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Spotting Chromosomal Abnormalities in Human Sperm

September 16, 2021
Riley Kleemeier

For a long time, there was no efficient way for doctors and scientists to evaluate the health of men’s sperm cells. Especially for men who have had to undergo any sort of chemotherapy or radiation treatment, there is very little information about how these drugs can cause chromosomal damage to human sperm. 

The research presented in this article focuses on men who have undergone chemotherapy or radiation and want to embark on the journey of having a family. As you will find in this article, the research is still new but has plenty of space to grow and expand over time.

Fluorescence In Situ Hybridization (FISH)

FISH is a newly developed analysis technique that examines sperm DNA for any evidence of chromosomal defects. This technique has been decades in the making, thanks to Andrew Wyrobek and his research team. 

The team included scientists from Lawrence Livermore National Laboratory, Stanford University, MD Anderson Cancer Center, and the National Autonomous University of Mexico. Wyrobek is a medical biophysicist at Berkeley lab, and his studies include the effects of radiation and man-made chemicals on breast cancer, brain function, and male reproductive health. 

Chromosomal abnormalities as a result of chemotherapy

Chemotherapy and other cancer treatments save lives, but they also cause extreme side effects for most patients. Most of these side effects are easily noticed, like nausea and hair loss, but there are other side effects that have not been extensively studied until now.

A patient undergoing chemotherapy.
A patient undergoing chemotherapy. This year in the U.S., it is estimated that 8,830 people will be diagnosed with Hodgkin lymphoma. Image courtesy of Cancer Today.

Research shows that chemotherapy treatments are genotoxic. This means that they can damage cancerous and noncancerous cells’ chromosomes, as well as mutate DNA. 

When these damages occur to germline cells — egg or sperm cells — they can cause fetal birth defects. These risks have been shown to diminish over time, but there is still much research to be done on how these drugs damage human sperm.

This is where FISH comes in. 

How FISH Works

FISH helps to identify where a gene falls within a chromosome. First, scientists prepare short sequences of DNA to match up with a portion of the gene they are looking for — they call these “probes.” These probes are then labelled with fluorescent dye. 

DNA is made up of two strands of molecules that bind to each other like “chemical magnets.” The probes bind to the strand of DNA. Then, researchers are able to locate the chromosome by looking for the fluorescent tag. 

When using the FISH method, scientists are actually able to probe the DNA for a variety of chromosomal defects all at the same time. This specific version of the FISH technique is called the AM8 sperm FISH protocol, developed by Wyrobek and his team.

Using FISH to detect chromosomal abnormalities

In patients undergoing chemotherapy or other genotoxic treatments, scientists can measure aneuploidy — the presence of one or more extra chromosomes, or the absence of one or more chromosomes — in sperm. Sperm that show these chromosomal abnormalities can fertilize an egg that may have severe health issues.

Wyrobek used trisomy 18 as an example of this, saying that fetuses with this condition typically die before birth or within a year of birth. Trisomy 18 occurs when there is an extra copy of chromosome 18, or a fetus with an otherwise unbalanced chromosomal rearrangement. 

But FISH can detect these chromosomal abnormalities before the egg is fertilized, preventing these conditions. They can also detect when the chromosomes are arranged in a balanced format — in other words, no genetic material is lost or gained. Balanced rearrangements can support a live birth. 


Image of a pregnant woman.
FISH can open the door for safer pregnancies. The technique can be used to help many families who have gone through the grueling steps of cancer treatment and would like to have children.

Results of the study

Wyrobek and his team studied the sperm of nine Hodgkin lymphoma patients. These patients were studied before, during, and after their cancer treatment regimens.

The results indicate that sperm produced by these nine patients during treatment had 10 times more chromosomal defects than sperm produced before treatment. Six months after their treatments, their sperm was studied again, and researchers found that their sperm had returned to “pre-treatment quality.” 

Wyrobek felt encouraged by these results, explaining that they are “a first step toward applying this method to any human situation — such as aging, illness, drugs, or exposure to environmental toxicants — to determine genetic risks to male germ cells…”

The results have potential in a wide variety of healthcare spaces and family planning purposes. 

Conclusion

Although this research could be life-changing for men who want to have children, the research is still very new. There is still more validation and development to be done before doctors can use this method in their offices. 

The FISH method is an important scientific discovery that could impact many areas of medicine. Undergoing treatment for cancer or any other illness doesn’t mean that the door for family planning should be closed, which is why Wyrobek believes so strongly in his research. 

FISH is a new way of visualizing DNA and genetic material in individual cells. Its application won’t end with chromosomal abnormalities of sperm. With this method, any number of chromosomal abnormalities or genetic mutations can be identified before they become a serious problem.


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