136 Male Gender Bias and Levels of Male Hormones During Fetal Development
neurostimulations or selective neurocytotoxicity (Figure 5.1). However, deple-
tion of OXYR and AVPR1‐receptor positive neurons was only observed in
male, but not female, NBCs following fragrance exposure (unpublished data).
The question remains as to why would female neuronal cells be protective?
Two potential mechanisms have been hypothesized. The first forwards the
notion that X chromosome gene dosage could play a role in sex ratios if the
non‐silenced genes were protective. It is increasingly recognized that learning
difficulties are themselves a risk factor for ASD; therefore, any evaluation of
how the X chromosome may be protective will need further evaluation [65].
It is still unknown which X‐linked genes may be involved; however, genes
that regulate amygdala circuits (which are disrupted in ASD) are suspected.
In a mouse model of Turner syndrome, the maternally expressed gene xlr3b
was associated with cognitive flexibility, but a human orthologue has yet to be
identified.
Numerous hypotheses and thousands of articles have been published in the
peer‐reviewed literature defining the illnesses and proposing potential causes
of ASD. Through these studies it has been revealed that oxytocin‐ and AVP‐
positive neurons are underdeveloped in the brains of autistic children.
Development of these neurons within the highly integrated metabolic, endo-
crine, and neuropeptide systems is influenced by the environment in which the
brain develops, which may provide clues into the etiology of ASD. Our finding
that testosterone concentrations can impact on the fetal neurodevelopment
brings forth a new perspective to the pathogenesis of ASD and the potential
role of testosterone or synthetic chemicals that act like testosterone (either
directly or indirectly, and numerous other environmental agents) that may dis-
turb the finely orchestrated fetal brain development. These chemicals are per-
vasive in modern society and may be important contributing factor(s) in ASD.
Chemicals in fragrances may be harmful to developing fetal brains, as well as
to adults [31–55].
Searching for effective biomarkers is one of the most challenging tasks in the
research field of ASD. fMRI provides a noninvasive and powerful tool for
investigating changes in the brain functions including structural changes, con-
nectivity, differentiation, function, maturation, and metabolism of the brain of
children with ASD. We believe that future studies will uncover some important
biomarkers that may assist in the identification of ASD in children before they
are 3 years old.References
1 Lai MC, Lombardo MV, Baron‐Cohen S (2014). Autism. Lancet,
383 (9920):896–91.