The Questions of Developmental Biology

Deformed frogs: pesticides mimicking retinoic acid?
Throughout the United States and southern Canada there is a dramatic increase in the
number of deformed frogs and salamanders in what seem to be pristine woodland ponds (Figure
21.26A; Ouellet et al. 1997). These deformities include extra or missing limbs, missing or
misplaced eyes, deformed jaws, and malformed hearts and guts. Some of these malformations
(especially the limb anomalies, see Figure 3.23) may be due to trematode infestation, but other
malformations do not seem to be explainable by that route. Some lakes containing high
proportions of malformed frogs do not appear to be infested with trematodes, and water from
these lakes is able to disrupt development in frog eggs that are placed into it. It is not known what
is causing these disruptions, but there is speculation (see Hilleman 1996, Ouellet et al. 1997) that
pesticides (sprayed for mosquito and tick control) might be activating or interfering with the
retinoic acid pathway. The spectrum of abnormalities seen in these frogs resembles those
malformations caused by exposing tadpoles to retinoic acid (Crawford and Vincenti 1998;
Gardiner and Hoppe 1999). New research has focused on compounds such as methoprene, a
juvenile hormone mimic that inhibits mosquito pupae from metamorphosing into adults. Since
vertebrates do not have juvenile hormone, it was assumed that this pesticide would not harm fish,
amphibians, or humans. This has been found to be the case: methoprene, itself, does not have
teratogenic properties. However, upon exposure to sunlight, methoprene breaks down into
products that have significant teratogenic activity in frogs (Figures 21.26B,C). These compounds
have a structure similar to that of retinoic acid and will bind to the retinoid receptor (Harmon et
al. 1995; La Claire et al 1998). When Xenopus eggs are incubated in water containing these
compounds, the tadpoles are often malformed, and show a spectrum of deformities similar to
those seen in the wild (La Claire et al. 1998).