Healthy eggs: Long-lasting proteins as a key? | N6974

Extremely long-lasting proteins in the ovary could help keep egg cells healthy and preserve fertility for a long time. In the mouse egg cell shown here, the chromosomes are colored magenta and the cytoskeletal protein actin is colored blue and white.
(c) Melina Schuh / Max Planck Institute for Multidisciplinary Sciences
Female mammals, including humans, are born with all of their eggs. Of the approximately one to two million eggs a woman has, around 400 mature by the time she reaches menopause and can be fertilized. Some of the eggs therefore live for several decades – and must remain functional over this long period of time. Extremely long-lived proteins in the ovary could play an important role in this, as research teams from Göttingen have now discovered in experiments with mice. These long-lived proteins apparently help to preserve fertility for as long as possible.

«Egg cells must be preserved throughout a woman’s fertility phase so that healthy embryos can develop from them,» explains Melina Schuh, director at the Max Planck Institute (MPI) for Multidisciplinary Sciences. Even in mice, which can only reproduce for a little over a year, the lifespan of egg cells is much longer than the average lifespan of proteins. Living cells recycle most of their proteins within just a few days. However, depending on the cell type and function, not all proteins are broken down at the same rate.

Many extremely long-lasting proteins in the ovary

Together with teams led by group leaders Juliane Liepe and Henning Urlaub, Schuh’s team has now quantitatively investigated how frequently particularly long-lived proteins occur in ovaries. For their experiments, the researchers combined various biochemical and molecular biological methods with mathematical modeling. «This multidisciplinary approach enabled us to observe proteins in ovaries and egg cells of mice at different ages in order to determine the age of the proteins,» says Max Planck research group leader Liepe. The scientists also analyzed how the frequency of proteins changes over time. To do this, they recorded a protein inventory in the ovary with almost 8,900 proteins.

The result: ovaries have an extremely high number of long-lasting proteins – more than other tissues and even more than the brain. These are found not only in the egg cells themselves, but also in other body cells in the ovary.

«Many of the long-lived proteins have protective functions, such as repairing DNA or protecting cells from damage,» explains Urlaub, who conducts research at the MPI and the University Medical Center Göttingen (UMG). The molecular folding helpers, so-called chaperones, ensure, for example, that misfolded proteins do not clump together and disrupt cellular processes. As the experiments of the Göttingen scientists showed, chaperones in the ovary are extremely stable and prevent clumping for longer than in the brain, for example. The power plants within the egg cells, the mitochondria, also contain particularly long-lived proteins. Since mitochondria are passed on from mother to offspring, it is extremely important that these organelles remain healthy.

Less long-lasting proteins in old age

«However, the concentration of many of these long-lived proteins in the ovaries and egg cells decreases with age. Proteins that are associated with acute inflammation and an immune response, on the other hand, increase with age,» reports Schuh. This is consistent with previous findings on increased inflammatory reactions in the ovaries of older women. «The complex protein network in the ovaries is therefore changing. The gradual disappearance of long-lived proteins from the ovaries and egg cells could explain why fertility in female mammals decreases after a certain age.»

Scientific contacts:
Prof. Dr. Melina Schuh
Department of Meiosis
Max Planck Institute for Multidisciplinary Sciences, Göttingen
Tel. +49 551 201-26000

Dr. Juliane Liepe
Research Group Quantitative and Systems Biology
Max Planck Institute for Multidisciplinary Sciences, Göttingen
Tel.: +49 551 201-1471

Prof. Dr. Henning Urlaub
Research Group Bioanalytical Mass Spectrometry
Max Planck Institute for Multidisciplinary Sciences, Göttingen
Tel.: +49 551 201-1060

Original publication:
Harasimov, K.; Gorry, RL; Welp, LM; Penir, SM; Horokhovskyi, Y.; Cheng, S.; Takaoka, K.; Stützer, A.; Frombach, A.-S.; Taylor Tavares, AL; Raabe, M.; Haag, S.; Saha, D.; Grewe, K.; Schipper, V.; Rizzoli, SO; Urlaub, H.; Liepe, J.; & Schuh, M.: The maintenance of oocytes in the mammalian ovary involves extreme protein longevity. Nat Cell Biol (2024).

Additional Information: – Original press release – Website of the Meiosis Department, MPI for Multidisciplinary Sciences – Website of the Quantitative and Systems Biology Research Group, MPI for Multidisciplinary Sciences – Website of the Bioanalytical Mass Spectrometry Research Group, MPI for Multidisciplinary Sciences


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