21 October 2015

Men pass on the stress response by inheritance

Ivan Zagorsky, Vesti 

It is known that hereditary information is encoded in genes, which, except for random mutations, remain unchanged throughout life. Therefore, it was initially believed that parents could share life experiences with their children only through behavioral means, such as education.

Nevertheless, scientists have long noticed that individual traits acquired by a person after birth under the influence of the environment can subsequently be inherited. Not so long ago, it turned out that the DNA of children whose parents often experienced severe stress works differently than that of their peers.

In their previous work, Tracy Bale from the University of Pennsylvania and her colleagues found that male mice that had been stressed for a long time before breeding, for example, constantly smelled the urine of a predator, had offspring with a blunted reaction to similar stimuli.

Then scientists compared the sperm of stressed animals with the biological material of their more calmly living relatives. The researchers found an increased content in the first of the so-called microRNAs, which are not involved in protein synthesis, but serve to regulate gene expression.

"At that time, we just showed that the microRNA levels were different, and it wasn't too interesting, so we wanted to find out what role these changes play," says Bale.

In the new study, biologists injected nine previously discovered microRNA species into mouse zygotes, after which they transferred the cell into the female's body for further fetal formation. In addition, a control group of mice was used in the experiment, to which zygotes were transplanted without additional microRNAs or with only one of their varieties.

When the resulting offspring grew up, the researchers tested their reaction to stress. And again, it turned out that at an average level of exposure, for example, when the animal was immobilized for a short time, less anti-stress hormone cortisone was produced in the body of mice that emerged from zygotes with several types of microRNAs.

In addition, this group showed changes in the expression of hundreds of genes of the paraventricular nucleus – the area of the brain responsible for regulating the response to stress. This inevitably had to affect the early development of the nervous system.

Then Bale's team set out to trace the effect of microRNAs after fertilization at the molecular level. It is known that these molecules are able to target matrix RNAs (mRNAs) and block the synthesis of individual proteins. Therefore, biologists have focused on maternal mRNAs that are preserved from the egg and remain active for a short period after fertilization in order to control the development of the zygote.

"Since maternal matrix RNAs continue to be translated during the first divisions of the zygote, it is generally assumed that the mother has an advantage in the early stages, while the father does not get the word," explains Bale in a press release Penn: Stressed Dads Affect Offspring Brain Development Through Sperm microRNA. "But we assumed that sperm microRNAs could attack maternal mRNAs and thus influence their translation."

In the second part of the work, the scientists again injected microRNAs into mouse zygotes, but this time they incubated them for eight hours, and then determined the level of gene expression in each individual cell. As expected, the microRNAs suppressed the activity of the maternal mRNAs. In particular, the genes involved in chromatin remodeling were affected.

Bale believes that during stress in males, microRNAs can be released from the epithelial cells that line the appendages of the testicles and enter the maturing and stored sperm cells there.

Now scientists are trying to determine which stress factors increase the production of microRNAs in male cells, and are also looking for a way to influence the process of hereditary transmission of an abnormal stress response.

More information about the results of the work of American scientists can be found in an article published in the journal PNAS (Rodgers et al., Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress).

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21.10.2015
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