How Autism Develops in a Fetal Brain 37brain of mammals. The dysregulation of these two neuropeptides is associated
with alterations in behavior, particularly social interactions. Therefore, we
examined the neuromodifications of human fetal brain neurons of both males
and females through immunohistochemistry methodology. We demonstrated
that exposure to even extremely low (i.e., femtomolar level) concentrations of
fragrances led to morphological changes, shown through light microscopy in
the neuroblastoma cell lines. Of note, these fragrances significantly reduced
the oxytocin‐ and arginine vasopressin‐receptor positive neurons in the male
neuroblastoma cell lines. However, since they not do so in the female cell lines,
this may help explain why there is a male bias in ASD cases. Our oxytocin–
arginine vasopressin study was the first to demonstrate a plausible link between
what appears to be three interrelated phenomena: fetal exposure to fragrances;
depletion of oxytocin‐ and arginine vasopressin‐receptor positive neurons;
and the widely established male bias in ASD cases [10–13].
We are also comparing testosterone exposure levels that are reported to have
been found in the amniotic fluid of an experimental group of ASD children and
a control group of normally developing children during gestational weeks
9–14. This investigation may show that ASD results from epigenetic factors,
those that do not have direct genetic causation but rather emerge through
environmental exposure. Significantly, we have identified in fragrances more
than two dozen chemicals with testosterone and other properties that imitate
natural sex hormones, including benzophenone‐1, oxybenzone, tonalide, and
galaxolide (see Chapters 5 and 7). Other chemicals that have been linked to
increased human estrogen receptor expression include benzophenone‐1, ben
zophenone‐2, octinoxate, oxybenzone, benzyl salicylate, benzyl benzoate,
butylphenyl methylpropional, and synthetic musks such as musk ketone,
tonalide, and galaxolide. Moreover, thyroid hormone disruption has been asso
ciated with butylated hydroxy toluene, octinoxate, and benzophenone‐2 [3,7,8].
Each of these chemicals is used in most fragrances commonly sold today. Recall
that even at very small concentrations (at the femtomolar level), fragrances
embedded with these chemicals can prove mutagenic and even carcinogenic to
human fetal cell lines [8–13]. We discuss the roles of these two neurohormones
in further detail in Chapter 5.
Given the growing linkage of epigenetic factors to ASD causation, we pro
pose that the genetic approach to ASD may continue to be less fruitful and
productive in uncovering the genesis of autism than more careful examina
tions of environmental factors, including fragrances and other toxins that lead
to mutations, especially in fetal development, and that are carcinogens.
ASD prevalence is an alarmingly increasing problem, not only because of
greater public awareness but also because of actual diagnostic data. We argue
that the “spectrum” is the result of interference in the normal fetal brain devel
opment from the very early stages through to about two years after birth, as
illustrated in Figure 1.19.