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People who experience traumatic experiences in their childhood often suffer long-term consequences that affect their mental and physical health. But your children and grandchildren can also be affected. In this special form of inheritance, sperm and egg cells do not pass on information to the offspring via their DNA sequence, as does classic genetic inheritance, but rather via biological factors that involve the epigenome, which regulates genome activity. The big question, however, is how the signals triggered by traumatic events are embedded in germ cells.

“Our hypothesis was that circulating factors in the blood play a role,” says Isabelle Mansuy, professor of neuroepigenetics at the Brain Research Institute at the University of Zurich and at the Institute for Neuroscience at ETH Zurich. Mansuy and her team have shown that childhood trauma has a lifelong impact on blood composition and that these changes are passed on to the next generation. “These results are extremely important for medicine as this is the first time that a connection between early trauma and metabolic disorders has been characterized in offspring,” explains Mansuy.

Traumatic stress leads to metabolic changes over generations

In her study, Mansuy used an early trauma mouse model that had been developed in her laboratory. The model is used to study how the effects of early postnatal life trauma on male mice are transmitted to their offspring. To determine whether these early experiences had an impact on blood composition, the researchers performed several analyzes and found large and significant differences between blood from adult traumatized animals and blood from normal, non-traumatized control groups.

Changes in lipid metabolism were particularly noticeable, with certain polyunsaturated fatty acid metabolites occurring in higher concentrations in the blood of traumatized male mice. The same changes were seen in their offspring. More notably, when the serum of traumatized men was chronically injected into non-traumatized men, the offspring of traumatized men also developed metabolic trauma symptoms that established a direct link between circulating factors and germ cells, thus confirming the hypothesis that blood signals stress to the men provides gametes.

Comparison with traumatized children

The researchers then examined whether there were similar effects in humans. To this end, they gathered a cohort of 25 children from an SOS Children’s Village in Pakistan who had lost their father and were separated from their mother, and analyzed their blood and saliva. Compared to children from normal families, the orphans – just like the traumatized mice – showed a higher content of several lipid metabolites.

“The traumatic experiences of these children are comparable to those in our mouse model, and their metabolism shows similar changes in the blood,” explains Mansuy. “This shows how important animal research is to gaining fundamental insights into human health.” Up to a quarter of children around the world experience violence, abuse, and neglect that can lead to chronic illness later in their lives, underscoring the importance of Mansuy’s research.

The receptor disrupts gametes

Further experiments led the team to discover a molecular mechanism by which lipid metabolites can transmit signals to the animals’ germ cells. PPAR, a receptor on the surface of cells, plays a key role in this. It is activated by fatty acids and regulates gene expression and DNA structure in numerous tissues. The researchers discovered that this receptor is upregulated in the semen of traumatized men.

The artificial activation of this receptor in male mice led to a lower body weight and impaired glucose metabolism – an effect that was also observed in their offspring and large offspring. These and other experiments led the researchers to conclude that PPAR activation in sperm plays an important role in the heritability of metabolic disorders caused by traumatic experiences in ancestors.

Trauma damages the health of the offspring

“Our results show that early trauma affects both mental and physical health in adulthood and across generations, which is reflected in factors such as lipid metabolism and glucose levels,” says Mansuy. “This is rarely taken into account in the clinical setting.” A better understanding of the underlying biological processes could help doctors prevent the late-onset consequences of adverse life experiences in their patients in the future.

Scientists unmask part of the puzzle of how trauma inheritance is mediated

More information:
Gretchen Steenwyk et al., Involvement of Circulating Factors in Germline Transmission of Paternal Experiences, The EMBO Journal (2020). DOI: 10.15252 / embj.2020104579 Provided by the University of Zurich

Quote: Early trauma affects metabolism across generations (2020, October 15), accessed October 16, 2020 from https://medicalxpress.com/news/2020-10-early-trauma-metabolism.html

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