Stress response patterns are transmitted from one generation to the next as soft-wired information that is not written into the genetic code. Stress response patterns can be transferred from one generation to the next via the germline, says a new study. The germline refers to the DNA in the egg and sperm cells that join to form an embryo. Egg and sperm cells are called the germ cells. Germline DNA is the source of DNA for all other cells in the body.
Transmitting stress response patterns across generations is the subject of a new study published in the journal Biological Psychiatry. Children of survivors of extremely stressful life events face adjustment challenges of their own, as has been most carefully studied among the children of Nazi Death Camp survivors.
Survivors of extremely stressful events
This "intergenerational" transmission of stress response has been studied predominately from the psychological perspective. However, recent research points to biological contributions as well, says a new study explained in the November 4, 2013 news release, "Transmitting stress response patterns across generations."
You can check out the original study's abstract of that article, "Prereproductive Stress to Female Rats Alters Corticotropin Releasing Factor Type 1 Expression in Ova and Behavior and Brain Corticotropin Releaseng Factor Type 1 Expression in Offspring" by Hiba Zaidan, Micah Leshem, and Inna Gaisler-Salomon.The article appears in the journal Biological Psychiatry, Elsevier, Volume 74, Issue 9 published on November 1, 2013. The new study was done with rats. But both human and animal studies indicate that vulnerability to stress may be heritable and that changes in germline may mediate some transgenerational effects.
Corticotropin releasing factor type 1 (CRF1) is a key component in the stress response
Researchers investigated changes in CRF1 expression in brain and ova of stressed female rats and in the brain of their neonate and adult offspring. Behavioral changes in adulthood were also assessed. For example, adult female rats underwent chronic unpredictable stress.
Scientists extracted mature oocytes and brain regions from a subset of rats and mated the rest 2 weeks following the stress procedure. CRF1 expression was assessed using quantitative reverse-transcription polymerase chain reaction. Tests of anxiety and aversive learning were used to examine behavior of offspring in adulthood, according to the study's abstract.
Children of survivors of extremely stressful life events face adjustment challenges of their own, as has been most carefully studied among the children of Nazi Death Camp survivors
This "intergenerational" transmission of stress response has been studied predominately from the psychological perspective. However, recent research points to biological contributions as well. Indeed, the new study just published in Biological Psychiatry demonstrates that offspring born to stressed mothers show stress-induced changes at birth, with altered behavior and gender-related differences that continue into adulthood.
"The notion that biological traits that are not coded by the sequence of DNA can be transmitted across generations is the focus of a field of research called epigenetics. This new paper implicates epigenetic regulation of a well-studied contributor to stress response, CRF1, in the intergenerational transmission of patterns of stress response," said Dr. John Krystal, Editor of Biological Psychiatry, according to the news release.
The researchers, led by Dr. Inna Gaisler-Salomon at University of Haifa in Israel, were interested in how stress modulates behavior and gene expression across generations. Previous studies in both humans and animals have shown that females exposed to stress even before they conceive can affect their children and even grandchildren.
In this study, they looked for a possible mechanism for these effects, focusing on the CRF1 gene. They studied adolescent female rats that went through a mild stress procedure before mating
Stress led to an increase in CRF1 expression in the frontal cortex, a brain region involved in emotional regulation and decision making. Also, there was a dramatic increase in CRF1 expression in the egg cells of stressed females.
In the offspring of stressed female rats, brain CRF1 expression was increased as well, already at birth. "It seems that CRF1 is a marker molecule that tracks the stress experience across generations, perhaps via the germline, and maternal care is minimally involved in this particular effect," explained Gaisler-Salomon in the news release.
They also found behavioral differences between the offspring of stressed and non-stressed females, particularly in tests of emotional and exploratory behavior
Interestingly, CRF1 expression was increased in adult daughters of stressed females, but only if the offspring themselves were exposed to stress. This indicates that in adults, CRF1 expression depends on the mother's stress experiences in combination with the individual's stress experience and their sex.
"So why is this important?" asked Gaisler-Salomon, according to the news release. "Traditionally, it was believed that only genetic information is transferred from generation to generation via eggs and sperm cells. This study contributes to the notion that soft-wired information that is not written into the genetic code also can be transferred from one generation to the next via the germline."
Many psychiatric illnesses, such as schizophrenia and posttraumatic stress disorder, are related to stress
Better understanding of the related mechanisms can contribute to the development of better diagnostics and improved treatments. The authors' affiliations, and disclosures of financial and conflicts of interests are available in the article.
The researchers' findings demonstrate that stress affects CRF1 expression in brain but also in ova, pointing to a possible mechanism of transgenerational transmission, according to the study's abstract. In offspring, stress-induced changes are evident at birth and are thus unlikely to result from altered maternal nurturance. Brain CRF1 expression in offspring depends upon gender and upon maternal and individual exposure to adverse environment.
In the study, researchers show that chronic unpredictable stress leads to an increase in CRF1 messenger RNA expression in frontal cortex and mature oocytes. Neonatal offspring of stressed female rats show an increase in brain CRF1 expression. In adulthood, offspring of stressed female rats show sex differences in both CRF1 messenger RNA expression and behavior. Moreover, CRF1 expression patterns in frontal cortex of female offspring depend upon both maternal and individual adverse experience.
Authors of the study are John H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available.