Page 992 - The Toxicology of Fishes

972 The Toxicology of Fishes

Environmental Brain
signals

Hypothalamus
GnRH Exogenous
estrogen
Pituitary
FSH/LH
Liver
Exogneous Ovary
estrogen
Vitellogenin
Blood

Endogenous
estradiol-17β

FIGURE 25.1 Vitellogenesis in fish. The solid line indicates the normal pathway of vitellogenin induction in female fish.
Endogenous estrogen is produced by the ovary under the stimulation of FSH/LH; it passes into the circulation and induces
vitellogenin synthesis in the liver. The vitellogenin then passes into the circulation and is sequestered by the developing
oocytes and stored as yolk for the subsequent embryo. The dashed lines show the routes of exposure to exogenous estrogens
in fish: oral and/or across the gill and/or skin surfaces. In male fish exposed to estrogen, the vitellogenin produced by the
liver accumulates in the plasma (shown by the dotted line).

oocytes and stored as yolk to act as a nutrient reserve for the subsequent development of the embryo
(Tyler and Sumpter, 1996) (Figure 25.1). The production of VTG, therefore, is usually restricted to
females (Copeland et al., 1986; Tyler et al., 1996). Male fish, however, do contain the VTG gene, and
exposure to both natural and synthetic estrogens can trigger its expression, resulting in detectable
concentrations of VTG in the blood plasma (Chen, 1983; Sumpter and Jobling, 1995). The finding of
VTG in male plasma indicated that an estrogen was present in the water, and the presence of STW
effluent outfall upstream of the trout study site led to the hypothesis that the source of the estrogen was
in the effluent. These initial observations of intersex wild roach and induction of VTG in male trout
stimulated a series of investigations into the estrogenic properties of STW effluent.
In the late 1980s, a field study began in which caged rainbow trout were placed in effluents from
sewage treatment works receiving either domestic inputs alone or both domestic and industrial inputs
at 28 locations (covering all 10 Water Authority areas) throughout England and Wales (Purdom et al.,
1994). The fish were exposed to the effluent for 2 to 3 weeks, after which time the plasma was assayed
for VTG by radioimmunoassay (Sumpter, 1985). An additional five sites where the water supplies were
uncontaminated with STW effluent were chosen as reference sites. At a few sites, the effluent was lethal
to rainbow trout, but at the remaining sites where the fish survived the effluents were all found to be
strongly estrogenic (Purdom et al., 1994). There was variability in the degree of the vitellogenic response
in the fish deployed and it ranged from a 500-fold increase in plasma VTG up to over a 50,000-fold
increase. At some sites, concentrations of plasma VTG exceeded 100 mg/mL; concentrations higher than
those normally found in fully mature females (Tyler et al., 1990) (Figure 25.2). The variability in
magnitude of the vitellogenic response between the fish at the different sites was probably the result of
differences in the age and sex of the fish used at the different sites, the timing of fish deployment
(exposures to effluents at the different sites were conducted at various times of the year), and the strength
of the effluent to which the fish were exposed. Immature carp (Cyprinus carpio), a native U.K. cyprinid
fish, were also exposed to the effluents at some of the test sites, and they produced a vitellogenic response
similar to that in the trout (albeit less pronounced) (Purdom et al., 1994). These results clearly demon-
strated that effluent from sewage treatment works throughout England and Wales were estrogenic.
The phenomenon of estrogenic effluent is not confined to the United Kingdom. Similar studies exposing
fish to effluents from sewage treatment works, handling primarily domestic inputs, have been conducted
in many other countries: Germany—bream (Abramis brama) (Hecker et al., 2001); France—chub