New findings from a team of Australian scientists suggest increased exposure to testosterone during pregnancy, triggered by a vitamin D deficiency, may be one of the causal factors explaining why autism spectrum disorder (ASD) is more common in boys.
A compelling 2016 study, led by a research team from the University of Queensland (UQ), provided strong evidence to suggest pregnant women who were vitamin D deficient at 20 weeks gestation were more likely to have a child with autistic traits by the age of six. A new study from the same team is now homing in on the causal mechanisms that could explain this association.
“The biological cause of autism spectrum disorder is unknown but we have shown that one of the many risk factors – low vitamin D in mothers – causes an increase in testosterone in the brain of the male fetuses, as well as the maternal blood and amniotic fluid,” explains Darryl Eyles, from the UQ’s Queensland Brain Institute.
Why boys are three times more likely to develop ASD than girls has been a mystery for many years. One explanation, dubbed the "prenatal sex steroid" hypothesis, suggests excessive prenatal exposure to testosterone could contribute to the development of ASD.
This new study, published in the journal Molecular Autism, explored the relationship between vitamin D and testosterone levels. In animal models the researchers showed how vitamin D deficiency leads to a particular response in male fetuses only.
“In addition to its role in calcium absorption, vitamin D is crucial to many developmental processes,” says Eyles. “Our research also showed that in vitamin D-deficient male fetuses, an enzyme which breaks down testosterone was silenced and could be contributing to the presence of high testosterone levels.”
This study is the first to offer a robust mechanism showing how a vitamin D deficiency can directly lead to increased testosterone levels in the brains of male fetuses. There are still, however, many unanswered questions surrounding exactly how increased exposure to testosterone in utero can lead to ASD in male children.
“Testosterone is key early factor and plays important role in the development of sexually dimorphic brain regions in human and also has profound effects on several neuronal processes during brain development such as neurogenesis, migration and immune functions,” the researchers hypothesize in the newly published study. “This remains an intense area of research.”
Eyles notes this relationship between vitamin D and testosterone is likely only one of many factors that could heighten ASD risk. Further research is necessary to not only understand how increased levels of testosterone could influence ASD development, but also to explore what other known ASD risk factors may have this effect on fetal testosterone.
“We have only studied one risk factor for ASD – vitamin D deficiency during development – our next step is to look at other possible risk factors, such as maternal stress and hypoxia – lack of oxygen – and see if they have the same effect,” says Eyles.
The new study was published in the journal Molecular Autism.
Source: University of Queensland