Researchers at the University of Strasbourg, France have found that exposure of human cells to the male hormone testosterone alters the gene expression of some of the genes that contribute to the risk of autism. The findings provide key insight into why autism risk is higher for males than females, at a ratio of 4:1.
It has long been known that during development, exposure to testosterone and other male hormones (androgens) impacts development. The new study shows that genes involved in the risk of autism are regulated by testosterone during important phases of brain development in a way that can impact brain development during infancy.
Co-senior authors Jean-Louis Mandel, M.D., Ph.D., and Amélie Piton, Ph.D., and colleagues exposed human pluripotent neural stems cells to the testosterone metabolite DHT. The exposure led to subtle changes in the expression of about 200 genes, some which have previously been associated with autism. Of the genes found to be regulated by DHT treatment included NRCAM, which is linked to the brain abnormalities and symptoms in ASD, and FAM107A, which has been reported to be increased in people with ASD. FAM107A also appeared to play a part in androgen's ability to increase cell numbers in the study.
"These effects of male hormones may therefore contribute to the increased sensitivity of the male brain to develop ASD when also exposed to other genetic or environmental factors," said Dr. Piton, suggesting that the biological explanation for the sex-specific inequality of autism points to a predisposition in males.
The study did not consider the impact of exposure to environmental factors associated with increased risk of autism, such as aluminum hydroxide. Other studies have shown that aluminum hydroxide, and mercury, both found in some vaccines, can harm important cellular processes such as mitochondrial function, protein folding, and normal cellular detoxification. Future studies focused on the interaction between testosterone and components of vaccines suspected of contributed to altered neurodevelopment are being planned.
The study was published in the Journal Biological Psychiatry.
For more information: Angélique Quartier et al. Genes and pathways regulated by androgens in human neural cells, potential candidates for the male excess in autism spectrum disorders, Biological Psychiatry (2018). DOI: 10.1016/j.biopsych.2018.01.002
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