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Autism: male hormones could increase the prevalence among boys

Overlap between 1) the effects of male hormones (testosterone and other androgens) on neural stem cells and 2) genes and physiological pathways involved in brain development and/or 3) altered in individuals with autism spectrum disorders.

Genes and Pathways Regulated by Androgens in Human Neural Cells, Potential Candidates for the Male Excess in Autism Spectrum Disorder.

Quartier A(1), Chatrousse L(2), Redin C(1), Keime C(1), Haumesser N(1), Maglott-Roth A(1), Brino L(1), Le Gras S(1), Benchoua A(2), Mandel JL(3), Piton A(4).

Biol Psychiatry Aug. 15, 2018


Feb. 20, 2018

Boys are affected four times more than girls by certain developmental disorders of the nervous system, such as autism spectrum disorders. However, all the mutations identified on the sex chromosome X do not explain this gender bias. The work of Angélique Quartier, conducted under the direction of Amélie Piton and Jean-Louis Mandel, has shown that male hormones, such as testosterone and its derivatives, by regulating genes important for brain development, some of which are known to be involved in autism spectrum disorders, could increase the susceptibility of boys to developing these disorders. These results are published in Biological Psychiatry on February 8, 2018.


Autism spectrum disorders are characterized by social communication deficits and restricted interests and/or stereotyped repetitive behaviors, often associated with intellectual disabilities. Many studies have concluded that these disorders are much more common in men, but surprisingly, genetic studies to date have shown that while there are genes on the X chromosome involved in intellectual impairment and autistic disorders, there is no significant difference between girls and boys in the percentage of mutations on this chromosome. It has also been shown that there is a correlation between prenatal exposure to male hormones, called androgens, and the development of autistic traits. The role of these hormones during brain development in men may therefore increase their susceptibility to developing nervous system disorders such as autism spectrum disorders or intellectual impairment.

 

To better understand how androgens can affect brain development, researchers have chosen to study the effects of these male hormones on neural cells. In collaboration with I-stem researchers, they analyzed the effect of these male hormones on human neural stem cells and observed that androgens increase the proliferation of these cells by protecting them from cell death when they differentiate into neurons.

They also found that androgens regulate the expression of several hundred genes in human neural stem cells. Some of these genes are known to be particularly expressed in the brain cortex, also known as the grey matter, of individuals with autism spectrum disorders.

The effect of male hormones on the human neuronal stem cells proliferation and survival regulation and on the gene expression regulation associated with brain development may therefore contribute to the increased sensitivity of the male brain, while also exposed to other genetic and environmental factors, to the development of nervous system diseases, such as autistic spectrum disorders.

This study was funded by the ANR (HARTaGeNe project), the Fondation pour la Recherche Médicale and the Collège de France.

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