EPA/600/J-94/283
   Fish  Intersexuality  as  Indicator
            of  Environmental  Stress
 Monitoring fish reproductive systems  can serve to  alert humans
                                to potential harm
                          Stephen A. Eortone and William P. Davis
        Mike Ho well and Ann Black
        examined each diminutive
        fish in the minnow seine
haul they had made in the tea-col-
ored waters of a small coastal stream,
Elevcnmile Creek,  in the western-
most, panhandle area of Florida in
1 978. All the mosquitofish (Gambu-
sia af/'inis) appeared to be males. At
first, the researchers, then both at
Sntnford University in Birmingham,
Alabama, were not too surprised
because they were aware that among
mosquitofish populations there oc-
curs some microhabitat segregation
by sex  (Martin  1975). Moreover,
they knew differential mortality
could also lead to unequal sex  dis-
tributions (Snelson  1989). On closer
inspection, however, the scientists
noted an astonishing oddity.
  Many of the apparently male fish
(as distinguished by the presence of
a gonopodium, an elongation of the
anterior anal-fin rays that serves as
a copulatory organ to inseminate
females) bore what appeared to  be a
gravid spot, which in these live-bear-
ing fish normally indicates females
with internally developing young
(Figure  1). Later, a laboratory analy-
sis confirmed that many of the  fish
thought to  be male were actually
masculinized females (Howell et al.
1980).  These masculinized female
Stephen A. Bortone is a professor in the
Department of Ecology and Evolution-
ary Biology at the University of West
Florida, Pcnsacola, FL 32514. William
P. Davis is a  research ecologist at the
Environmental Research  Laboratory,
Gulf Breeze, FL 32561.
 Intersexuality  presents

    an opportunity for

   biologists  to design

  testing procedures to

  evaluate detection of

  endocrine-disrupting

          agents

mosquitofish showed, in addition
to a gonopodium, more subtle male
secondary sex characters, including
behavioral characteristics such as
pursuit and gonopodial swinging.
  Speculation on  the potential
causes of this masculinization ranged
from genetic phenomena to envi-
ronmental induction. The environ-
mental hypothesis gained strength a
few months later when  a  second
population of masculinized fish was
discovered in the Fenholloway River
(Bortone and Drysdale 1981), an-
other coastal  Florida stream, ap-
proximately 300 kilometers east of
Elevenmile Creek. The second group
included masculinized females from
two other live-bearing species in the
family Poeciliidae (the least killi-
fish,  Heterandria formosa  [Figure
2], and the sailfin molly, Poecilia
latipinna) as well as masculinized
female mosquitofish.
  In both streams, the masculinized
females occurred downstream of
paper mills discharging  kraft-mill
effluent (KME), but  they were not
upstream of the paper mill discharge
nor in any tributaries to the efflu-
ent-receiving streams. We observed
in least killifish a higher degree of
masculinization among females cap-
tured closest to a  KME discharge
point, and we saw proportionately
reduced mascuiinization in samples
collected downstream from the point
of  KME discharge  (Figure 3). The
phenomenon was not observed in
nonpoecilid  fishes inhabiting  the
streams, however.
  Fish  have long  been known to
display a wide range of variation in
the expression of their sexuality (Atz
1964). Moreover, investigators spe-
cializing in the reproductive biology
of fishes have noted a morphologi-
cal plasticity of their expressed sex
in response to changes  in environ-
mental factors (Reinboth 1980).
These factors include temperature,
pH, light intensity, and social con-
ditions, anong others. Careful ex-
amination of sexuality in fishes has
the potential to allow us to measure
the nature and extent of some types
of environmental stress  (Davis  and
Bortone 1992).
  In this article, we examine how
human modification of the environ-
ment through waste discharge has
altered the sexual condition of fishes.
We also examine  the degree  and
nature of fish intersexuality relative
to environmental stress. In addition,
we  show  how these sexual alter-
ations can serve as sentinels to alert
resource managers to potential prob-
lems.  Last, we indicate how  this
phenomenon can be used to direct
future research.
March 1994
                                                        165

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l-igurc 1. Normal female (top) and male
mnsquitofish (bottom). A masculinized
tvnv.ilc is pictured in the center, sho%v-
ing the gonopodial  elongation  of the
anal fin.
A few words about sex

Fish species arc extremely broad in
the expression of their reproductive
modes.  These modes  can vary be-
tween  phylogenctic lineages and
among members of the same family.
The tcrmintersexuality encompasses
a broad range of sexual expression
in which both male and female char-
acters, cither primary or secondary,
are found in a single  individual at
some time during its life.  Hertnaph-
roditisnt describes a subcategory of
intcrsexuality where the primary re-
productive characters (testes and
ovaries) are found in a single  indi-
vidual. The male and female charac-
ters can occur at the same time (as in
the small  sea  basses; e.g., Fischer
and  Percrsen 1987) or at different
ages (i.e., sex reversal). Individuals
can initially be male (described as
protandry, as in the anemone fishes;
e.g., Fricke and Fricke  1977)  or fe-
male (termed protogyny. as in  the
groupers; e.g., Moe 1969) . Mascu-
linization, called  arrhenoidy,  is a
subcategory of intersexuality where
the presence of male secondary  sex
characters is observable in females.
It should not, however, be  concep-
tually confused with hermaphrodit-
ism, sex reversal, or "adaptive am-
biscxuality" (Reinboth 1988), where
sex change is part of a species' nor-
mal, reproductive mode.
   Induced alterations  of sexuality
in fishes have been well documented
(see review by Reinboth 1980).  For
example, salmon are known to at-
tain sexual maturity earlier in their
development when treated with go-
nadotropins  (Funk and Donaldson
1972).  In  laboratory  experiments
pregnant-mare serum,  chorionic
gonadotropin,  X-rays, and incom-
plete hypophysectomy have all been
used to  produce arrhenoidy in fe-
male swordtails. Additionally, more
naturally occurring phenomena such
as  old age or parasitism have also
been associated with  masculiniza-
tion  among  fishes, including  gup-
pies (Atz 1964).

The complex nature of paper
mill effluent

The preparation  of wood pulp for
paper and  cellulose manufacture
separates cellulose fibers and ligntHfl
from the sugars,  saps,  and other
components  (including animal in-
habitants)  of tree stems. Different
paper mills  use  variations of the
pulping  process depending on the
materials being processed (e.g., pine
or  hardwoods) and the end product
(e.g., bulk  cellulose, brown kraft
paper, and white paper).
    Basic to all the pulping processes
is separation and  discharge of sug-
ars, lipids,  resins, and fatty acids
that  are the digestion by-products
of  kraft-mill operations. Typically,
these waste products are entrained
in heated waters that are directed to
settling and  aeration ponds. There
they receive bacteriological treat-
ment analogous to sewage treatment
processes. Plants, especially  pine
trees, are potentially rich sources of
phytosterols (Conner et al. 1976).
However, owing to the structure of
the complex resins and sugars, there
is an inherent resistance to a rapid
breakdown into humic and  fulvic
acids. The treatment processes also
appear not to destroy phytosterols,
some of which masculinize poeciliid
fishes in the laboratory.
  The complexity of paper-mill ef-
fluent presents a considerable chal-
lenge to specific identification  of
androgenic factors.  On one  hand,
there is the presence of various phy-
tosterols, which have been shown to
induce masculinization  under con-
trolled  conditions  (Denton  et al.
1985).  Phytosterol action  may  be
influenced by a  variety of environ-
mfntal conditions, including the sea-
sons, tree species being pulped, de-
gree  of effluent  treatment, and
effluent dilution. We have chosen to
assess phytosterol activity.
   On the other hand, the chemical
processes within a mill (e.g., chlo-
rine, chlorine dioxide, or oxygen
bleaching) may add to the complex-
ity of the effluent  and thus may
influence  the production of dioxin,
which is known to be an endocrine
disrupter.  However, the literature
has  attributed feminization,  rather
than masculinization, to  dioxin
(Peterson et al. 1992). For this rea-
son, and  because dioxin  exposure
presents serious hazards, we have
chosen not to assess dioxin effects.
   Quantification  of pulp-mill ef-
fluent is typically done through com-
parative effects of whole and dilut-
ed  effluent samples.  Because the
.masculinization response in test fish-
es commences in microbially degrad-
ed phytosterols after 15-20 days of
exposure,  experiments  using efflu-
ent  samples  are cumbersome and
highly variable. To carefully assess
the androgenic effects of paper-mill
effluents, it is preferable to have a
direct connection to the effluent with
continuous, flow-through exposure.
Selectively filtered samples  would
allow fractionation analyses so that
identification of components  can be
determined by  their relative  activi-
ty. No research support that we
know of,  to date, has been  made
available  to conduct  such  experi-
ments.

Intersexuality and
paper-mill effluent

Fishes and other organisms  occur-
ring  in aquatic habitats receiving
166
                                             BiaScience Vol. 44 No. 3

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Figure 2. An array of anal fins from the least killifish. a. Normal female, b. Fish exposed to kraft-mill effluent; note the
incursvcl segmentation at the  tips  of the rays. c. Another example of  a fish exposed  to kraft-mill effluent with some
elongation  of the tin rays. d. Normal male gonopodium resembles this highly masculinized female fin.         '
pulp and paper-mill  effluents  ex-
hibit a variety of biochemical, physi-
ological, metabolic, and behavioral
responses  (Mel.cay  et al. 1987,
Owens  1991). Recent reports indi-
cate that paper-mill effluents in natu-
ral  waters can produce modifica-
tions in the life-history features of
fislu-s including adverse schooling
behavior  in whitefish (Myllyvirta
and Vuorinen  1989), changes in
maturity and serum steroid  levels in
while suckers  and lake whitefish
(Munkittrick et al. 1992),  and in-
creased  growth,   biochemical
changes, and higher levels of stress
in juvenile coho  salmon (McLcay
1979).  Juvenile  American  eels
(A»}*nilla rnstrata) from Elevcnmile
Creek  exhibited  precocious  male
secondary sex characters (enlarged
eyes and  precocious  testicular  de-
velopment; Caruso ct  al. 1988).
  KMK-induccd male secondary sex
characters  in  female  mosquitofish
occur under both field and labora-
tory conditions (Bortone ct al. 1989,
Davis  1989, Drysdale  1984, Drys-
dale and Bortone 1989, Rosa-Mol-
inar and Williams  1984).  We  ex-
posed female mosquitofish to stream
water  that had  received  naturally
degraded KME for three weeks both
in the  field and  in  the laboratory.
Several morphological characters
were  affected including anal-fin
length,  pre-anal  length,  dorsal-fin
height, pelvic-fin  height, intcrorbital
width, eye diameter, and body depth.
Each character changed to a more
masci'line  state. These  modified
characters were statistically signifi-
cant indicators of  KME  exposure
(Bortone et al. 1989). After three
weeks of exposure, the morphologi-
cal characters of KME-treated adult
females were  intermediate to  the
normal male and female conditions.
   Masculinization in female mos-
quitofish and other poeciliids is most
readily  observed  in  the increased
segmentation and elongation of the
third, fourth, and fifth  anal  rays
(Howcll and Denton 1989, Howcll
et al. 1980). These changes can be
observed in fish  exposed  to such
steroids as  methyltestosterone
(Turner  1960), androstenedione,
androstanol,  and spironolactone
(Hunsinger and Howell 1991).
   A hypothesis has been offered that
bacterial processes associated with
KME may  be responsible  for  the
arrhenoid condition among natural
populations of mosquitofish. Den-
ton et al. (1985) and  Howell  and
Denton (1989) exposed  mosquito-
fish  to phytosterols (i.e., sitosterol
and stigmastanol) mixed with a bac-
terium,  Mycobacteriitm smegmatis.
The  masculinization response they
observed (principally the elongation
March
                                                                167

-------
of the anal fin) was nearly identical
to that we observed in a similar
laboratory experiment exposing the
le.'sr killifish to  KME that had also
been microbially degraded.
   Phytosterols in tall (pine) oil can
be microbially  converted to C-19
sterols (Conner  et at. 1976). These
sterols include  steroid compounds
known to  influence sex and repro-
duction. During 1974, for example,
the more than 800,000 tons of tall
oil produced in the United States
could have yielded more than 20,000
tons of phytosterols (Conner et al.
1976). The amount discharged to
the environment cannot  be calcu-
lated, but even a small fraction could
significantly harm  fishes and other
aquatic  organisms.
   Our studies indicate that repro-
ductive systems in  fishes are useful
bioindicators for detection of  sub-
stances that interfere with endocrine
modulated processes. More specifi-
cally,  live-bearing poeciliid  fishes
such as mosquitofish and least killi-
fish may be useful to detect the pres-
ence of endocrine disrupters.
   Poeciliid masculinization by KME
may be due to a few, many, or spe-
cific combinations of endocrine-dis-
rupter compounds  that  mimic or
trigger an organism's receptors to
its own steroidal androgens.  It is
likely  that the  masculinization re-
sponse varies with  exposure  time,
concentration,  degree  of microbial
activity, fish species, and water con-
ditions (e.g., temperature, pH, and
conductivity).

Bioindicators  for the duration
and intensity of KME exposure

The field and  laboratory studies
conducted thus far represent only
short-term observations of the mas-
culinization response to  KME;  the
results may not be indicative of what
one might observe under long-term,
continuous exposure. Rosa-Molinar
and Williams (1984) noted the po-
tential  for diminished fecundity
among arrhenoid mosquitofish that
had been captured from streams re-
ceiving KME. However, most previ-
ous studies have been concerned with
the morphological features of KME-
exposed individuals and have not
considered life-history  traits  that
could  ultimately affect an indivi-
   7 -
   6 -
01
c
o
_J
I   3
    10   12   U   16   18   20
         Stondord Length (mm)
                               22
Figure  3. Scatter diagram of anal-fin
length versus standard length from the
least killifish, indicating the degree of
anal-fin modification relative  to the
point of kraft-mill effluent discharge:
fish  collected immediately below the
discharge point of  kraft-mill effluent
(dark triangles), fish from the farthest
distance downstream (open triangles),
and  fish from mid-distance along the
stream (asterisks).
 dual's fitness.
   Fish life-history traits, including
 the  reproductive characteristics of
 poeciliid fishes, can vary relative to
 environmental conditions  (e.g.,
 Trexler 1988). Therefore, continu-
 ous  exposure to KME might affect
 not  only the sexual characteristics
 of female  fishes  but also their
 offspring's fitness and development.
 Long-term exposure may also have
 an impact  on other population pa-
 rameters such as mortality, growth,
 reproductive rates, and abundance.
 We  strongly  suspect that females
 masculinized by long-term (perhaps
 eight months to a year) exposure to
 water receiving KME suffer from
 impaired reproductive function.
   Studies that have investigated the
 response of fish to continuous KME
 exposure have not reported any overt
 androgenic effects in  other species.
 However, Munkittrick et al. (1992)
 noted testicular atrophy in  males
 and  abnormal oocytes  in the ova-
 rian tissue of females among KME-
 exposed whitefish.  We believe the
 long-term effects of KME exposure
 in fishes will be found  to include
 reduced embryo viability, develop-
 mental modifications, and neuter-
 ing of female reproductive function.
 The effects may include responses to
 other potential KME components
(e.g.,  dioxins, furans, and  chlori-
nated lignins).
  Hermaphroditism  among  KME-
masculinized females appears to he
rare (Bortone and Drysdalc 1981).
However, we may be observing  in-
terscxuality that could evenrunlly
lead toward facultative hermnphro-
ditism.  If fishes exposed  to  KME
have reduced fitness and shortened
life spans, they  may  not  live long
enough to achieve full hermaphro-
ditism. Notably, the observation that
highly masculinized females (as wit-
nessed by the extreme elongation of
the anal fin rays) are rare in our field
collections  might indicate higher
mortality  levels among  modified
fish.
   At present, we have no  way of
measuring the exact amount of KME
oritscomponents presentin a stream
at any given site or time. We have
noted, however, that the  degree of
masculinization  varies  with  differ-
ent conditions. Interestingly, large-
size mosquitofish and least killifish
were generally absent where the most
masculined female fish were found—•
from streams having the highest rela-
tive amount of KME and from sites
proximate to the  KME  discharge
point. However, in streams with rela-
tively  low concentrations of KME,
where poeciliid  fish displayed less
masculinization, the fish were larger.
   During prolonged drought (three
months or more), both mosquitofish
and least killifish were  smaller and
less abundant in streams receiving
KME  than in other streams. The fe-
males exposed  to   KME  during
drought displayed more prominent
anal-fin  elongation compared with
females exposed under other condi-
tions. Drought conditions may con-
centrate the  masculinization factor
present in KME, or the process gen-
erating the masculinizing factor may
be more effective under these condi-
tions.
   The  degree  of masculinization
among female fish (when compared
with normal male behavioral traits)
decreased when fish were captured
from  the field and placed in aquaria
free of  KME. Furthermore, gono-
podial and other morphological fea-
tures showed no  further  develop-
ment. Our unpublished observations
and those of Hunsinger et  al. (1988)
confirm  that  KME-masculinized
 168
                                             BioScience Vol. 44 No. 3

-------
mosquitofish and least killifish can
produce viable offspring after hav-
ing been pluced  in aquaria free  of
KME.  Although Larkin (1986) ob-
served male reproductive  behavior
in female mosquitofish continuing
as long  as  they  were exposed  to
water  containing microbially de-
graded phytosterols, we found that
male reproductive behavior was not
detectable amongKME-masculinized
female mosquitofish after they had
been acclimated for two months to
water lacking KME (Bortone et  al.
1939).
   Assessment of KME effluents  re-
quires long-term  strategies to effec-
tively define and  evaluate effects  on
reproductive cycles and life-history
alterations. To date,  such in-depth
assessments  and evaluations have
not  been conducted. Therefore,  we
are  not  yet able  to definitely state
whether the observed masculiniza-
tion is due  to androgenic or, alter-
natively,  antestrogenic stimuli.
(Antestrogeris are compounds that
inhibit estrogenic processes and ova-
rian function.) We have described
the  effects as an  androgenic  stimu-
lus because we observed production
of embryos in females after removal
from  laboratory exposure to  the
microbially transformed phytoster-
ols and because male juvenile Ameri-
can eels demonstrate accelerated tes-
tes development (Caruso etal. 1988)
at a time in their life history when
sex  determination is not normally
possible (Helfman et al. 1987).
   Also, the hypothesis that mascu-
linization is due  to the presence of
an androgenic stimulus in  paper-
mill effluent  is supported even
though  there  are often  dioxins
present in  the effluent. Dioxins  are
antestrogens. Laboratory simula-
tions using plant phytosterols in  the
absence of dioxins induced mascu-
linized morphological  and behav-
ioral effects comparable to those
observed in the poeciliid species ex-
posed to KME in field studies.
   These poeciliid fishes  are dedi-
cated invertebrate foragers. Piscivo-
rous fish species feeding  at  higher
trophic levels may be more vulner-
able to uptake and accumulation of
halorganics from their prey species.
This masculinization may reflect the
waterborne mode of exposun; con-
trasted with the acquisition of a
c,   3
o>
:§   2
o
<   t
                      ' molt control
                      female control
       I I  I  I I  I  I  I I  I  I  I I  I  I
         30    60    90   120   150
               Age In Days
 Figure 4. Results of continuous expo-
 sure of female mosquitofish to kraft-
 mill effluent (beginning one day after
 birth). The male and female controls
 were fish not exposed to kraft-mill ef-
 fluent. (Redrawn from Drysdale and
 Bortone 1989.)

 halorganic  chemical  body burden
 through the food web.

 Degrees of masculinization as
 a bioindicator

 Until  other methods of  der?'. .ion
 and measurement other  thai; the
 fish's morphological and behavioral
 response per se are developed, one is
 faced  with an  experimental tautol-
 ogy: heavily exposed fishes may be
 so severely modified that the female
 fish appears as a normal  male and,
 therefore, undetectable by gross in-
 spection in  the field. Moreover, fe-
 male  fish may proceed  through a
 complete series of intersexual steps
 in response to continued  androgen
 exposure. This progression may be
 significant if exposure occurs dur-
 ing ontogenetic  development.  It
 could eventually lead to  hermaph-
 roditism. Clearly, both laboratory
 and controlled field exposures are
 needed, the former focusing on KME
 component extraction and the latter
 on  multigeneration  and  long-term
 exposure effects.
   There is additional experimental
 evidence indicating that different
 androgenic compounds produce dif-
 fering degrees of morphological
 modification  among  fish species
 (Asahina et al. 1989), further con-
 founding attempts to predict a fish's
 response to the complex  chemistry
 of KME exposure. Males of the vari-
ous poeciliid species mature at dif-
ferent sizes and age as a genetic  or
adaptive trait (Travis  et al. 1989,
Trexler and Travis 1990), which
further  underscores the need for a
carefully conducted series of obser-
vations  on  fishes exposed to KME.
   Although the mechanisms for sex
determination among fishes are di-
verse (Angus 1989), sex expression
may be adaptive.  Genetically, sex
determination has been described as
polygenic in many  fishes (Kosswig
1964). If the polygenic sex determi-
nation hypothesis  is correct, there
could  exist  multiple, genetically
based and variable, responses to the
exposure  to endocrine disrupters.
Regardless  of whether or  not the
endocrine  disrupters are  acting
through a genetic or environmental
operand, we are alarmed at the po-
tential problems they may cause to
aquatic and other organisms.
   To  date, masculinization  of
poeciliid fish has been considered a
scientific oddity. Concomitantly, its
importance as a bioindicator has
been unappreciated.  Few studies
have elucidated the potentially dis-
ruptive effects of hormones or hor-
monelike  substances on  natural
populations in the field. Gibbs et al.
(1991)  found that populations  of
the  American oyster drill (Urosal-
pinx cinerea) declined when the  fe-
males apparently become masculin-
ized (i.e.Jmposex) when exposed to
tributyltin in nature.
   After the  initial  observations of
arrhenoidy in mosquitofish, we con-
ducted  different bioassays to deter-
mine if an individual had been ex-
posed to KME in the coastal stream
environment. The  bioassays made
use  of  the  morphological  and be-
havioral responses of females ex-
posed to paper-mill effluent (Bortone
et al. 1989). Drysdale and Bortone
(1989) conducted a series of experi-
ments that indicated that the induc-
tion of masculinization can occur
early in the life history of these fishes
(Figure 4).  In another study,  we
noted the relationship between the
degree  of masculinization  among
female mosquitofish to the proxim-
ity of the paper-mill discharge point
(Bortone and Drysdale 1981).
   In the Fenholloway River, poe-
ciliid fishes  are virtually the only
species  present during  times  of
 March  1994
                                                                 169

-------
drought, when  KME is presumably
more concentrated (judging by the
dark-colored water). In a biotic re-
gion where  high  aquatic biodiver-
sity is the norm, this stream is dis-
tinctly depauperate of fish species.
Tributary streams, peripheral pools,
and entering spring runs are rich in
fish  species absent from  the  con-
taminated portions.  Additionally,
the female poeciliids in  these  adja-
cent habitats show  no sign of mas-
culinization.
   Poeciliids have the potential to
serve as indicators of water quality
to determine if and how fishes and
other aquatic organisms (especially
other vertebrates)  are affected by
effluent containing endocrine dis-
rupters. Fishes in  the family Poe-
ciliidae are naturally distributed in
the lowland and coastal areas of the
temperate areas of the New World.
Most species are tolerant  of a wide
range of environmental conditions
and, therefore, are found in a broad
range of habitats.
   The mosquitofish is naturally dis-
tributed in  a variety  of habitats as
well  (Krumhplz 1948), either as its
eastern Atlantic slope form, Gani-
busia affinis holbrooki, or  its Gulf
of Mexico  and Mississippi embay-
ment (orm,Gambusia affinis affinis.
Moreover,  it has been introduced
throughout the world as an ill-con-
ceived aid for mosquito control. Its
abundance, small size, broad distri-
bution, and tolerance of a range of
environmental conditions indicate
that the mosquitofish is an excellent
candidate to serve as a natural sen-
tinel for detecting environmental
stress. It may be  useful at detecting
stress caused by the addition of en-
docrine disrupters to the  aquatic
environment. Moreover, the fish can
be especially  useful when stress
causes  them to react through ob-
servable  changes in  reproduction,
development, and other life-history
features.
   In the future, it is likely that long-
term monitoring of secondary sex
characters and life-history traits in
poeciliid and other fishes will serve
to detect the presence of endocrine
disrupters. The advantage of such a
detection system  is that  it recog-
nizes the ecological impact  these
compounds may cause. Similarly,
the  life-history sentinel may prove
to be a meaningful indicator of stress
owing  to disruption  of  endocrine
modulations in the life cycle of many
organisms.

Application of the model to
other research areas

Endocrine disrupter has emerged as
a generalized term to denote factors
responsible for inducing in the criti-
cal timing of events in ontogenetic
developmental  sequences (Colborn
et al. 1993). These alterations can
affect morphology, physiology, and
life-history traits. This concept has
been brought together in the presen-
tations edited by Colborn and Clem-
ent  (1992) from a  1991  workshop
(called "Chemically Induced Alter-
ations in Sexual  Development: The
Wildlife/Human Connection") held
in Racine, Wisconsin. Participants
in the conference examined various
examples of developmental alter-
ations induced by  environmental
exposure to synthetic compounds.
The focus of the workshop was on
compounds that, after assimilation
by parents,caused transgenerational
exposure to offspring. The second-
generation exposures were often at
dose concentrations much higher
than those typically occurring in the
environment and produced  various
induced morphological or neurologi-
cal modifications, reduced immune
function, and altered reproductive
function  and behavior  among all
classes of vertebrates.
   As more field and laboratory stud-
ies are reported, it is becoming in-
creasingly clear that effects of endo-
crine disrupters are more common
than one might at  first suppose.
Halorganic compounds and plasti-
cisers are among 50  or more  com-
pounds that can induce  similar re-
sponses. Their collective biological
significance has been neglected and,
thus far, notably absent from risk
assessment analysis.
   Fortunately, a considerable  body
of information has recently  become
available on the life history  and ba-
sic biology of poeciliid fishes,  espe-
cially  mosquitofish  (Larkin 1986,
Meffe and  Snelson  1989, Snelson
1989). The potential thus now ex-
ists  for  these  fishes to serve as
bioindicators for some types of en-
docrine  disrupters.  These baseline
data can  serve to help assess the
impact of environmental stress on
the varied life-history features  of
these coastal live-bearing fishes.
   Through  the  efforts  of  Farr
(1989), Travis ct al. (1987), and
Henrich (1988), information exists
on the effectiveness  of several ex-
perimental designs to measure the
impact of environmental factors on
the fitness of these poeciliid fishes.
Moreover, there are  several studies
that have established the normal
behavior  of these fishes and make
effective use of reproductive behav-
ior as a way of assessing the impact
of environmental stress  on  them
(Itzkowitz 1971,  Martin  1975,
Schroder  and  Peters 1988). These
studies on behavioral response, when
coupled with the well-documented
morphological response of live-bear-
ing fishes to environmental stress
(Bortone  et al. 1989, Howell et al.
1980, Okada and Yamashita 1944,
Riehl 1991, and Turner 1960), can
provide reliable endpoint  responses
to potential endocrine disrupters.
   Environmental masculinization of
live-bearing  fishes (including mos-
quitofish, least killifish, and sailfin
mollies) may represent a unique form
of intersexuality. Typically, andro-
gens are aromatized in vertebrates,
resulting in the feminization of males
or antestrogen-induced female dys-
function. Wester et al. (1985)  re-
ported aromatization in the poeciliid
guppy.
   The masculinization of poeciliid
females by androgens in KME repre-
sents only one example of a potent
environmental sentinel among wild-
life species. Concomitantly, it rep-
resents an opportunity to design test-
ing procedures  to evaluate the
general application of the  masculin-
ization bioassay to the detection  of
endocrine-disrupting agents.
   There  is currently strong advo-
cacy  for  initiating  additional tests
to detect potential  endocrine dis-
rupters in the procedures used  to
evaluate pharmaceuticals  and regu-
late chemical discharge. Endocrine
disruption of life  history  has  a
broader significance than traditional
concepts  of birth defects or terato-
genesis. With the potential of trans-
generational exposure and delayed
responses, as in  the impairment  of
immune systems, the effects of these
 170
                                             BioScience Vol. 44 No. 3

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compounds  are particularly  sinis-
ter.
   Synthetically produced chlorinat-
ed  and brominated  organic  com-
pounds  often demonstrate  high
levels of activity as endocrine  dis-
rupters. Perhaps the ability of some
compounds to cause a high level  of
endocrine  disruption  was a  factor
contributing to their original empir-
ical selection as effective pesticides.
Toxicological testing has progressed
from a focus on  acute and chronic
lethal effects to cancer induction on
test species. Literature references of
effects on offspring or adult life his-
tory and  fitness  have not typically
been included in ecological risk-as-
sessment  procedures.  However, re-
productive  toxicology  is rapidly
growing and moving  from the labo-
ratory toward field assessments that
include life-history impact.
   Developing a  well-documented
and  well-referenced system  to rec-
ognize the subtle changes in inter-
sexuality in fishes represents a step
in the right direction to better moni-
tor  the  health  of aquatic ecosys-
tems. It may prevent unpleasant sur-
prises, such as the recent reports of
a global decline in reproductive suc-
cess  among amphibians (Phillips
 1990, Vitt et al.  1990). Fish inter-
sexuality, as a sentinel, may prove a
 reliable bioindicator  to some forms
 of environmental stress.


 Acknowledgments

 We  are grateful  to the  many indi-
 viduals who aided us  with their sage
 advice and counsel on the matters of
 intersexuality and environmental
 stress:  Alani  Davis,  Tom  Denton,
 Dale  Drysdale,  Leroy  Folmar,
 Roxanna  Hinzman,   Mike Howell,
 and  Tibor Kovacs. We  also thank
John Blackie, Shelby Curry, Jenni-
 fer  Kensler,  and  Dan McLeod for
 help in preparing the  manuscript
and  figures.

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