Cells in the human body have very different life spans, depending on their type and function. Skin cells renew themselves every two to four weeks. Liver cells can last up to 500 days. Egg cells are particularly long-lived: they are created in the female body even before birth and do not renew themselves. Thus, a 30-year-old woman has egg cells that are just as old.
The egg cell-s ability to repair damage in its DNA is crucial to ensure that it remains functional for a long time and does not die. To this end, egg cells have developed a complex repair machinery with different repair pathways. In all these pathways, special proteins detect changes in the DNA and repair them. This machinery is also responsible for repairing DNA damage that occurs in the father-s sperm and in the developing embryo. Despite the presence of multiple DNA repair mechanisms, unrepaired DNA damage accumulates in aging egg cells. Until now, it has been unclear why this happens.
Less efficient and error-prone repair
A research team led by Max Planck director Melina Schuh, head of the Department of Meiosis at the MPI for Multidisciplinary Sciences, has now compared young and aging egg cells in terms of their DNA damage and DNA repair machinery. Using high-resolution fluorescence microscopy, her team determined the amount of DNA damage in human and mouse egg cells of different ages, mapped important repair proteins in the cell nucleus, and analyzed how their activity and interactions change with age. -We found that DNA repair slows down in aged oocytes,- says Schuh. -As a result, DNA damage accumulates in the cell.-In addition to these changes, the researchers identified another reason for increased damage in aged egg cells: The amount of the protein cohesin decreases with increasing maternal age, leading to chromosome segregation errors. Cohesin holds sister chromosomes together until they are ready to separate during cell division. At the same time, the protein is essential for DNA repair: If a strand of DNA is broken, for example, it ensures that the damaged part can be repaired using an intact DNA strand as a blueprint.
But it is not only aging egg cells that are affected by cohesion loss. -Interestingly, reduced cohesion also led to higher levels of DNA damage and slower DNA repair in young egg cells,- reports Schuh. -Apparently, it is not only the slower, more error-prone repair machinery but also the decline in cohesin with age that promotes accumulation of DNA damage and death of aged egg cells.-
Changes in DNA repair compartments and cohesin loss promote DNA damage accumulation in aged oocytes
Egg and sperm cells are highly sensitive during their development. When, for example, there is an error in the way the genetic material is divided between the individual gametes, the resulting embryo will often either be nonviable or suffer from severe birth defects. Melina Schuh from the Max Planck Institute for Biophysical Chemistry in Göttingen wants to find out why egg maturation is so error-prone. The results of her research could one day help couples who are unable to have children.
A Göttingen research team has succeeded in visualizing the entire process of ovulation in mouse follicles in real time for the first time. The new live imaging technique allows to study ovulation with high spatial and temporal resolution and opens up new possibilities in fertility research.
In Germany, animal research is primarily carried out in the areas of basic research, medicine and veterinary medicine. Animal research can also be required to identify factors that pose a risk to the environment. The toxicity of chemicals is also investigated using animal research. It is a legal requirement that all’active substances are tested in animal experiments for effectiveness and side effects.
