A new interplay between the reproductive germline and the body

When the DNA of germ cells is damaged, the production of offspring must be delayed until the genetic material is repaired. By studying the nematode worm model Caenorhabditis elegans, the researchers found that to gain more time to repair their DNA, germ cells activate the innate immune system that then triggers enhanced endurance of other body tissues.

Now, for the first time, it is clear how germ cells can influence the reproductive lifespan of the body when they require more time to guarantee accurate passage of the genetic material to the next generation. Moreover, the new insights might lead to a better understanding how the immune system mediates systemic responses to DNA damage, a process that plays an important role in the natural defense against cancer.

From generation to generation, the genetic material needs to be transmitted through the germline, where germ cells produce sperm and egg cells. The maintenance of the genome in germ cells is thus a prerequisite for the survival of the species. While germ cells continue their lives endlessly as they carry the genetic information to future generations, the somatic tissues (all non-reproductive cells of the body) function as their ever-ageing carriers. But how does the whole organism respond when the genome of germ cells is damaged thus preventing them from generating offspring?

In the current issue of Nature, Björn Schumacher’s group at the Excellence Cluster for Ageing Research at the University of Cologne reports a novel type of interplay between the germline and the somatic tissues. Strikingly, they found that the immune system alerts the body when germ cells are damaged. The scientists revealed that when the genome of germ cells is damaged, somatic tissues respond by elevated resistance to various stress factors. The increased stress resistance makes the somatic tissues more durable and enables the body to survive the stress longer, thus “buying” time to postpone progeny production until the germ cells have repaired their DNA.

The Cologne biologists identified the novel influence of the germline on somatic tissues by studying the simple nematode worm Caenorhabditis elegans. The worm is widely used as important model system because many biological processes that are relevant to human health are also present. Germ cells halt their activity when their genomes are damaged, thus halting offspring production. Schumacher’s team observed that the damaged germ cells produce innate immune factors that are normally secreted in the intestine when the worms have ingested pathogens. Indeed, the innate immune response to DNA damage in the germ cells made the worms more resistant to pathogen infection. In addition, the somatic tissues became highly durable even under environmental stress conditions. Furthermore, in the somatic tissues, the innate immune response led to elevated quality control of proteins, which contributed to this increased stress resistance. The scientists named this new phenomenon “germline DNA damage-induced systemic stress resistance” (GDISR).

The activation of innate immune responses to DNA damage is relevant for fighting cancer cells in humans. DNA damage in somatic human cells can lead to mutations that can transform cells into cancer cells. The human immune system reacts to the damaged cells in the body by eliminating them; however, some cancer cells acquire mutations that allow them to disguise themselves from the immune system and continue to grow. The new results from the Schumacher group provide a basis for the investigation of innate immune responses to DNA damage in a very simple biological system. These mechanisms might then enable the development of therapies that activate the immune system to effectively eliminate cancer cells.

It will be particularly interesting to investigate how the human body responds when the germ cells’ genomes are compromised. The foundation is now laid for better understanding how the human body responds to DNA damage in germ cells and how the reproductive capacity might be prolonged when germ cells require time to repair their genome.