Research: Rats born to mothers under duress show effects of stress on genetic level

University of Haifa researchers say trauma before conception could cause neurological as well as behavioral changes.

DNA strand double helix 300 (photo credit: Jerome Walker)
DNA strand double helix 300
(photo credit: Jerome Walker)
An experiment on rats born to mothers under duress before they conceived could shed light on harmful effects from the Second Lebanon War or the security situation in the South, on the children of those who went through those difficult experiences, said University of Haifa researchers.
Research on rats conducted at the university showed exposure to stress before conception can cause changes in the expression of a gene linked to the stress mechanism in the ovum and later in the brain of the offspring from the time they are born.
The systemic similarity in many instances between human and rodent behavior raises questions about the trans-generational influences in humans as well, said Hiba Zaidan, a doctoral student working with researchers in the lab of Dr. Inna Gaisler-Salomon.
“If until now, we saw evidence only of behavioral effects, now we’ve found proof of effects at the genetic level,” Zaidan suggested.
Researchers said that it is the first time the genetic response to stress in rats was shown to be linked to the experiences their mothers underwent before they had even conceived them.
“We are learning more and more about inter-generational genetic transfer and in light of the findings, and in light of the fact that in today’s reality many women are exposed to stress even before they get pregnant, it’s important to research the degree to which such phenomenon take place in humans,” they said.
In previous studies in Prof. Micah Leshem’s lab, it was found that exposing rats to stress before they had even conceived (and even at their “teen” stage) influences the behavior of their offspring. In the current study, in cooperation with Leshem, the researchers sought to examine whether there was an influence on genetic expression.
In the study, which was recently published in the journal Biological Psychiatry, researchers focused on the gene known as CRF-1, a gene linked to the body’s stresscontrol system that expresses itself in many places in the brain under stress.
The researchers took 45-dayold female rats, who – in comparison with humans – were adolescents. Some of the rats were exposed to “minor” stress, which included changes in temperature and daily routine for seven days, and compared them to a control group that was not exposed to stress at all.
The rats were mated and conceived two weeks later.

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In the first part of the study, the researchers examined the eggs of the rats that were exposed to stress even before they conceived, and they found that at that stage there was enhanced expression of the CRF-1 gene. For the second part, the researchers examined the brains of newborn rats immediately after birth, before the mother could have any influence on them, and found that even at the neonatal stage, there was enhanced expression of the CRF-1 gene in the brains of the rats born to mothers who had been exposed to stress.
During the third stage, the researchers exposed the offspring – both those whose mothers had been exposed to stress and those whose mothers were not – to stress when they reached adulthood. It emerged that the expression of CRF-1 among the offspring was dependent on three factors: The sex of the offspring, the stress undergone by the mother and the stress to which the offspring were exposed. The female rats whose mothers had been exposed to stress and who themselves underwent a “stressful” behavioral test showed higher levels of CRF-1 than other groups.