Contribution of Fragrances to ASD 183efficiency of oxytocin to its respective receptor [5,6]. Interestingly, the
three female fetal brain cell lines that we tested did not show substantial
reduction in oxytocin‐receptor positive neurons, shedding light on the
extreme male bias for ASD. Increased susceptibility of male fetal brains to
synthetic chemicals that can reduce the numbers of oxytocin‐receptor
positive neurons, combined with the mutagenic ability of fragrances (and
perhaps other synthetic chemicals), may be the major contributors to ASD
and male bias [46]. It should be noted that when scientists are investigating
causes of autism and when they are looking at the etiology of ASD, they are
essentially looking for mutations found in the ASD child, particularly
de novo mutations, and associate these mutations with ASD symptoms. We
contend that the hundreds or even thousands of mutations reported so far
likely represent the secondary effects of synthetic chemicals since they are
highly mutagenic and not the primary cause of ASD. As we have shown, it
may be the depletion of specific progenitor neurons (i.e., oxytocin‐ and
AVP‐receptor positive neurons) that are most likely responsible for the
observed symptoms of ASD. Since, currently, there is no method for assess
ing the number of oxytocin‐receptor positive neurons present in the ASD
child, an alternate solution would be to examine other social mammals (i.e.,
meerkats, wolves, rabbits, gerbils, guinea pigs, etc.) exposed to fragrances
and other synthetic chemicals at equivalent doses during various stages of
their pregnancies. Support for the unusual vulnerability of oxytocin‐receptor
positive neurons came indirectly from numerous studies that revealed that
children with autism have significantly lower levels of plasma oxytocin and
AVP than their typical peers [47–52]. A recent study also showed that
mothers of ASD children have low levels of oxytocin and AVP, but high
levels of testosterone [48]. In addition, in children without ASD, lower
concentrations of oxytocin in plasma are associated with lower social and
cognitive functioning [47–57]. Furthermore, AVP, oxytocin, and their
respective receptors, share similar sequences in animals, allowing these
peptides to activate each other’s receptors [54,58–63]. Animal and human
studies have revealed sex differences in AVP and oxytocin, such that
males appear to have enhanced AVP and oxytocin functioning compared
with females; these differences, however, vary by brain region and species
[62–64]. We hypothesize that fragrances, which are complex chemical
mixtures, may have differential effects on human neural development and
differentiation.
To investigate these effects male and female origin NBCs have been used for
an in vitro developing fetal brain model. As mentioned previously, these cell
lines represent a suitable model since they possess biochemical properties of
human neurons in vivo [2–6,44]. Furthermore, these cell lines are acquired
from human tumors, which encourage continuous division and provide the
required quantities of cells for investigations without significant changes in
variability [2–5].