Seeing the bigger picture of fertility

Seeing the bigger picture of fertility

Having babies isn’t always easy. Around one in six couples in Europe experiences infertility, and as well as the emotional burden, many spend substantial amounts of money on fertility treatments. We also depend on fertility for our food and economic growth: in agriculture, equine and breeding industries, the ability of animals to reproduce healthily is key to success.

Understanding reproduction across the animal kingdom is key to improving how we manage fertility in humans, according to Professor Sabine Koelle, Professor of Anatomy and Developmental Biology at UCD School of Medicine, who is trained both in human and veterinary medicine.

By examining the basic principles of reproduction, she is overturning accepted norms about how sperm, egss and the female genital tract operate and she is opening up new approaches to treating infertility. 

Variations offer clues

Human doctors and veterinarians can learn a lot from each other when it comes to reproduction and fertility, says Professor Koelle. “If you know what variations are possible across animal species, that can help us to develop new ways of diagnosing and treating problems in humans,” she says. “But the problem is that human doctors and vets don’t really cross over and communicate with other, and medical students only learn about the one species, the human. The One Health approach looks to bring the human and animal research together for that better understanding.”

Many aspects of reproduction are similar across humans and other species, she notes, but there are important variations that give us plenty of insights. “It’s like a cake. We have the basic recipe of the body of the cake, and these are the shared functions across species. But then there are differences between species, and these are like different icings on the cake, and this is where we can get clues about what is possible for reproductive technology.”

She offers some examples: human sperm survive in the female for about 3-4 days, so how might we find out how to increase their survival time if needed?

“If we look to other animal species, some female bats can store sperm for several months and they still function, and there is a snake in Australia where sperm can survive for nine years,” says Professor Koelle. “We can learn a lot from them about the possibilities of keeping sperm happy for longer. 

In female humans, when an egg gets released from the ovary, it typically survives for about 24 hours – could we extend that period? “In horses, an egg can survive for several reproductive cycles,” says Professor Koelle. “From this we know there must be signals that keep eggs alive longer than 24 hours.”

Seeing the bigger picture

Professor Koelle works with colleagues in Europe, the US and Australia to look at reproduction in humans, cows and mice among other species, both in females and males.

The breadth of her approach allows her to compare species and develop a bigger picture. Indeed, pictures are central to her approach, because she has established novel imaging technologies for visualising the living reproductive tract in order to see how it works and how we might treat disease or infertility.

One of her favourite regions to explore is the oviduct, a tube that conveys the egg from the ovary towards the uterus. “It is very well hidden in the abdomen and not easy to get an image of it, and people just assumed that it was this tube and the egg moves along it,” she explains. “But we are finding it does so much more. Using digital videomicroscopy and probe-based confocal laser endomicroscopy, Professor Koelle and colleagues have captured mesmerising movies and images of an egg as it journeys along the oviduct in humans. Their findings are challenging the perception of the oviduct as an inert tube

“We have found that the oviduct is pulling the strings, it basically operates as quality control, signalling to the egg, and if that egg is up to standard then it nourishes the egg. It also nourishes the sperm and gives them the decisive signal to hurry to the oocyte after ovulation. If the egg is fertilised in the oviduct, this is the first point of communication between the mother and the embryo. The embryo signals ‘hello I am here’ and if there is no response from the oviduct, there is no pregnancy.”

Scarring, infection or blockage of the oviduct can be a root cause of infertility, but according to Professor Koelle it is often undiagnosed because the site is so difficult to routinely image. “In cases where you have ‘idiopathic’ infertility, which means we can’t say what is not working, I often suggest that we flush the uterine tubes, and this might solve the problem.

Understanding the behaviours and characteristics of functional sperm is important for diagnosing issues in male fertility, she explains. “Often in fertility assessment, human sperm are judged on how they look and move, but we are seeing there is more to it, even the sperm that looks a bit ugly in the dish can be the one that functions well.”

Future fertility

Professor Koelle and colleagues are currently focusing on how ageing, medications and hormone treatments can have an impact on fertility in humans and other species, and they are already uncovering the negative effects of some painkillers on the process. “These and other medications are used widely, we need to know which are the silent effects on the reproductive system,” she says.

Meanwhile, she is spreading the word at conferences about the need for human and veterinary medicine to work together more closely and she is broadening the perspective of a new generation of doctors. “I am teaching undergraduate and postgraduate medical students in UCD about what happens in other species, not just humans,” she says. “They can now see how necessary it is to look up research on cows, sheep, pigs and mice as well as humans