Sperm Adventures in 3D

(October 16th, 2015) For decades, scientists have tried to understand how sperm manage to undertake the journey towards the female egg. Now, for the first time, a research group in Bonn followed these male cells in three-dimensional space providing new insights about their navigation strategies.





Looking for a mate is a big deal in the animal kingdom where the majority of species reproduce sexually. Individuals use different strategies to find a potential partner. Some may respond to mating calls from the opposite sex, like frogs and sloths. Others to beautiful coloured, visual stimuli, enchanting dances or wide hip-waist ratios, like birds, insects, and humans (respectively!). And yet others are guided by the smell of pheromones (lizards) or the taste of urine (giraffes) to find out whether the female prospect is ready to mate.

Interestingly, similar search-and-find strategies happen during fertilization. With the help of signals, the sperm cell has to find its way towards its final destination. The female egg releases molecules that act as chemo-attractants. They bind to receptors on the surface of the sperm flagellum and start a signalling cascade inside it. This allows the sperm cell to control its swimming behaviour and navigate, guided by this chemical gradient, purposefully towards the egg.

This journey has fascinated scientists for more than a century. However, it has only been studied by looking at the response of the male cells to the chemical gradient in a quasi-two-dimensional (2D) environment by keeping the cells within the focal plane of the microscope. A team of scientists led by the Department of Molecular Sensory Systems from Caesar (Center of Advanced European Studies and Research) in Bonn, Germany, has now been able to develop the techniques necessary to study this journey in three dimensions (3D).

Luis Alvarez and Jan Jikeli, two of the study’s leaders, explain that there were many motivations to move from 2D to 3D: “First, we wanted to confirm that things discovered in 2D are also replicated in 3D. This is not obvious because in 2D experiments cells are confined to a surface and there is friction between the sperm and the walls of the recording chamber that may affect the swimming behaviour.” The two were indeed able to confirm a finding that was previously hypothesised in 2D studies where sperm swim in circles: sperm navigate along helical paths, bending in a deterministic manner towards the attractant gradient.

What does this mean? To find the egg, sperm could use two different approaches: One hypothesis states that they randomly test different directions until they encounter the highest level of the gradient – this is where the egg waits. Alternatively, they could move in a deterministic way, meaning that they “know” which direction to follow before steering their path. For the first time, Jikeli, Alvarez, and colleagues have found evidence to support the second: the deterministic strategy.

And why is helical swimming important for sperm navigation? “Because it has a periodic component, always coming back and forth. This helps to evaluate where the egg is,” explains Alvarez, who also compares this behaviour to a scenario where one might be looking for food guided by its odour. One would move around and take a sniff at different positions, until finding it.

But the study not only confirmed what was previously predicted from 2D data, it also showed that sperm cells display different swimming behaviour when they lose the target. Jikeli et al. found that when sperm deviates from the correct path, it performs very abrupt “emergency turns” to swim back to the top of the gradient. “This had never been reported before, it is a very new feature that tells us that sperm cells are really versatile and that they are able to move, following some complex processing that depends on the chemical stimulation. If they miss the egg, they can try again,” adds Alvarez.

A combination of two powerful techniques forms the basis of this successful work: holographic microscopy and optochemistry. Jikeli explains that the former is based on the idea of having a coherent light source with a defined frequency, illuminating a sample. Fractions of the light will be scattered by the sample and will interfere with the non-scattered light to produce an interference pattern that is recorded by a camera. This interference pattern, analysed with complex algorithms, will give the location of the sperm cells away, in 3D. Jikeli affirms that although it has been around for half a century and is very cheap, this technology has not yet been widely used for investigating biological questions. They combined this method with optochemical techniques: using a photosensitive caged form of the respective chemoattractant, light created the 3D gradient that the sperm usually encounters.

Both methods together can be helpful to study many other questions, but in the short-term, the team wants to focus on getting a better understanding of the complexities of sperm navigation. After this first attempt with sea urchin cells, a well-established model for sperm chemotaxis, Alvarez and Jikeli mention that they would like to explore navigation of sperm in other animal species, maybe soon with mice sperm and potentially later with humans. Both agree that these techniques offer promising and exciting possibilities.

Alejandra Manjarrez

Images: René Pascal (Leeuwenhoek), Luis Alvarez (LabTimes)




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