Mothers pass on the legacy of stress exposure to future generations

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A mother’s response to stress can even affect her grandchildren.

Biologists at the University of Iowa have found that mothers of roundworms exposed to heat stress have, under certain conditions and through modifications of their genes, inherited this stress not only for their offspring, but even for the children of their offspring.

Researchers led by Professor Veena Prahlad of the Department of Biology and the Aging of the Mind and Brain Initiative have studied how the mother roundworm reacts when she feels danger, such as a change in temperature, which can be a harmful or even deadly animal. In a study published last year, biologists found that the mother roundworm releases serotonin when she senses danger. Serotonin travels from its central nervous system to warn its unfertilized eggs, where the warning is stored, so to speak, and then passed on to offspring after conception.

There are many examples of such genetic cascades, even in humans. Studies have shown that pregnant women affected by the famine in the Netherlands between 1944 and 1945, known as Dutch Hunger Winter, gave birth to children who were affected by the episode as adults; with a higher incidence than the average for obesity, diabetes and schizophrenia.

In this study, biologists wanted to find out how stress memory was stored in an egg cell.

Genes have “memories” of past environmental conditions, which in turn affect their expression, even if those conditions have changed. It is not clear how this “memory” is created and how it persists after fertilization, embryogenesis and after the embryo has developed into an adult. “The reason is that during embryogenesis, most organisms typically reset any changes that have been made to the genes due to their past activity.”

Veena Prahlad, Associate Professor, Department of Biology and the Aging Initiative of the Mind and Brain

Prahlad and her teams turned to roundworms, creatures regularly studied by scientists, looking for clues. They exposed the mother to roundworms to unexpected stress and found that stress memory was rooted in the mother’s eggs by a protein called heat shock transcription factor or HSF1. HSF1 protein is present in all plants and animals and is activated by changes in temperature, salinity and other stress factors.

The team found that HSF1 recruits another protein, an enzyme called histone 3 lysine 9 (H3K9) methyltransferase. It usually acts during embryogenesis to silence genes and erase the memory of their previous activity.

However, Prahald’s team observed something completely different.

“We found that HSF1 cooperates with mechanisms that normally act to ‘reset’ the memory of gene expression during embryogenesis to create that stress memory instead,” says Prahlad.

One of these newly silenced genes encodes the insulin receptor, which is central to metabolic changes with diabetes in humans and which, when silenced, alters the animal’s physiology, metabolism, and stress resistance. Because these silencing tags persisted in offspring, their stress response strategy was changed from a strategy that depended on their ability to respond highly to stress, rather than relying on mechanisms that reduced stress response but provided long-term protection against stress. environment.

“We found it all the more remarkable that if the mother was exposed to stress for a short time, only the offspring that developed from her germ cells, which were exposed to this stress in utero, had this memory,” says Prahlad. “The offspring of these offspring (the mother’s grandchildren) lost this memory. However, if the mother was exposed to prolonged stress, a generation of grandchildren retained this memory. Somehow the ‘dose’ of the mother’s stress exposure is population.”

Researchers plan to further investigate these changes. HSF1 is not only required for resistance to stress, but also elevated levels of both HSF1 and sedative markers are associated with cancer and metastases. Because HSF1 exists in many organisms, its newly discovered interaction with H3K9 methyltransferase to silence the gene is likely to have greater effects.

The paper “Gene bookmarking by the heat-shock transcription factor programs the insulin-like signaling pathway”, was published online on October 13 in the magazine Molecular cell.

Iowa co-authors include Srijit Das and Sehee Min of the Department of Biology and the Aging Mind and Brain Initiative.

The research was funded by national health institutes.

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