Researchers reveal why heat stress damages sperm

Biologists from the University of Oregon used the model organism Caenorhabditis elegans to identify molecular mechanisms that cause DNA damage in sperm and contribute to male infertility after exposure to heat.

In humans, the optimal temperature for sperm production is just below body temperature in a range of approximately 90 to 95 ° F. Human studies have shown that exposure to temperatures is only 1 ° C (1.8 ° F) above this normal range adversely affects male fertility, said Diana Libuda, a professor at the Institute of Biology and the Institute of Molecular Biology.

The phenomenon of heat-induced male infertility is well known and the effects of modern exposure to heat such as hot tubs, tight clothing, and excessive driving time have been extensively studied. The underlying mechanisms that damage sperm and affect fertilization are not fully understood.

“In both humans and C. elegans, relatively small increases in temperature are sufficient to reduce male fertility,” said Libuda.

An increase of 2 ° C (3.6 ° F) above normal in C. elegans, a type of roundworm, resulted in a 25-fold increase in DNA damage in sperm development compared to unexposed sperm. Eggs fertilized by these damaged sperm did not produce offspring.

This basic research discovery is described in an article published online October 15 in the journal Current biology by researchers in the Libuda UO laboratory. Postdoc Nicole A. Kurhanewicz is the lead author of the study.

The study provides scientists with a roadmap for mammalian and human studies to confirm whether these same mechanisms contribute to male infertility, said R. Scott Hawley, an expert in meiosis research who was not involved in the research.

Hawley, a member of the National Academy of Sciences and dean emeritus of the Graduate School of the Stowers Institute for Medical Research in Kansas City, Missouri, learned of preliminary results at an academic conference.

“I think this is a trademark because it shows an environmental effect that changes certain sequences of DNA and, presumably, the proteins that control their activity,” said Hawley. “What Diana and Nicole have done is to clearly state what goes wrong at the molecular level when heat changes sperm formation, at least in worms.”

The paper also helps understand how meiosis, the process that produces sex cells, differs between sperm and eggs.

Sperm, the smallest cell in the human body, form billions of times at temperatures below body temperature and are produced throughout the life of the adult. Eggs, the largest cells in a human’s body, are formed internally where a constant temperature is maintained and are only produced for a limited time during the development of the fetus.

“We know that sperm development is very sensitive to elevated temperatures, while egg development is not affected,” said Kurhanewicz. “The data presented in this article suggest that the egg and sperm develop differently in different ways by the ability of mobile elements of DNA, also known as ‘jumping genes’ or transposons, to move around the genome, and how sensitively control them to heat stress, these mechanisms prevent this movement. ”

Transposons are segments of DNA that move and alter genetic information by inserting themselves in new positions. They also leave DNA damage behind. The movement of these “jumping genes” is normally suppressed during the development of sperm and eggs. However, this study found that transposons specifically move in the development of sperm upon exposure to heat.

The research team used microscopy to observe the development of sperm and eggs under both normal and heat-stressed conditions. In the latter case, the researchers saw higher levels of DNA damage in sperm, but not in eggs. Using next-generation genome sequencing, they also identified the positions of transposons throughout the genome, with and without exposure to heat.

“We found that after a heat shock certain transposons are found in new and more variable places in the male genome,” said Kurhanewicz.

The study, Hawley said, not only shows that a small increase in temperature affects the meiotic divisions, but it also identifies a mechanism – not just where the failure occurs, but what the failure is.

“It’s going to be exciting here,” he said. “If we can determine how big a change is, and if you are really concerned about environmental issues like hot tubs or boxers versus briefs, then with that molecular understanding we can reshape the debate for solid scientific reasons. “”

Chromosome defects due to excessive exchange of DNA in sperm and eggs

More information:
Nicole A. Kurhanewicz et al., Elevated Temperatures Cause Transposon-Associated DNA Damage in C. elegans Spermatocytes, Current biology (2020). DOI: 10.1016 / j.cub.2020.09.050

Provided by the University of Oregon