The Questions of Developmental Biology

Dioxin, a by-product of the chemical processes used to make pesticides and paper
products, has been linked to reproductive anomalies in male rats. The male offspring of rats
exposed to this planar, lipophilic molecule when pregnant have reduced sperm counts, smaller
testes, and fewer male-specific sexual behaviors. Fish embryos seem particularly susceptible to
dioxin and related compounds, and it has been speculated that the amount of these compounds in
the Great Lakes during the 1940s was so high that none of the lake trout hatched there during that
time survived (Figure 21.23; Hornung et al. 1996; Zabel and Peterson 1996; Johnson et al. 1998).
Some estrogenic compounds may be in the food we eat and in the wrapping that
surrounds them, for some of the chemicals used to set plastics have been found to be estrogenic.
The discovery of the estrogenic effect of plastic stabilizers was made in a frightening way.
Investigators at Tufts University Medical School had been studying estrogen-responsive tumor
cells. These cells require estrogen in order to proliferate. Their studies were going well until
1987, when the experiments suddenly went awry. Then the control cells began to show the high
growth rates suggesting stimulation comparable to that of the estrogen-treated cells. Thus, it as if
someone had contaminated the medium by adding estrogen to it. What was the source of
contamination? After spending four months testing all the components of their experimental
system, the researchers discovered that the source of estrogen was the plastic tubes that held their
water and serum. The company that made the tubes refused to tell the investigators about its new
process for stabilizing the polystyrene plastic, so the scientists had to discover it themselves.
The culprit turned out to be p-nonylphenol, a chemical that is also used to harden the plastic of
the plumbing tubes that bring us water and to stabilize the polystyrene plastics that hold water,
milk, orange juice, and other common liquid food products (Soto et al. 1991; Colburn et al.
1996). This compound is also the degradation product of detergents, household cleaners, and
contraceptive creams. A related compound, 4-tert-pentylphenol, has a potent estrogenic effect on
human cultured cells and can cause male carp (Cyprinus carpis) to develop oviducts, ovarian
tissue, and oocytes (Gimeno et al. 1996).
Some other environmental estrogens are polychlorinated biphenyls (mentioned earlier).
These PCBs can react with a number of different steroid receptors. PCBs were widely used as
refrigerants before they were banned in the 1970s when they were shown to cause cancer in rats.
They remain in the food chain, however (in both water and sediments), and they have been
blamed for the widespread decline in the reproductive capacities of otters, seals, mink, and fish.
Some PCBs resemble diethylstilbesterol in shape, and they may affect the estrogen receptor as
DES does, perhaps by binding to another site on the estrogen receptor. Another organochlorine
compound (and an ingredient in many pest- icides) is methoxychlor. Pickford and colleagues
(1999) found that methoxychlor blocked progesterone-induced oocyte maturation in Xenopus at
concentrations that are environmentally relevant. This would severely inhibit the fertility of the
frogs, and it may be a component of the worldwide decline in amphibian populations.