Will fasting help with infertility and chromosomal abnormalities of the fetus?

Researchers at the Massachusetts General Hospital have demonstrated that keeping female mice on a low-calorie diet prevents the appearance of various abnormalities in their eggs, such as additional or missing chromosomes. Such disorders are quite common in the eggs of aging female mammals.

According to the head of the study, Professor Jonathan Tilly, in the mouse model, calorie restriction of the diet prevents the appearance of almost all signs of age-related decline in the quality of eggs.

The results of earlier studies by Professor Tilly's group showed that female mice, kept on a low-calorie diet for almost the entire adult life, retained the ability to reproduce until a very old age, even if uncontrolled access to food was resumed. Now scientists have managed to identify a gene, manipulations of which allow simulating the effects of a low-calorie diet and improving the quality of eggs of aging animals without reducing the caloric content of the diet.

Animals kept on a low-calorie diet, but not leading to exhaustion, live longer and show fewer signs of aging compared to control animals with unlimited access to food. This has been proven repeatedly, including in twenty years of experience with rhesus monkeys.

The delayed effect of a low-calorie diet on a person is still being studied, but data have already been obtained on the improvement of a number of health parameters, including a decrease in blood cholesterol and other risk factors for cardiovascular diseases.

The key stage in the formation of spermatozoa and eggs is meiosis, a process that results in the separation of a precursor cell having two copies of each chromosome into two specialized germ cells containing each chromosome in a single copy. When mature sperm and egg merge, an embryo is formed, the cells of which have two copies of each chromosome, one of which belongs to the maternal organism, and the second to the paternal one. Disorders of meiosis, such as the absence of chromosomes or the appearance of additional ones, occur much more often in the eggs of aging animals, which increases the frequency of infertility, miscarriages and malformations, in particular Down's disease, the cause of which is an additional copy of chromosome 21.

The results have prompted researchers to study in more detail the metabolic factors mediating the effect of a low-calorie diet on reproductive health. At first, they observed two groups of female mice starting from early adulthood (3 months) and ending at 1 year – an age when the quality of eggs and the ability to conceive in ordinary mice is significantly reduced.

One group of animals had unlimited access to food throughout their adult life, and the second group was kept on a low-calorie diet for 7 months, after which, a month before the end of the study, they resumed unlimited access of animals to food.

In the first group, there was an expected age-related decrease in both the number of eggs released by the ovaries and the content of mature cells ready for fertilization among them. The reproductive status of the second group of animals practically did not change during the entire study period and remained approximately at the peak of reproductive age.

Analysis of the state of chromosomes and other disorders associated with meiosis revealed a significant number of abnormalities in the eggs of aging mice who had free access to food, which was not observed in the eggs of starving animals. Age-related mitochondrial disorders, such as the formation of their aggregates and a decrease in the level of ATP (the metabolic fuel of the cell synthesized by mitochondria), were also observed exclusively in the eggs of normally fed mice.

The mechanisms underlying the effects of a low-calorie diet are currently being actively studied, but it is already known that the DNA transcription regulator PGC-1-α is involved in several metabolic processes (for advanced readers: this protein is completely called "the receptor-gamma-coactivator-1-alpha activated by peroxisoMe proliferators"). It participates in the modulation of the activity of a number of genes that ensure the maintenance of a certain number of mitochondria in the cell and their normal functioning.

Researchers have demonstrated that the absence of a functioning PGC-1-alpha gene in mice with unlimited access to food has an effect on the condition of eggs similar to the effect of a low-calorie diet. However, the combination of the absence of this gene and a low-calorie diet did not lead to an increase in the effects observed when studying these two factors separately. Thus, it is obvious that PGC-1-alpha and a low-calorie diet are links of the same mechanism.

The researchers believe that if the effects they found can be reproduced in the human body without health risk, it will not only increase the chances of a large number of women having a child, but also minimize the likelihood of having children with Down syndrome and other chromosomal diseases.

Article by Kaisa Selesniemi et al. Prevention of maternal aging-associated oocyte aneuploidy and meiotic spindle defects in mice by dietary and genetic strategies is published on July 5 in the preliminary on-line version of Proceedings of the National Academy of Sciences.

Evgeniya Ryabtseva
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of Massachusetts General Hospital:
Study suggests new strategy to prevent infertility, birth defects.

12.07.2011