200 Autism and Exposure to Environmental Chemicals
observations is that androgenic steroids might be capable of exerting immuno‐
modulatory effects on the maturing lymphocytes within the thymic environ
ment and, upon maturing, the cells might no longer express the ARs. It also
suggests that if an EDC interferes with this special process, it may contribute
to development of autoimmunity, such as rheumatoid arthritis, lupus, celiac
disease, Sjogren’s syndrome, multiple sclerosis, type 1 diabetes, vasculitis, and
many other diseases [104].Why Testosterone is Essential for Engineering a Male Brain
As shown in Figures 7.9 and 5.2, testosterone is an essential part of the normal
development of male gonads that begins early in embryogenesis with the
differentiation of the testis from the bipotential gonad. The internal sex
organs arise as a consequence of the maintenance of the mesonephric ducts (or
Wolffian ducts) and the regression of the paramesonephric (or Müllerian
ducts) due to the testicular hormones testosterone and anti‐Müllerian hor
mone, respectively. The development of external genitalia, the scrotum, and
testicular descent are under the control of several genetic and hormonal path
ways. Testosterone and its metabolite dihydrotestosterone drive the masculini
zation of the external genitalia. Testicular insulin‐like peptide 3 is also necessary
for testicular descent. Timing of the hormone action is important. In humans,
normal androgen (testosterone) action during gestational weeks 8–15 is criti
cal for normal development of the genitalia (penile malformations arise during
this period), whereas development of sperm production capacity occurs over a
much broader time window that continues to puberty (Figure 7.10).
Interference of endocrine disruptors on the timing of male fetal develop
ment, especially brain development, can wreak havoc on the engineering of
the fetal male brain. The female reproductive system, even though much
complex and requires a proper structure and function for many organs, includ
ing the ovary, uterus, vagina, and anterior pituitary, does not require testoster
one during the early fetal life as shown in Figure 5.2. But, still, EDCs have
the potential to interfere with female reproduction by adversely affecting the
structure and/or function of female reproductive organs.
The male brain is engineered entirely differently than its female counterpart
and high levels of testosterone during weeks 8–24 of fetal development attests
to this unique engineering of the male brain.
The majority of our information regarding the differences between male and
female brain structures has been obtained from rodent animal models of fetal
development. New information is emerging from sheep and other larger size
mammals. So far, the research shows that exposure of the vertebrate brain to
testosterone during a critical period of fetal development establishes perma
nent sex differences in reproductive physiology as well as a broad spectrum of