Some egg proteins remain without replacement for most of the female’s life.
We know that female mammals are born with a reserve of eggs that remain with them for the rest of their lives. Strictly speaking, these are not eggs, but so-called first-order oocytes, which then, after two divisions, produce a real egg ready for fertilization; but, be that as it may, the reserve of first-order oocytes (let’s call them immature eggs) is not replenished during life. At the same time, they are not stored frozen, they are living cells in which various processes occur – and life processes produce by-products and effects that are not always beneficial. The question arises as to how eggs manage not to deteriorate over time.
The mechanisms here may be different. Two years ago we wrote that immature eggs have a specially tuned energy metabolism – so that as few aggressive oxidative radicals as possible appear in the cell. Radical molecules oxidize biomolecules, disable them and provoke oxidative stress – so the egg tries to protect itself from them. There is a substance called spermidine, which helps eggs eliminate intracellular defects. Another possible mechanism is described in two recent articles in Nature Cell Biology and eLife – both are about proteins that make eggs last longer.
On average, protein molecules live in a cell for a day or two, or at most a few days (we are talking about mammalian cells). But there are examples of proteins that live exceptionally long: these are the proteins of the lens, some cartilage proteins; long-lived proteins are found in the brain. To find out whether such proteins are present in egg cells, the researchers used a similar experimental strategy in both cases: they fed female mice food with heavy isotopes of carbon or nitrogen. These heavy isotopes ended up in the synthesized protein molecules. When the females became pregnant, the isotopes also appeared in the embryos. But when the cubs were born, they began to be fed regular food, without isotopes. The cubs grew, the proteins in them were renewed, and the new molecules, naturally, did not carry any isotopes. However, some of the protein molecules remained with the isotopes – this meant that the mice had them from birth.
The staff of the Institute of Multidisciplinary Research write in Nature Cell Biologythat in two-month-old mice, about 10% of the proteins in the eggs were synthesized when the mice themselves were still in the womb. The young mice were again given isotopic food, for a certain period of time, to understand how often the proteins in their immature eggs are renewed. It turned out that about 10% of the proteins are destroyed by half (that is, half of the molecules of a particular protein are destroyed) in a hundred or more days – quite a long time, considering that mice do not live long at all. Some proteins remained in the eggs for most of the life of the mice. The researchers write that the preservation of proteins in the eggs is facilitated by enhanced antioxidant measures, as well as the active work of chaperones – special proteins that help other proteins maintain the correct three-dimensional configuration, without which they simply cannot function normally.
In the second article in eLife
Northwestern University researchers write about the same thing, but with different figures: that in seven-month-old mice, about 5% of the proteins in the eggs remain either from intrauterine development or are synthesized shortly after birth, and that by eleven months, 10% of this 5% remains intact.
Both articles also say that long-lived proteins are present not only in immature eggs, but also in ovarian cells that serve the eggs, providing them with a comfortable “habitat”. As for proteins, among them there are cytoskeleton proteins, mitochondrial proteins, chromatin proteins, a receptor that helps the sperm penetrate inside, and proteins that maintain the stability of other proteins. The cytoskeleton holds the internal structure of the cell and supports intracellular transport, energy metabolism reactions occur in the mitochondria, chromatin proteins work with DNA, structuring it and influencing gene activity. That is, long-lived proteins are not some special types of proteins, but ordinary proteins that are involved in important cellular processes and to which the egg gives a long life. The egg does not live all its time on a reserve of proteins from embryonic development, sooner or later it replaces them, it just replaces some less often than usual. Over time, mutations occur in DNA, even if the cell does not divide, and if proteins are frequently updated, there is a risk of activating a mutant protein. For normal cells, this may not be too bad, but for egg cells, it is desirable that such cases be fewer. (Here we can recall that, if we are talking about mitochondria, it is the mitochondria of the egg that the embryo gets at the very beginning, so it is even more desirable to preserve them without any molecular defects.)
At the same time, the long-term functionality of the proteins themselves also needs to be ensured somehow. That is, one of the reasons why egg cells do not spoil for a long time is not only the long-lived proteins, but also the ability of egg cells to give a long life to these proteins. It is still unclear to what extent the new results can be used in medical practice. Perhaps, if the ability of egg cells to preserve their proteins is stimulated, then the egg cells themselves will remain more suitable for conception for a longer time. Or perhaps such long-lived proteins will be used in diagnostic tests that determine the readiness of the reproductive system for conception and childbearing. But it will be possible to talk about tests and other things only after similar long-lived proteins are seen in humans too.
Source: www.nkj.ru
