Stress on mothers can influence biology of future generations

Date:
October 13, 2021
Source:
University of Iowa
Summary:
Biologists have found that mother roundworms can pass stress signals
to future generations. The biologists report a mother roundworm
exposed to a stressor can even under certain conditions pass the
memory of that exposure to their grandchildren.



FULL STORY ==========================================================================
A mother's response to stress can even influence her grandchildren.


========================================================================== Biologists at the University of Iowa found that roundworm mothers
subjected to heat stress passed, under certain conditions and through modifications to their genes, the legacy of that stress exposure not
only to their offspring but even to their offspring's children.

The researchers, led by Veena Prahlad, associate professor in the
Department of Biology and the Aging Mind and Brain Initiative, looked at
how a mother roundworm reacts when she senses danger, such as a change
in temperature, which can be harmful or even fatal to the animal. In a
study published last year, the biologists discovered the mother roundworm releases serotonin when she senses danger. The serotonin travels from her central nervous system to warn her unfertilized eggs, where the warning
is stored, so to speak, and then passed to offspring after conception.

Examples of such genetic cascades abound, even in humans. Studies have
shown that pregnant women affected by famine in the Netherlands from
1944 to 1945, known as the Dutch Hunger Winter, gave birth to children
who were influenced by that episode as adults -- with higher rates than
average of obesity, diabetes, and schizophrenia.

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

"Genes have 'memories' of past environmental conditions that, in turn,
affect their expression even after these conditions have changed,"
Prahlad explains.

"How this 'memory' is established and how it persists past fertilization, embryogenesis, and after the embryo develops into adults is not
clear. "This is because during embryogenesis, most organisms typically
reset any changes that have been made to genes because of the genes'
past activity." Prahlad and her teams turned to the roundworm, a creature regularly studied by scientists, for clues. They exposed mother roundworms
to unexpected stresses and found the stress memory was ingrained in the mother's eggs through the actions of a protein called the heat shock transcription factor, or HSF1. The HSF1 protein is present in all plants
and animals and is activated by changes in temperature, salinity, and
other stressors.



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

However, Prahald's team observed something else entirely.

"We found that HSF1 collaborates with the mechanisms that normally act to 'reset' the memory of gene expression during embryogenesis to, instead, establish this stress memory," Prahlad says.

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 an animal's physiology, metabolism, and stress resilience. Because these silencing marks persisted in offspring,
their stress-response strategy was switched from one that depended on
the ability to be highly responsive to stress, to relying instead on
mechanisms that decreased stress responsiveness but provided long-term protection from stressful environments.

"What we found all the more remarkable was that if the mother was
exposed to stress for a short period of time, only progeny that
developed from her germ cells that were subjected to this stress in
utero had this memory," Prahlad says. "The progeny of these progeny
(the mother's grandchildren) had lost this memory. However, if the mother
was subjected to a longer period of stress, the grandchildren generation retained this memory. Somehow the 'dose' of maternal stress exposure is recorded in the population." The researchers plan to investigate these
changes further. HSF1 is not only required for stress resistance but
also increased levels of both HSF1 and the silencing mark are associated
with cancer and metastasis. Because HSF1 exists in many organisms, its
newly discovered interaction with H3K9 methyltransferase to drive gene silencing is likely to have larger repercussions.



==========================================================================
The paper, "Gene bookmarking by the heat-shock transcription factor
programs the insulin-like signaling pathway," was published online
Oct. 13 in the journal Molecular Cell.

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

The National Institutes of Health funded the research.

========================================================================== Story Source: Materials provided by University_of_Iowa. Original written
by Richard C. Lewis.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Srijit Das, Sehee Min, Veena Prahlad. Gene bookmarking by the
heat shock
transcription factor programs the insulin-like signaling pathway.

Molecular Cell, 2021 DOI: 10.1016/j.molcel.2021.09.022 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211013114108.htm

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