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Male Infertility: New Cause Found?

A study done recently finds a new potential, natural cause of male infertility. This discovery marks a deeper understanding of biology, and therefore may lead to additional discoveries being made down the road.

February 5, 2021
Charlotte Pearse

Scientists think they may have just found another reason for male infertility, and they’re excited about what it could mean for the future.

In order to find ways to assist those who struggle with infertility, it’s important to know more about the reason behind its occurrence. An issue cannot be solved without first knowing as much as you can about the problem.

More and more research is being poured into the subject every day, and now there are a lot of options for people who want to have children to consider apart from natural conception, such as IVF, adoption, surrogates, and depositories.

IVF is one of the most popular options for women who have trouble conceiving, but male infertility can also be an obstacle that couples face, and  options differ based on where the issue lies. Female infertility is slightly more common, but only 2% more so.

Infertility is something that a lot of men struggle with too, and just as much effort goes into aiding with this as it does for women. Especially today, with the emphasis placed on medical health and study, it’s very important to keep up to date with the research that is going on. This is particularly important for people who are considering starting a family.

A study was done recently that found a new possible explanation for male infertility, relating to the flagellum of the sperm.

Background of the study

The tail of a sperm tail is called the flagella, and it contains microtubules. Microtubules are formed by a protein called tubulin, and serve a variety of functions. 

One specific modification of tubulin, called glycylation, is what keeps sperm swimming in a straight line. What does this mean for infertility, though?

The flagella’s motion— which must be very precise —is essential to the ability of the spermatozoids to swim, which is in turn essential for the sperm to reach the egg. Therefore, a lack of this enzyme and the subsequent lack of movement caused by it can lead to infertility.

An image of a pomegranate on a white backdrop, with almonds placed in front of it. Black lines have been drawn behind the almonds to make them look like sperm cells.
The journey that a single sperm cell must successfully make to reach and fertilize the egg is hardly as simple as this representative photograph using a pomegranate and some almonds. The slightest imperfect condition can render the sperm incapable of its duty.

Scientists from a variety of different institutions looked into why this is the case, and how exactly glycylation affects sperm movement. The involved organizations are the following:

  • The Institut Curie, Paris
  • The Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Dresden 
  • The Center of Advanced European Studies And Research (CAESAR), Bonn
  • The University of Bonn
  • The Institut Cochin, Paris
  • The Human Technopole, Milan

Research

There are two enzymes that contribute to the glycylation of mammals, and so scientists generated mice that lacked both to investigate how the lack of glycylation would impact the function of sperm.

They found that despite this lack of essential enzymes, they could not observe any significant negative impact at the organism and tissue levels. 

The assembly of the flagella was unchanged, and the sperm cells were able to swim, though they were subfertile. This means that natural conception is possible, but takes longer to occur.

Further analyses were conducted with computers and cryo-electron microscopy,  which allowed scientists to look at the molecular structure of the samples used. 

A close up image of a microscope's lenses.
Microscopes are one of the most important advancements made in science and technology to this day, allowing researchers to see what we never could with only the naked eye. In this particular study, no significant differences were noted until the use of one.

It was revealed that though the flagella had no problem with structure, the mutated enzymes prevented the motors that powered the flagellum’s beating from coordinating.

The affected sperm would swim in circular paths, which is incredibly unusual in mammals. This altered path makes it more difficult for the sperm to reach the egg for fertilization.

In fact, humans are more sensitive to a lack of sperm mobility, so fertility in human males would likely be impacted more severely than the mice used in the study.

One of the coordinators of the study, postdoctoral fellow at the Institut Curie Carsten Janke, stated that “We observed functional defects on sperm from mice lacking glycylation, which resulted in a reduction of fertility. Since mice as a model system are known to have robust fertility, a similar defect in humans, could lead to male sterility.”

Significance

So, why is this study so important?

Not only does it give us more information about what can cause male infertility, it also provides further avenues of study by proving the significance of microtubules and how they can greatly impact protein production in cells.

As stated by two of coordinating authors in the study, Gaia Pigino and Luis Alvarez, “Since sperm flagella are one of many types of cilia in our bodies, we expect similar tubulin modifications to be important in various cilia-related functions. Hence, our work opens a door to a deeper understanding of multiple diseases, such as developmental disorders, cancer, kidney diseases, or respiratory and vision disorders.”

An image of a man in a lab coat and goggles looking at a computer.
Computers were a part of the stage of this study that finally provided the answers researchers were looking for. More research methods of the same kind may be employed in the future on similar hypotheses, such as the many other functions of cilia and the way they could be impacted by a similar problem, as detailed in the quote above.

The results of this study point to related discoveries elsewhere in the medical field that have yet to be made, pertaining to many other aspects of human health besides fertility. As the above quote points out, the functions of cilia hardly apply to just sperm cells.

However, only time will tell if more will be found as a result of this research.

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