The Questions of Developmental Biology

Whether heavy maternal alcohol consumption leads to fetal alcohol syndrome or fetal alcohol
effect may be due to the types of alcohol dehydrogenase isozymes in the mother and fetus
(McCarver-May, 1996). Thus, whether or not a compound is "teratogenic" depends on many
things, including the genes of the individuals exposed to it.
Endocrine Disruptors
Endocrine disruptors are exogenous chemicals that interfere with the normal function of
hormones. They can disrupt hormonal function in many ways.
1. Endocrine disruptors can mimic the effects of natural hormones by binding to their receptors.
DES (diethylstilbesterol; Chapter 17), is one such example.
2. Endocrine disruptors may block the binding of a hormone to its receptor, or they can block the
synthesis of the hormone. Finasteride, a chemical used to prevent male pattern baldness and
enlargement of the prostate glands, is an anti-androgen, since it blocks the synthesis of
dihydrotestosterone. Women are warned not to handle this drug if they are pregnant, since it
could arrest the genital development of male fetuses.
3. Endocrine disruptors can interfere with the transport of a hormone or its elimination from the
body. For instance, rats exposed to polychlorinatedbiphenyl pollutants (PCBs; see below) have
low levels of thyroid hormone. The PCBs compete for the binding sites of the thyroid hormone
transport protein. Without being bound to this protein, the thyroid hormones are excreted from the
body (McKinney et al. 1985; Morse et al. 1996).
Developmental toxicology and endocrine disruption are relatively new fields of research.
While traditional toxicology has pursued the environmental causes of death, cancer, and genetic
damage, developmental toxicology/endocrine disruptor research has focused on the roles that
environmental chemicals may have in altering development by disrupting normal endocrine
function of surviving animals (Bigsby et al. 1999).
Environmental estrogens
There is probably no bigger controversy in the field of toxicology than whether chemical
pollutants are responsible for congenital malformations in wild animals, the decline of sperm
counts in men, and breast cancer in women. One of the sources of these pollutants is pesticide
use. Americans use some 2 billion pounds of pesticides each year, and some pesticide residues
stay in the food chain for decades. Although banned in the United States in 1972, DDT has an
environmental half-life of about 100 years (Nature Genetics 1995). Recent evidence has shown
that DDT (dichloro-diphenyl-trichloroethane) and its chief metabolic by-product, DDE (which
lacks one of the chlorine atoms), can act as estrogenic compounds, either by mimicking estrogen
or by inhibiting androgen effectiveness (Davis et al. 1993; Kelce et al. 1995). DDE is a more
potent estrogen than DDT, and it is able to inhibit androgen-responsive transcription at doses
comparable to those found in contaminated soil in the United States and other countries. DDT and
DDE have been linked to such environmental problems as the decrease in the alligator
populations in Florida, the feminization of fish in Lake Superior, the rise in breast cancers, and
the worldwide decline of human sperm counts (Carlsen et al. 1992; Keiding and Skakkebaek
1993; Stone 1994; Swan et al. 1997). Guillette and co-workers (1994; Matter et al. 1998) have
linked a pollutant spill in Florida's Lake Apopka (a discharge including DDT, DDE, and
numerous other polychlorinated biphenyls) to a 90% decline in the birthrate of alligators and to
the reduced penis size in the young males.