Childhood trauma leads to metabolic changes across generations

People who experienced childhood trauma usually suffer lifelong consequences that impact their physical and mental health. And besides this, the children and grand-children of such individuals may also be affected as well.

Child suffering from trauma

Image Credit: fizkes/Shutterstock.com

In this specific form of inheritance, the egg and sperm cells do not pass on the data to offspring through their DNA sequence, similar to traditional genetic heredity, but instead, pass it through biological factors involving the epigenome that controls the activity of the genes. But the main question is how the signals activated by traumatic events manifest in the germ cells.

Our hypothesis was that circulating factors in blood play a role.

Isabelle Mansuy, Professor of Neuroepigenetics, Brain Research Institute, University of Zurich

Professor Mansuy also works at the ETH Zurich’s Institute for Neuroscience.

These findings are extremely important for medicine, as this is the first time that a connection between early trauma and metabolic disorders in descendants is characterized,” explained Professor Mansuy.

Mansuy and her group showed that childhood trauma indeed has a permanent effect on blood composition and that these modifications are also passed to the subsequent generation.

Traumatic stress leads to metabolic changes across generations

In her research work, Professor Mansuy employed a mouse model for early trauma that had been created in her laboratory. The model is used to investigate the effects of trauma in early postnatal life on male mice and how they are passed to their offspring.

To establish whether these early traumatic experiences have an effect on the composition of the blood, the team carried out multiple analyses and discovered large and major variances between blood from normal, non-traumatized control groups and blood from adult traumatized animals.

Modifications in lipid metabolism were specifically remarkable, wherein the blood of traumatized male mice contained higher concentrations of certain polyunsaturated fatty acids metabolites. The same changes were also seen in their offspring.

Even more remarkably, when the team chronically injected the serum of traumatized males into non-traumatized males, they observed that the offspring also developed metabolic symptoms of trauma—indicating a direct relation between germ cells and circulating factors and thus proving the theory that blood sends stress signals to the gametes.

Comparison with traumatized children

Next, the team examined whether analogous effects are also present in humans. For this, they organized a cohort of 25 children from an SOS Children’s Village in Pakistan who were separated from their mother and had lost their father, and examined their saliva and blood. When compared to kids from normal families, the orphans displayed a higher level of a number of lipid metabolites—similar to the traumatized mice.

These children’s traumatic experiences are comparable to those in our mouse model, and their metabolism show similar changes in blood. This demonstrates the importance of animal research for providing us with fundamental insights into human health.”

Isabelle Mansuy, Professor of Neuroepigenetics, Brain Research Institute, University of Zurich

Up to one-fourth of children worldwide experience abuse, violence, and neglect, that can result in chronic diseases later in their life, emphasizing the significance of Mansuy’s study.

Receptor interferes with gametes

Additional experiments led the researchers to identify a molecular mechanism through which lipid metabolites can send signals to the germ cells of animals.

PPAR, a receptor found at the cell surface, plays a major role in this process; it is stimulated by fatty acids and controls gene expression as well as DNA structure in various tissues. The team found that the PPAR receptor is upregulated in the sperm of traumatized males.

When the researchers artificially stimulated the PPAR receptor in male mice, it resulted in lower body weight and led to disruption in glucose metabolism—an effect that was also observed in their offspring as well as grand-offspring. These and other experiments led the team to infer that the activation of the PPAR receptor in sperm cells plays a crucial role in the heritability of metabolic dysfunctions induced by traumatic experiences in ancestors.

Trauma damages the health of offspring

Our findings demonstrate that early trauma influences both mental and physical health in adulthood and across generations, which can be seen in factors like lipid metabolism and glucose levels. This is rarely taken into consideration in clinical settings.”

Isabelle Mansuy, Professor of Neuroepigenetics, Brain Research Institute, University of Zurich

A better understanding of the fundamental biological processes could aid medical practitioners to overcome the late-onset outcomes of adverse life experiences in their patients in the days to come.

Source:
Journal reference:

Steenwyk, G. V., et al. (2020) Involvement of circulating factors in the transmission of paternal experiences through the germline. The EMBO Journal. doi.org/10.15252/embj.2020104579.

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