Traumatic experiences during early childhood can affect the metabolism of generations to come, new study claims
These changes in the metabolites and related pathways and syntheses were also observed in the male offspring of these adult mice and not just for a single generation
Trauma, whether endured during childhood or adulthood, leaves an indelible imprint on your physical and mental health. Childhood trauma is particularly more difficult to deal with as studies show that it can lead to lifelong health issues, from depression and maladaptive sexual development to genital and urinary diseases.
A new study published in The EMBO Journal suggests that this long-term effect of childhood trauma may be more long-lasting than people know and, in fact, it may be able to impact their children and grandchildren. The researchers behind this study hypothesized that paternal exposure to traumatic stress affects the germline through the metabolic system, particularly through lipid-derived metabolites, which is then passed down to the offspring. To evaluate this hypothesis, the researchers conducted a two-fold study.
Effects of early trauma on a mouse model
In the first part of the study, the researchers created a mouse model of early postnatal trauma using male mice and their male offspring to evaluate how early life stress changes blood composition. They found that mice exposed to early life stress and separation from mothers have metabolic dysfunctions and behavioural deficits that are transmitted to the offspring across several generations.
The metabolic analyses of adult male mice showed major metabolic dysfunctions in polyunsaturated fatty acid (PUFA) metabolism, particularly in metabolites involved in the synthesis of alpha-linolenic (ALA), linoleic acid (LA) and arachidonic acid (AA) pathways. This, in turn, affected the synthesis of bile acids and the production of steroid hormones.
These changes in the metabolites and related pathways and syntheses were also observed in the male offspring of these adult mice and not just for a single generation. The effects of early-life trauma were seen on the metabolites of generations of mice offspring, indicating that a history of early childhood trauma in the paternal line can affect the metabolism of generations of males to come, leading to similar patterns of obesity and metabolic disorders.
Early childhood trauma and metabolism in humans
To evaluate if these findings in mice subjects also echoed among humans, the researchers conducted similar analyses in a cohort of 25 children aged six to 12 years (both boys and girls) from an SOS Children’s Village in Lahore, Pakistan. All the children had lost their fathers and had been separated from their mothers during the preceding year - these conditions resembled the mice model of the researchers. Since all the children also shared the same orphanage, lifestyle differences among them were minimum.
Blood and saliva samples were collected from all the children, plus some healthy children without a history of trauma as a control group. Analyses of blood serum of all children showed similar metabolic changes in ALA, LA and AA metabolites. What’s more, similar metabolite alterations were also observed in bile and steroid synthesis. These lipid metabolite changes were not observed in the samples collected from the control group, indicating that the findings of the mouse model do have similarities with the human participants.
Changes in receptors in sperms
Further experiments conducted by the researchers, to understand exactly how these changes in the metabolism of those with childhood trauma were passed onto their offspring, revealed that the changed lipid metabolites in traumatised children activated changes in a type of hormone receptor known as peroxisome proliferator-activated receptors (PPAR). PPAR plays a major role in gene expression and the sequencing of deoxyribonucleic acid (DNA), especially in sperm cells.
The researchers, therefore, found that this is the genetic mechanism through which metabolic dysfunctions are passed down the generations, highlighting the understanding that metabolic disorders faced by men today may be the result of the trauma their ancestors suffered through during their early childhood. The researchers concluded that better understanding of these genetic mechanisms can provide better methods and treatments so that adverse consequences of childhood trauma on later life and generations can be avoided.
For more information, read our article on Metabolic syndrome.
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