Oregon scientists uncover sub-atomic instruments that produce DNA harm in sperm

Overview

• Post By : Kumar Jeetendra


• Source: University of Oregon


• Date: 25 Oct,2020

University of Oregon biologists have used the model organism Caenorhabditis elegans to identify molecular mechanisms that produce DNA damage in sperm and contribute to male infertility following exposure to heat.

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

The phenomenon of heat-induced male infertility is well understood, and the effects of modern exposures to heat such as hot tubs, tight clothing and excess drive times have been extensively studied. The underlying mechanisms that damage sperm and impair fertilization aren’t completely understood.

An increase of 2 C (3.6 F) above normal in C. elegans, a type of roundworm, led to a 25-fold increase in DNA damage in developing sperm compared to unexposed sperm. Eggs fertilized by those damaged sperm failed to produce offspring.

This basic research discovery is detailed in a paper published online Oct. 15 in the journal Current Biology by investigators in Libuda’s UO lab.

The study provides a roadmap for scientists to pursue studies in mammals and people to confirm if the very same mechanisms contribute to male infertility, said R. Scott Hawley, a meiosis research expert who was not involved in the study.

Hawley, a part of the National Academy of Sciences and dean emeritus of the graduate faculty of the Stowers Institute for Medical Research in Kansas City, Missouri, had heard about preliminary findings in an academic conference.

“I think this is a hallmark paper as it shows an environmental impact which alters specific DNA sequences and the presumably the proteins that control their activity,” Hawley said. “What Diana and Nicole’s work has done is to clearly state what goes wrong, at the level of molecules, when sperm-making is changed by heat, at least in worms.”

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

Sperm, the smallest cell in a person’s body, form by the billions in temperatures below body temperature and are produced through the entire adult lifespan. Eggs, the largest cells in a person’s body, are formed internally, where a consistent temperature is maintained, and are produced only for a limited time during fetal development.

“We all know that sperm development is very sensitive to increased temperature, while egg development isn’t affected,” Kurhanewicz said. “The information presented in this paper suggest that another way sperm and egg develop differently is in how closely they control the capability of mobile DNA elements, which are also called’jumping genes’ or transposons, to move from the genome, and how sensitive to heat stress those mechanisms are in preventing that movement.”

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

Diana Libuda, Professor, Department of Biology and Institute of Molecular Biology

They also leave DNA damage in their wake. Movement of these”jumping genes” is normally repressed in developing eggs and sperm. But this study found that with exposure to heat transposons are moving specifically in developing sperm.

The research team used microscopy to observe developing sperm and eggs under both normal and heat-stressed problems. In the latter, the researchers found higher amounts of DNA damage in sperm, but not eggs. Using next-generation genome sequencing, they also identified the areas of transposons across the whole genome with and without exposure to heat.

“We discovered that following heat shock, certain transposons are located in fresh and more variable locations in the male genome,” Kurhanewicz said.

The analysis, Hawley said, not only indicates that a small rise in temperature affects meiotic divisions but she also identifies a mechanism – not just where the error occurs but what the error is.

“If we can determine how much of a change is bad, and if you are really concerned about the ecological matters like hot tubs or’boxers versus briefs’, this kind molecular understanding may enable us to reframe the debate on solid scientific grounds.”