218 Autism and Exposure to Environmental Chemicals
of urine samples in the USA and Asia confirmed previous work showing that
93% of people had detectable levels of BPA, but surprisingly also showed
that 81% had detectable levels of bisphenol S (BPS), illustrating the widespread
use of this poorly known bisphenol analogue in consumer products.
The physiological effects of BPA on human adults are well documented, but
the mode of BPA action on the developing brain has yet to be examined in
primates, especially in the hypothalamus, which plays an important role in the
neuroendocrine system, neurodevelopmental disorders, and directly impacts
on human health (e.g., obesity, precocious puberty, anxiety, and hyperactivity).
BPA is commonly thought to exert its effects by acting as a weak ER competitor
that binds to ER receptors instead of the natural estrogen. However, interfer
ence at ARs and thyroid receptors (ThRs) has been shown also. Proliferating
cells in the developing hypothalamus express ERs and ARs, and the roles of
estrogen and testosterone in regulating neurogenesis are rapidly being
researched. In the hypothalamus of rodents, as well as in sheep, exposures to
BPA during fetal development affect expression of the nuclear ER genes and
proteins. For example, several studies have shown that hypothalamic ERα pro
tein and mRNA expression was increased by prenatal and/or early postnatal
BPA. In female sheep, ERs in the MPOA were increased by BPA (50 μg/kg/day
or 5 mg/kg/day, from E15 to P21) in both sexes.
An elegant study carried out by Kinch et al. [138] demonstrated that BPA
exposure during a time point parallel to the second trimester in humans has
real and measurable effects on brain development and behavior of the zebrafish
brain. The study showed that BPS, a replacement used in BPA‐free products,
equally affects neurodevelopment. These findings suggest that BPA‐free prod
ucts are not necessarily safe and support a societal push to remove all structur
ally similar bisphenol analogues and other compounds with endocrine‐disruptive
activity from consumer goods. Their study results combined with numerous
reported physiological and behavioral studies carried out in humans begin to
point to the prenatal period as a BPA window of vulnerability and suggest that
pregnant women should limit exposure to plastics and receipts. Numerous
other animal studies have also demonstrated that a number of chemicals can
reduce circulating levels of thyroid hormone, including, but not limited to,
PCBs, PBDEs, some phthalates, and perchlorate. Some chemicals that affect
the thyroid system in animals have been shown to be associated with cognitive
deficits in humans.
Besides the hypothalamus, the hippocampus, developmental exposure of
male rats to BPA changed expression of the ERα gene and protein. This
observed effect was dependent upon the age at which ERα was measured, and
this effect was blocked by the ER antagonist.
Nearly all of the steroidogenic chemicals are detectable in the brain, with
each agent having unique developmental and brain region‐specific profiles.
Beginning with those enzymes necessary for cholesterol transport and side