Male fetuses produce androgens during critical stages of brain development when cells divide and develop into neurons. Androgens increase the spread of cells and prevent them from death, which explains the predisposition of boys to ASD by contributing to the excessive brain growth that is consistent for people with ASD during the first years of life.
In the study, co-senior authors Jean-Louis Mandel, M.D., Ph.D., and Amélie Piton, Ph.D., and colleagues used human pluripotent neural stems cells to model the cells that generate neurons during brain development. It was discovered that treatment with the testosterone metabolite DHT led to subtle changes in the expression of about 200 genes, several of which have previously been associated with ASD. Some of the genes most affected by DHT treatment included NRCAM, which has been linked to the brain abnormalities and symptoms in ASD.
“The 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 ASD points to a predisposition in males, rather than a protective effect in females.
The key genes identified are regulated by testosterone and thus, it was suggested that the list of genes that were altered by androgens in the study might be useful to identify new genes that might be involved in ASD or in other diseases that occur more often in males and to generate important insight into how male hormones might contribute to the increased male susceptibility to ASD.
Category(s):Autism spectrum disorders
Source material from Science Daily
