Short-Term Study Investigating the Estrogenic Potency of Diethylstilbesterol in the Fathead Minnow (Pimephales promelas)

Diethylstilbestrol (DES) is a synthetic estrogen that
has been
banned for use in humans, but still is employed in livestock and aquaculture
operations in some parts of the world. Detectable concentrations of
DES in effluent and surface waters have been reported to range from
slightly below 1 to greater than 10 ng/L. Little is known, however,
concerning the toxicological potency of DES in fish. In this study,
sexually mature fathead minnows (Pimephales promelas) of both sexes were exposed to 1, 10, or 100 ng of DES/L of water
in a flow-through system. Tissue concentrations of DES and changes
in a number of estrogen-responsive end points were measured in the
fish at the end of a 4 d exposure and after a 4 d depuration/recovery
period in clean water. Accumulation of DES was sex-dependent, with
females exhibiting higher tissue residues than males after the 4 d
exposure. The observed bioconcentration of DES in the fish was about
1 order of magnitude lower than that predicted on the basis of the
octanol–water partition coefficient of the chemical, suggesting
relatively efficient metabolic clearance by the fish. Exposure to
1, 10, or 100 ng of DES/L caused decreased testis weight and morphological
demasculinization of males (regression of dorsal nuptial tubercles).
Diethylstilbesterol induced plasma vitellogenin (VTG) in both sexes
at water concentrations ≥10 ng/L; this response (especially
in males) persisted through the end of the 4 d recovery period. Hepatic
transcripts of VTG and estrogen receptor-α also were affected
at DES concentrations ≥10 ng/L. Evaluation of transcript profiles
in the liver of females using a 15K-gene fathead minnow microarray
revealed a concentration-dependent change in gene expression, with
mostly up-regulated transcripts after the exposure and substantial
numbers of down-regulated gene products after depuration. Genes previously
identified as vitellogenesis-related and regulated by 17β-estradiol
were significantly enriched among those differentially expressed following
exposure to DES. Overall, our studies show that DES causes a range
of responses in fish at water concentrations comparable to those reported
in the environment and that in vivo potency of the estrogen is on
par with that of the better-studied estrogenic contaminant 17α-ethinylestradiol.