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Aw nuts

The brain and balls overlap in over 13,000 ways

Scientists publish an “exhaustive comparison between brain and testis.”

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Riddle me this: Both of these organs guard their contents closely, appear wrinkly on the outside, and can determine the course of an individual life. What are they?

We’re talking about the brain and the testicles.

A review paper published Wednesday in Open Biology makes the case for this curious comparison, laying out the biological similarities between balls and brains. What they have in common, researchers argue, may help us understand conditions that affect both and find better ways to treat them.

“What we brought new to the topic was an exhaustive comparison between brain and testis, taking into account different perspectives,” Margarida Fardilha tells Inverse. Fardilha is the senior author of the review and an assistant professor in the Institute of Biomedicine-iBiMED at the University of Aveiro in Portugal.

Here’s the background — Researchers are finding mounting evidence suggesting brains are more similar to testicles than previously thought.

Previously, it was understood that they shared certain cellular similarities — specialized support cells, for example, called astrocytes in the brain and Sertoli cells in the testes. They both also have boundaries that allow certain materials in and block others out: the blood-brain barrier and the blood-testis barrier.

Brains and testes also, it turns out, have the highest number of genes in common of all the organs.

“... surprisingly, human brain and testes have the highest number of common proteins, compared to other human body tissues.”

This could have to do, Fardilha and colleagues explain, with both organ’s roles in distinguishing humans from Earth’s other creatures. This process is called speciation. The large brains we evolved with are, of course, what sets us apart as a species — but the uniqueness of our brain isn’t all that’s different.

“Sperm are the motor for speciation,” the authors write. This because sperm are thought to be a hub for the development of new genes. New genes can hasten the process of evolution because they can encode the instructions for new molecules.

Sperm are also the gatekeepers of the human species, so to speak, making it so we can’t reproduce with other animals. Brain and testes both have outsized roles, the review argues, in ensuring the evolution, and integrity, of humanity.

How they did it — Without knowing about their roles, it might be reasonable to assume that other organs of the body have just as much in common as brains and testes. After all, cells have similar basic structures and the tissues of our body are generally made up of materials that resemble one another.

But the review authors say the brain and testes have more in common on a minute biological level than other parts of the body, writing that the “analysis revealed that, surprisingly, human brain and testes have the highest number of common proteins, compared to other human body tissues.”

Scientists determined this unusual similarity by using a tool called the Human Protein Atlas to identify:

  • All the proteins created by the brain
  • All the proteins created by the testes

Using another computer program, they then compared them to all the proteins created by 28 other human tissues of the body. The goal was to see where the proteins overlapped.

They did the same thing using slightly different references for sperm cells and neurons, the primary cells of the brain.

Proteins are helpful when identifying and classifying different parts of the body because they are the products of DNA and RNA and can break down into and interact with other chemicals responsible for controlling how the body responds to its environment. The proteins that a certain cell or even a group of cells (a tissue like the heart or lungs) creates distinguishes it from others.

What was discovered — The researchers found in their comparison between the brain and testes that the two were unusually similar, more than the 28 other tissues of the body they evaluated. The brain and testes have 13,442 proteins in common, out of the 14,315 and 15,687 they each create.

“The brain and testes share 13,442 proteins in common.”

In their zoomed-in comparison of the primary cells associated with the brain and testes, the review team found that sperm and neurons also overlapped significantly, if not as dramatically. Of the 6,653 proteins that a sperm cell creates, a neuron also makes 5,048 of them. (Overall, a neuron creates over 13,000 proteins.)

The researchers then looked more closely at the proteins that were the most “highly expressed,” in these tissues and what processes they were related to. While it’s known the brain sends many of the signals that allow sperm to develop in the testes, more recently scientists have found that many of the proteins share roles that are related to brain development — and only a small percentage with sperm development.

The proteins that neurons and sperm shared, for their part, both had to do largely with cell and tissue development, as well as a process called exocytosis. This is when a cell expels materials transported in membrane-wrapped packages into the environment around it.

The overlapping proteins were also involved in cell signaling, a term that describes how cells communicate with one another.

A Venn diagram of the range of proteins the brain makes and the testes make, with the proteins they have in common.Open Biology / Matos, et al.

Why it matters — This striking resemblance between the upper and lower packages, the review authors reasoned, had to have a purpose. If they had similar biological functions, maybe it could explain links between conditions that harm both.

As it turns out, there is overlap in a few disorders that affect both brain and testes. For example, multiple sclerosis and male infertility can overlap. Meanwhile, certain dysfunctions of the brain have been linked to changed testicles. Pelvic surgery, diabetes, spinal abnormalities, and spinal cord injury can also lead to male infertility, through erectile dysfunction or semen abnormalities.

Also, and perhaps more controversially, in 2009 scientists found a correlation (which doesn’t mean that one caused the other) between overall intelligence and measures of sperm, like count, concentration, and movement. They reasoned that what makes humans biologically “fit” in one area could also go hand in hand with another. In another study from 2013, researchers actually found a relationship between testes size and parenting behavior: bigger testes sizes were correlated with less nurturing-related brain activity in fathers.

What’s next— If testicles and brains have so much in common, acknowledging and analyzing their shared biology could help move forward treatments for these issues. Or, if there was a treatment that worked for one ailment, it could help guide scientific inquiry in treating the other.

This team argues for a more thorough analysis of the shared proteins and their functions, which they say could lead to a better understanding of the mechanisms underlying diseases and better treatments. And that’s something to go nuts for.

Abstract: Several strands of evidence indicate the presence of marked similarities between human brain and testis. Understanding these similarities and their implications has become a topic of interest among the scientific community. Indeed, an association of intelligence with some semen quality parameters has been reported and a relation between dysfunctions of the human brain and testis has also been evident. Numerous common molecular features are evident when these tissues are compared, which is reflected in the huge number of common proteins. At the functional level, human neurons and sperm share a number of characteristics, including the importance of the exocytotic process and the presence of similar receptors and signalling pathways. The common proteins are mainly involved in exocytosis, tissue development and neuron/brain-associated biological processes. With this analysis, we conclude that human brain and testis share several biochemical characteristics which, in addition to their involvement in the speciation process could, at least in part, be responsible for the expression of a huge number of common proteins. Nonetheless, this is an underexplored topic, and the connection between these tissues need to be clarified, which could help to understand the dysfunctions affecting brain and testis, as well as, to develop improved therapeutic strategies.
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