are investigating. “Our overriding aim is to be able to give more men a genetic diagnosis. In other words, to be able to explain to them why they are infertile,’ he says. Ultimately, the aim is for all research findings to lead to individual diagnoses and tailor-made treatments for patients, thus closing the gap between research and practice. This is a long journey, but Münster is well equipped for the task.

First Institute for Reproductive Genetics

For a long time now, the University of Münster has been a unique location in Europe for research into fertility. The clinical research group “Male Germ Cells: from Genes to Function’, set up in 2016, has been making an important contribution to this. The group is headed by Frank Tüttelmann, the only Professor of Reproducive Genetics in Germany so far. The group’s overriding aim is to decode the genetic causes of male infertility in order to be able to make precise diagnoses and improve treatment for the men affected.

The multidisciplinary approach taken by the group, closely linked with hospital and research, received recognition this year: the German Research Foundation (DFG) approved a continuation of funding, and in September there followed the establishment of Germany’s first Institute of Reproductive Genetics. The researchers are quite certain that these are important steps on the way to getting to the bottom of the genetic causes of infertility. At any rate, Frank Tüttelmann is optimistic: “We’re certain that the coming years will bring a lot of new findings in research into reproductive genetics.’

Susanne Wedlich

This article first appeared in the University newspaper wissen

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