Effects of Testosterone or AR Mimicking EDCs 211
anti‐androgens can act in a dose‐additive manner, which has challenged the
current no adverse effect levels because adverse outcomes have appeared
when animals have been exposed to a combination of chemicals far below their
individual levels. In addition to anti‐androgens, estrogens and dioxins cause
similar effects, via their equivalent ERs or ARs, respectively. The balance
between these hormone‐receptor pathways is also important, beyond the indi
vidual roles of each hormonal system. Because the bulk of studies have focused
on anti‐androgens, these are currently the main focus of EDC research in male
reproduction.
Effects of Testosterone or AR Mimicking EDCs
Here we would like to briefly discuss what sort of physical and anatomic effects
one can observe when humans are exposed to EDCs. Some EDCs like phtha
late esters (Table 7.1 and Figure 7.13), inhibit testosterone production, whereas
others block the AR (e.g., the pesticide DDE, and fungicides vinclozolin and
procymidone). Despite their dissimilar mechanisms of action, these chemicals
act in a dose‐dependent manner, with increased likelihood of adverse effects
when low doses of individual chemicals are combined in a mixture [128].
Flame retardants, PCBs, DDT, and dioxin have been assessed for their rela
tionships with cryptorchidism. Cryptorchidism is the absence of one or both
testes from the scrotum. It is the most common birth defect of the male genital
and about 3% of full‐term and 30% of premature infant boys are born with at
least one undescended testis. However, about 80% of undescended testes
descend by the first year of life, usually within 3 months of birth. Undescended
testes are associated with reduced fertility and increased risk of testicular cancer.
In addition, boys may suffer psychological problems. Without intervention, an
undescended testicle will usually descend during the first year of life, but to
reduce these risks, undescended testes can be brought into the scrotum in
infancy by a surgical procedure called an orchiopexy. Figure 7.14 summarizes
the data.
It is interesting to note that incidence of cryptorchidism at birth is increasing
in many developed nations [129].
The list of EDCs that have an anti‐testosterone (anti‐androgenic) effect is
growing (Table 7.1). The compounds that act at the ARs (i.e., antagonists or
partial agonists) include widely spread pesticide congeners such as dichlorodi
phenyldichloroethylene (DDE) and fungicides such as vinclozolin and procy
midone. The most alarming problem is that a much larger group of EDCs and
other synthetic chemicals disturb testosterone synthesis. Phthalates are well‐
documented examples of these chemicals. Interestingly, phthalates show vari
ation in effects on different species, whereas the effects of receptor antagonists
are similar over these species. Since testing is performed with rodent models,
