210 Autism and Exposure to Environmental Chemicals
Although the data are not always consistent between experimental and
epidemiological studies, they suggest that some EDCs may adversely affect the
structure and/or function of the uterus, vagina, and anterior pituitary. Some
EDCs are also associated with abnormal puberty, irregular monthly cycle,
reduced fertility, infertility, endometriosis, fibroids, preterm birth, and adverse
birth outcomes [126].
Limited information is available to explain the inconsistencies in findings
among studies and to explain the mechanisms by which EDCs adversely affect
female reproduction. Thus, more research is needed in this area [127].
Many potential EDCs have not been examined at all in experimental or
epidemiological studies. There are two major reasons for this paucity of infor
mation. First, there are so many synthetic chemicals being made as fragrance
and food flavors that it is not possible to keep up with this rapidly expanding
market [65,66]. Secondly, cosmetic and fragrance laws currently do not require
the industries who are marketing the products to test cosmetics, fragrances,
and food fragrances (i.e., flavors) for their safety. Even if some products are
tested, adult rodents are often used in the limited safety tests, with no assess
ment of potential adverse effects on fetuses, as detailed by Bioscience, and
backed up with 20,000 pages of documents [44]. Thus, there is a real and urgent
need for future studies to focus on the effects and mechanisms by which fra
grances, food flavors, and EDCs affect fetal development and reproductive
systems in both experimental and epidemiological studies.
Natural mutations or hormonal abnormalities have been extremely informa
tive in helping us better understand the consequences of disturbances in the
developmental processes described above, including their consequences on
male brain and reproductive organs (shown in Figure 7.13 and Table 7.1).
Genetic mutations affecting testosterone levels or AR expression or function
cause testicular dysgenesis syndrome (TDS), including cryptorchidism, hypo
spadias, impaired semen quality, and markedly increased risk of testicular
cancer [126]. The mutations encompass a large number of genes, including
those that encode ARs, key steroidogenic enzymes, and regulatory transcrip
tion factors. We already are aware that ASD has a multifactorial etiology, and
environmental factors play an important role. EDCs that can mimic testoster
one or bind ARs can have detrimental effects on the developing fetal brain and
may contribute towards the development of the gender bias of ASD observed
in male children [127].
Considering the importance of normal androgen activity in male reproduc
tive development and function, it is not surprising that chemical compounds
that disrupt androgen production or activity can cause ASD more often in
males than females. Although there are no equivalent animal models for human
ASD, since our brains are so large and unique, it is still meaningful to test
the EDCs that disturb testosterone balance in human fetuses on developing
primordial neurons for potential adverse effects. Animal models show that