Losing your Y chromosome could have dramatic health consequences: ScienceAlert

Bladder cancer cells with a missing Y chromosome are better primed to evade our immune system, according to a new study using mice and led by researchers at Cedars-Sinai Medical Center and Ohio State University in the US .

This discovery partly explains why so many cases of specific cancers contain cells that no longer have a male sex chromosome and potentially why men are statistically more prone to cancer.

Like hair color, skin elasticity, memory and eyesight, the Y chromosome has a habit of disappearing with age, left behind while the rest of our genetic library is copied and transferred into a new fresh cell.

For the most part, it seems like we’re doing relatively well without it, at least for a while. Compared to the 156,000 base pairs that make up the X chromosome, the small swath of DNA that triggers male sex characteristics only contains 57,000 base pairs of information, coding for various genes that don’t seem too life-critical.

Still, it’s clear that something in these sequences must make a difference when it comes to overall health. For example, the loss of the chromosome in blood cell-producing tissues is bad news for heart function. Somewhere between 10 and 40 percent of bladder cancers also contain cells that lack a Y chromosome, suggesting hidden protective functions.

To find them, Cedars-Sinai urologist Dan Theodorescu led a team of scientists in an investigation of bladder cancer prognosis in mouse models, validating the findings with an analysis of single cells taken from bladder cancers. the human bladder.

Cells from mice that had naturally lost their Y chromosome or removed it through CRISPR-Cas 9 gene editing grew more or less the same as cells with the sex chromosome when observed in vitro.

Inside the mice, the distinction became much more apparent. Cancers without a Y chromosome have become much more aggressive, growing at almost twice the rate of their genomically complete versions.

The disruption of key immune genes in the Y-positive mice again equalized growth rates, implying that something in the chromosome facilitated the body’s anti-tumor adaptive immunity. Further analysis confirmed that two specific genes – KDM5D and UTY – were primarily responsible for the additional protection.

An analysis of the proteins produced by mouse cancer cells and the comparison of the critical immune cells present in the two different tumor types shed light on the picture, suggesting that cancer-fighting T-cells were rapidly exhausted in their attack on cancer cells. cells without genes.

Sifting through databases of proteins active in human bladder cancers supported findings from mouse models, claiming that the presence of a Y chromosome in bladder cells produces important proteins that help the system immune system to attack the growing tumor.

Not only does this give medical specialists something to look for in determining the aggressiveness of bladder cancers, but other experiments have also shown that Y-negative tumors respond well to a type of cancer treatment known as immune checkpoint inhibitor.

If you’re inspired to give your Y chromosomes a big hug and tell them you’ll never let them go, you might want to wait.

Another recently published investigation by researchers at the University of Texas in the United States assessed gender differences in colorectal cancer in mice, finding differences similar to those measured in humans.

An analysis of a known mutation has revealed that it regulates a gene on the Y chromosome that is primarily responsible for giving tumors a head start in migrating around the mouse body. This Y-chromosome gene happens to be KDM5D, one of the specific genes identified as protective in bladder cancer.

Depending on the type of tissue, this little “pamphlet” of a chromosome could be a weapon against cancer or a practical manual for a tumor to take to the sea and invade new organs. It just depends on which disease you prefer to be most at risk of.

With studies suggesting the Y chromosome may be dying out as an evolutionary mode, it’s hard to know whether we should rejoice or lament.

These studies were published in Nature here and here.

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