November 30, 2022

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'I find it cool, this simplicity in a sperm cell'

‘I find it cool, this simplicity in a sperm cell’

The sperm cell does not carry anything superfluous. In order to advance as fast as possible in the race to get to the egg first, the cell is completely stripped during its development. “Like packing a backpack for a long walk, you only take what’s absolutely necessary. I find it fascinating, that simplicity of a sperm cell,” says Zvija Ze’ev Ben Mordechai.

Ze’ev Ben Mordechai is Associate Professor at the Bigfoot Center for Biomolecular Research at Utrecht University. Using advanced microscopes, she examines the cellular structure of sperm cells from various mammals, and also close to humans.

What distinguishes sperm cells? “Well, people sometimes think there’s not much left to discover,” says Ze’ev Ben Mordehai. “Under an ordinary light microscope they really look like fairly simple cells, consisting of a head and a long tail. But with the super resolution of the microscope we use, you suddenly see the enormous complexity of the sperm cell.” “.

What makes microscopy a powerful tool?

“With cryo tomography, you can do a CT scan of the cell, as it were. The computer creates an image in which you can study the cross-sections of a frozen cell slice by slice, just as you can with a body CT. It is done in such detail that sometimes you can see individual proteins.

“Once you’ve done the scans, you first have to annotate all the structures on those black and white images: determine exactly which parts of the cell you see. You can then do 3D reconstructions of them in the computer so you know what the parts of the cell actually look like.”

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“The advantage over a conventional electron microscope is that you don’t have to preserve, cut or smear the sample; actions that can damage the structure, giving you a distorted image. What we see with cryo-EM is exactly how the parts sit in the cell.”

The sample is frozen in a microscope

Zfiya Ze’ev Ben Mordechai demonstrates how fast the freezing process can be. She fills an open thermos with liquid nitrogen, and in it a smaller metal container filled with liquid ethane. “Ethane has to be fast enough to freeze the formulation, with only nitrogen being too slow. It has to go so fast that ice crystals can’t form,” she explains.

The preparation is suspended over the liquid using tweezers. Then you depress the foot pedal, causing the tweezers to fall like a guillotine. Upon freezing, the sample is placed in a microscope where the shadow image of the electron beam can make the smallest details of the cell visible.

What did you discover?

“In reproductive medicine, it has long been a mystery where the second centrioles come from in a fertilized egg. Centrioles are parts of cells that are important for cell division. So you always need two; centrioles each attracting one half of the chromosomes. It was clear from previous research that the egg does not contain Centrioles, and until recently they have always been able to find only one centriole in a sperm cell.

“Through our microscopy, we’ve now seen what it’s all about. The second centriole looks very different than usual. Instead of the normal barrel-shaped rigid structure, this centriole looks like a bowl that can also move very smoothly. In a sperm cell it’s just below the head.” around the nucleus of the whiptail. We suspect it has a crucial secondary function in cell movement.”

This may sound crazy, but the egg is too big to study with microscopy

And what happens to this strange centriole after conception?

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“That’s a good question, we don’t really know yet. After fertilization you can still see the tail of the sperm in the egg for a while, and we’d like to see what’s going on in the cell. This might sound crazy, but the egg is too big to study with a microscope. You can’t freeze That cell is fast enough because of its size. We’re working on a solution, but we’re not there yet.”

Could this research also do something about male infertility?

“Yes, we hope to find something at a basic level that is hindering fertility. That is why we have now started a collaboration with the fertility clinic at UMC Utrecht. The IVF success rate is low, 25 percent in young women, and it gets worse in older women. This is a heavy burden for couples who They want to have children.

In the case of male infertility, the cause is unknown in two thirds of cases. Sometimes ICSI is still a solution in which the sperm is injected directly into the egg. Under the microscope, you can see non-motile or distorted sperm cells, but if you don’t know what’s wrong and you continue to do IVF, there is a risk that you will pass the defect on to the next generation undetected. We really need to understand this better.”

Conversely, you are also hoping to find a goal to prevent pregnancy in men. Is this realistic?

“I think so. If we understand better how it works, we can also disrupt it. Mobility is very important for sperm cells. But the moment it’s formed and stored in the epididymis, it can’t swim yet. If we figure out what’s essential to this maturation process, and our basic business, Others could start developing birth control pills for men.”

You were not allowed to enter the lab unless you tested for corona

How do you like it as a foreign researcher in the Netherlands?

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“Excellent! I love working internationally. It is no coincidence that my group of three PhD students and one postdoc includes a Dutchman, a Filipino, an Indian and a German. We speak English among ourselves. I love this cultural diversity because it always brings new ideas that complement each other. I am also a member On the Advisory Board of the College of Science in Diversity.

Is Corona still hindering the work of your department?

At one point, all laboratories had to close due to the closure measures against Corona. We were not allowed to do anything and had to stay at home. There was one exception: you were only allowed to enter the lab if you were researching for corona. Then several scientists changed their research to continue the work. I thought about it for a while, but I didn’t.

“We were fortunate to already have several of our measurements ready, all that remained was to work and write the results. This resulted in four beautiful publications last year – which is not bad in my opinion.”