Such delicate spermatozoa
The hereditary program of sperm changes significantly with age and under the influence of environmental pollution
RNF blog on Naked Science portal
An international team led by Russian scientists has learned how rat sperm cells change with age. In adult animals, methylation (suppression) of regions of genes responsible for the intrauterine development of offspring occurs more often than in young animals, which means that later paternity may be overshadowed by health problems of the next generation. But if toxic substances enter the body of the future parent at the perinatal age, these differences become less significant: in young rats, the regions of genes responsible for embryo development are also suppressed. These conclusions may also have implications for humans.
The results of the study are published in the journal Epigenomics (Pilsner et al., Aging-induced changes in sperm DNA methylation are modified by low dose of perinatal flame retardants). The study was carried out with the financial support of the Russian Science Foundation (RNF). "The results obtained in animal models require confirmation in human studies. But if large–scale epigenetic changes associated with age are also found in men's spermatozoa, this will serve as a serious argument in support of the warning of "deferred fatherhood" in modern society," says Oleg Sergeev, Candidate of Medical Sciences, head of the RNF grant project, head of the Epigenetic Epidemiology Group at the Research Institute of Physico-Chemical Biology (Scientific Research Institute of the Moscow State University named after A. N. Belozersky.
In the modern world, the problem of male infertility remains urgent: about 10-20 percent of men of reproductive age suffer from this disease. In addition, in the last 50 years there has been a general decrease in the number of spermatozoa in the sperm of men in Western countries, which is associated with stress, malnutrition, exposure to environmental pollutants, including those affecting the parents of men.
The situation is aggravated by the fact that people are increasingly postponing the birth of children: economic instability, the desire to achieve career heights, the growth of life expectancy and much more are affected. Although the self-renewal of primary germ cells allows the production of spermatozoa for life, the accumulation of genetic and epigenetic errors prevents the normal course of this process.
The course of the experiment: pregnant rats were exposed to a toxic substance; sperm samples were taken from mature male cubs for analysis / ©Pilsner et al.
Epigenetic changes include chemical modifications of DNA that do not affect the nucleotide sequence of the molecule itself. Usually they are aimed at adapting the body to changing environmental conditions, but sometimes they are destructive.
It's all about the specifics of the sites where this happens. For example, methylation of certain sections of sperm DNA may be associated with such consequences in offspring as leukemia, autism, attention deficit disorder and even stillbirth. This is explained by the fact that the addition of a methyl group to the nucleotide cytosine in the gene leads to the suppression of the latter.
Scientists from the Research Institute of the Belozersky Moscow State University together with colleagues decided to analyze how age affects DNA methylation. To do this, they collected and studied the sperm of male rats on the 65th and 120th days after birth, which roughly corresponds to adolescence and adulthood in humans. In addition, to study the effect of pollutants, one of the groups of animals was exposed to a toxic substance in the perinatal period, covering the late stages of fetal development, childbirth and the first days after birth.
As a result of the study, it turned out that at a late age, active DNA methylation of sperm occurs in the areas responsible for the development of the embryo, including its brain. Consequently, later paternity may be overshadowed by the health problems of the descendants. Among rats exposed to such an environmental pollutant as the inhibitor ("suppressor") of gorenje tetrabromodiphenyl ether, methylation was higher in adolescent rats than in adults.
Thus, a kind of "epigenetic aging" of young individuals brought their sperm DNA methylation rates closer to those of mature rats. At the same time, age-related DNA modifications turned out to be similar to changes in small non-coding RNA studied by scientists before: in both cases, the same genes were mainly affected, and the effect of convergence of indicators in rats of different ages was also observed when exposed to a toxic substance.
"In the future, it is necessary to analyze such molecular mechanisms as histone modification, histone replacement with protamines and oxidative stress, which will allow us to better understand the epigenetic changes caused by age and the external environment," sums up Alexander Suvorov, Doctor of Biological Sciences, leading researcher of the Epigenetic Epidemiology Group of the Belozersky Moscow State University Research Institute of PHC.
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