[The maternal effect in infantile autism: elevated DNA damage degree in patients and their mothers]
L N Porokhovnik1, S V Kostyuk1, E S Ershova1
1Research Centre of Medical Genetics, Moscow, Russia.
Insights
Oxidative stress may contribute to infantile autism through DNA damage. Mentally healthy mothers of autistic children show elevated DNA damage, suggesting a "maternal effect" in autism development.
Area of Science:
- Neurodevelopmental Disorders
- Genetics and Epigenetics
- Environmental Health
Background:
- Infantile autism is a developmental disorder affecting communication, cognition, and behavior, with unclear causes but known hereditary and environmental influences.
- Oxidative stress is implicated in autism pathogenesis, potentially causing genotoxic effects like DNA strand breaks.
- The "maternal effect" highlights the mother's physiological state during pregnancy as a potential environmental factor in fetal development.
Purpose of the Study:
- To investigate DNA damage levels in children with infantile autism and their mothers.
- To explore the role of oxidative stress and genotoxicity in the etiology of autism through maternal factors.
Main Methods:
- Utilized the DNA comet assay to evaluate DNA damage in autistic children and their mothers.
- Assessed comet tail moment and DNA percentage in the tail as indicators of DNA damage.
- Compared DNA damage levels between autistic children, healthy children, mothers of autistic children, and healthy women.
Main Results:
- Autistic children exhibited significantly higher DNA damage than healthy controls.
- Mothers of autistic children showed elevated DNA damage, comparable to their autistic children.
- Healthy mothers of autistic children displayed higher DNA damage than control women without autistic children.
Conclusions:
- Genotoxic factors present in healthy mothers may influence fetal development, contributing to autism via the maternal effect.
- The findings suggest an environmental maternal contribution to autism pathogenesis, linked to oxidative stress and DNA damage.
- Further research is warranted to elucidate the specific mechanisms of maternal genotoxicity in autism.
Abstract:
Infantile autism is a common disorder of mental development, which is characterized by impairments in the communicative, cognitive and speech spheres and obsessional stereotyped behaviour. Although in most cases, pathogenic factors remain unclear, infantile autism has a significant hereditary component, however, its etiology is also under the influence of environmental factors, including the condition of the mother's body during pregnancy ("maternal effect"). Oxidative stress is assumed to play a key role in the pathogenesis of infantile autism. It is known that oxidative stress has a prominent genotoxic effect, which is realized through inducing single and double strand breaks of the nuclear DNA. We evaluated the degree of DNA damage in patients with infantile autism and their mothers using DNA comet assay. The comet tail moment and DNA per cent ratio in the tail were assessed for each individual. The two parameters appeared to be strongly correlated (r=0.90). Mean and median values of both parameters were considerably higher in the sample of autistic children, than in age-matching healthy controls. Interestingly, these parameters were also elevated in healthy mothers of autistic children, with no difference from the values in the group of autistic children. The control group of healthy women of reproductive age, who had no children with autism, differed by the DNA comet tail moment from the group of mothers of autistic children, but did not differ significantly from the control group of healthy children. The results suggest that there are genotoxic factors in mentally healthy mothers of autistic children, which can determine the pathological process in the foeti via environmental "maternal effect" during gestation.
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