Environmental Health Perspectives Volume
103, Supplement 4, May 1995
[Citation
in PubMed] [Related
Articles]
Possible Mechanisms of Action of Environmental Contaminants on St. Lawrence
Beluga Whales (Delphinapterus leucas)
Sylvain De Guise,1,2 Daniel Martineau,3 Pierre
Béland,2 and Michel Fournier1
1TOXEN, Université du Québec à Montréal,
Montréal, Québec; 2St. Lawrence National Institute
of Ecotoxicology, Montréal, Québec; 3Faculté
de Médecine Vétérinaire, Université de Montréal,
St-Hyacinthe Québec, Canada
Abstract
A small isolated population of beluga whales (Delphinapterus leucas)
that are highly contaminated by pollutants, mostly of industrial origin,
resides in the St. Lawrence estuary, Québec, Canada. Overhunting
in the Þrst half of the century was the probable cause for this population
to dwindle from several thousand animals to the current estimate of 500.
The failure of the population to recover might be due to contamination by
organochlorine compounds, which are known to lead to reproductive failure
and immunosuppression in domestic and laboratory animals and seals. Functional
and morphological changes have been demonstrated in thyroid gland and adrenal
cortex in many species exposed to organochlorinated compounds, including
seals. Morphological lesions, although different, were also found in belugas.
Functional evaluation of thyroid and adrenal glands of contaminated (St.
Lawrence) versus much less contaminated (Arctic) belugas is currently under
way. Necropsy of St. Lawrence belugas showed numerous severe and disseminated
infections with rather mildly pathogenic bacteria, which suggests immunosuppression.
Organochlorine compounds and other contaminants found in beluga whales cause
immunosuppression in a variety of animal species including seals. Thirty-seven
percent of all the tumors reported in cetaceans were observed in St. Lawrence
beluga whales. This could be explained by two different mechanisms: high
exposure to environmental carcinogens and suppression of immunosurveillance
against tumors. Overall, St. Lawrence belugas might well represent the risk
associated with long-term exposure to pollutants present in their environment
and might be a good model to predict health problems that could emerge in
highly exposed human populations over time. -- Environ Health Perspect
103(Suppl 4):00-00 (1995)
Key words: PCBs, organohalogens, beluga whales, cetaceans, reproduction,
endocrinology, immunology, tumors
This paper was presented at the Conference on Environmentally
Induced Alterations in Development: A Focus on Wildlife held 10-12 December
1993 in Racine, Wisconsin.
We acknowledge the logistic support of the Centre Océanographique
de Rimouski and Filmar Inc, as well as the collaboration of A. Lagacé,
C. Girard and M. Morin. Initial funding came from Fisheries and Oceans
Canada and from the Wildlife Toxicology Fund, a joint initiative of World
Wildlife Fund Canada and Environment Canada, with contributions from the
Department of Fisheries and Oceans Canada under the St. Lawrence Action
Plan, from Alcan, the Fondation de la Faune du Québec, Environment
Quebec, and Greenpeace (Canada). Additionnal funding was obtained from
the Canadian Wildlife Health Network, the Canadian Wildlife Foundation,
and patrons of "Let's adopt a beluga." SD was funded by the Fonds
pour la formation de Chercheurs et l'Aide à la Recherche (FCAR)
and is now funded through a Medical Research Council grant.
Address correspondence to Dr. Sylvain De Guise, TOXEN,
Université du Québec à Montréal, C.P. 8888,
Succ. Centre-Ville, Montréal, Québec H3C 3P8. Telephone (514)
987-3448. Fax (514) 987-4647.
Introduction
A small population of beluga whales (Delphinapterus leucas) resides
in the St. Lawrence estuary. From 5000 animals at the beginning of the century
(1), the population has been reduced to approximately 500 (2)
and has been listed as an endangered population (3). After the decline
initiated in the early 20th century by overhunting, several hypotheses have
been put forward to account for the failure of this population to recover
during the last 40 years.
High concentrations of organochlorines, as well as benzo[a]pyrene
(B[a]P) exposure, have been demonstrated in the tissues of these
animals (4,5); the concentrations of polychlorinated biphenyls (PCBs),
dichlorophenyl trichloroethane (DDT), Mirex, mercury, and lead were much
higher than those found in Arctic belugas (6,7).
Postmortem examination of carcasses retrieved from the shores of the
St. Lawrence since 1982 has shown a high prevalence of degenerative, infectious,
hyperplastic, or necrotic lesions often associated with mildly pathogenic
organisms, in addition to a very high prevalence of neoplasms (5,8,9).
The frequency and severity of the lesions described in this population were
considerably higher than what has been found in marine mammals elsewhere.
Consequently, a link was suggested between toxic contaminants in the St.
Lawrence basin food web and the precarious state of the population. The
present article describes the possible relationships between the high levels
of environmental contaminants in St. Lawrence beluga whale tissues and the
various lesions contributing to mortality and to decreased reproduction
in this population, with regard to what is known in other species of marine
mammals, laboratory animals, and humans.
Reproductive System
It is well known that reproductive functions can be altered by the presence
of environmental contaminants, and numerous mechanisms have been proposed,
from the proestrogenic effect of some PCB congeners, to the more subtle
transgenerational effects (10).
In marine mammals, reproductive failure has been suspected in declining
populations of seals inhabiting highly polluted ecosystems, and a link was
proposed between reproductive failure and pollution (11). Uterine
stenoses and occlusions were reported in different populations of seals
in association with high PCB loads (12-14). Premature births in California
sea lions (Zalophus californianus) have also been associated with
high levels of organochlorines (15). Dall's porpoises (Phocoenoides
dalli) from the northwestern North PaciÞc showed reduced testosterone
levels in relation with high PCB and DDE concentrations (16). In
humans, it has been suggested that reduced sperm count could be the result
of exposure to estrogenic pollutants during pregnancy (17). Most
of these associations between reproductive failure and pollution were circumstantial,
but a more recent experimental study demonstrated that seals fed polluted
Þsh showed reduced pup production when compared to those fed much
less polluted Þsh (18).
In St. Lawrence beluga whales, a reduced reproductive rate, possibly
associated with contamination, is suspected because the unexploited population
has not increased in the last 10 years (4,19). Population modelling
indicates that the observed stable population likely results from decreased
reproduction and decreased survival of juveniles (19). Mature spermatozoa
were observed on histological sections of testes of all adult males (De
Guise et al., unpublished observations), but viability, motility, counts,
and the absence or presence of abnormalities, criteria that can be affected
by organochlorines in humans (17,20) could not be assessed. The number
of pregnant females appeared dramatically low in St. Lawrence belugas, and
a quantitative study of the cyclic corpuscules on serial sections of ovaries
demonstrated little ongoing ovarian activity compared to what is reported
in Arctic belugas (21,22). An adult hermaphrodite beluga was found
with two ovaries, two testes, and complete genital tracts of both sexes
with the exception of cervix, vagina, and vulva (23). This was only
the fourth mammal ever reported with two separate gonads of each sex (23).
In view of the multiple developmental effects of pollutants with estrogenic
activity (10), this phenomenon may be related to pollution.
Endocrine System
Thyroid
The thyroid gland appears to be a rather well-deÞned target of
PCB exposure. Altered levels of circulating thyroid hormones (24)
and morphological changes in the thyroid gland (25) have been demonstrated
in rats exposed to PCBs. Histological lesions (colloid depletion and interstitial
Þbrosis) were also found in thyroid glands of harbor seals (Phoca
vitulina) in the North Sea during the phocine distemper epizootics and
in harbor porpoises (Phocoena phocoena) from the same waters. Both
of these species were contaminated with high concentrations of PCBs, as
compared to the less contaminated harbor seals from Iceland (26).
In another study, harbor seals fed PCB-contaminated Þsh from the Wadden
Sea had decreased concentrations of plasma retinol (vitamin A) and thyroid
hormones when compared to seals fed Þsh from the Atlantic (low levels
of PCBs) (27). No clear evidence of thyroid changes similar to those
described in seals and porpoises were found in St. Lawrence belugas. It
should be noted that subtle differences should be interpreted with care
because seasonal variations have been demonstrated in thyroid morphology
and secretion in Arctic beluga whales (28). However, other lesions
were found in St. Lawrence animals including abscesses in the thyroid, an
uncommon Þnding in other species, and two small thyroid adenomas in
one animal. The circulating levels of thyroid hormones and vitamin A of
highly contaminated St. Lawrence belugas are currently being compared to
much less contaminated Arctic belugas that have already been sampled and
analyzed.
Adrenals
Adrenal glands are also affected by organochlorines in some laboratory
animals. Bergman and Olsson (29) reported adrenal hyperplasia in
grey seals (Halichoerus grypus) and ringed seals (Phoca hispida)
in the Baltic Sea, which they associated with the high loads of organochlorine
pollutants observed in these populations. More recently, abnormally high
concentrations of organochlorines were demonstrated in adrenals of rodents,
birds, and seals, and metabolites were found to bind covalently to adrenal
cortex cells where their toxicity was expressed (30). These binding
and toxic characteristics varied in different species (30).
Two types of lesions affected the adrenal cortex of St. Lawrence belugas:
hyperplastic nodules and serous cysts (9). Morphologically, the nodules
appear as intermediate between hyperplastic foci and adenomas, according
to the classiÞcation criteria used for domestic animals, rats, and
humans (31-33). However, such a high incidence of adenomas in a single
population would appear unusual. Whether these nodules are functional or
not is still unknown. Serous cysts have apparently never been described
in domestic animals, but similar lesions were reported in female white-sided
dolphins (Lagenorhynchus acutus) (34). These lesions presumably
reflect a functional alteration of the physiology of the adrenal cortex.
The pathophysiology proposed for the development of cysts in the adrenal
cortex of beluga whales (9) involving hydropic degeneration of clusters
of adrenocortical cells, could correspond to an exaggeration of the adrenocorticolytic
process as described under DDT metabolite exposure (30). Circulating
levels of corticosteroids in highly contaminated St. Lawrence belugas, compared
to much less contaminated Arctic belugas, are currently being investigated
in the course of a study on immunotoxicology. An investigation is planned
to determine the presence of DDT metabolites in adrenal glands and the presence
of any potentially adrenocorticolytic compound in the blubber (reflecting
exposure) of St. Lawrence belugas.
Immune Functions
Ample evidence that organohalogens have detrimental effects on the immune
system of man and animals has been collected over the past two decades.
These compounds alter the functions of both arms of the immune system, cellular
and humoral immunity. 2,3,7,8,-Tetrachlorodibenzo-p-dioxin (TCDD),
the most immunotoxic of aromatic halogenated hydrocarbons, induces thymic
atrophy in most experimental species (35-38). PCBs, and most notably
the coplanar congeners, have similar, albeit less severe, effects; they
cause lymphoid depletion in chicks (35), reduce natural cell toxicity
in rats (39,40), decrease the number of T cells and the T helper/T
suppressor cell ratio in nonhuman primates (41), and reduce T cell-mediated
cytotoxic activity in mice (37). PCBs decrease antibody production
in response to injection of sheep red blood cells (SRBC) in PCB-treated
mice and nonhuman primates (41-43). A reduction of serum IgA levels
seems to be a consistent component of PCB immunotoxicity (42,44,45).
B cells and particularly B cell differentiation are emerging as important
targets for halogenated hydrocarbons (36). Serum corticosteroid levels
are also altered by PCBs (37,46,47). The immunotoxicity of various
metabolites of PCBs has also been demonstrated; chlorinated diphenyl ethers,
found in Great Lakes Þsh, signiÞcantly decrease circulating
lymphocytes in male rats (48).
It is not surprising that PCB-induced immunosuppression results in a
higher sensitivity of experimental animals to a wide variety of infectious
agents: gram-negative bacteria (or their endotoxins), protozoa, and viruses.
The sensitivity of PCB-treated mice to endotoxin, malaria (44), and
bacteria (43) is increased; rabbits synthesize less antibodies after
being challenged by pseudorabies virus (49), and mice are more sensitive
to challenge by Herpes simplex and ectromelia (mousepox) (50); the
resistance of PCB-treated ducks to duck hepatitis virus is also impaired
(51). Similarly, the complement system, a nonspeciÞc defense
mechanism against infectious agents, is altered by PCBs (52).
Studies on other pesticides conÞrm this xenobiotic-related immunosuppression
of humoral and cellular responses as well as the decrease in natural resistance
to viral and bacterial infections (53-55). Immune humoral (53,54,56,57)
and cellular (58,59) responses to dieldrin, one of the most potent
immunosuppressive insecticides (53), were examined after intoxication
of inbred mouse strains with different natural resistance to selected pesticides.
The data showed that single sublethal doses of dieldrin inhibited the number
of SRBC-primed cells (53,57). Similar patterns of dieldrin-induced
immunosuppression of the primary IgM response to thymodependent and T cell-independent
antigens were observed, suggesting a dysfunction of cellular cooperation
during the induction phase of the immune response (57). Exposure
to single sublethal doses of dieldrin, however, resulted in transient inhibition
only of mixed lymphocyte reactivity (MLR) and in abrogation of graft-versus-host
reaction at a time of maximal MLR inhibition, but in no other visible damage
of T cell functions or cell viability (58,59).
The immunotoxic potential of dieldrin was clearly shown in in vivo
models of viral infection with mouse hepatitis virus (MHV3) (53,54,56,60)
and of bacterial infection with Salmonella typhimurium (61).
Decreased macrophage phagocytic (54) and bactericidal (62)
activities were observed following single, sublethal exposures to dieldrin,
and impairment of macrophage antigen processing by dieldrin was observed
in a model of antigen processing (avidin) by the cells (55). These
data showed that exposure to pesticides can affect immune defense mechanisms
and, to some extent, the natural antiviral and antibacterial resistance
of the host.
Recently, seals experimentally fed polluted Þsh from the Baltic
Sea demonstrated suppression of immune functions when compared to seals
fed clean Þsh from the Atlantic Ocean (63). This was the Þrst
experimental demonstration in semiÞeld conditions of effects of a
mixture of contaminants at levels encountered in the environment on immune
functions of marine mammals. The frequent infections with mildly pathogenic
bacteria found in St. Lawrence belugas strongly suggest immunosuppression
that could be related to the high concentrations of environmental contaminants
found in their tissues. A study to correlate an eventual immunosuppression
of beluga whales to levels of contamination in St. Lawrence versus Arctic
animals is currently under way (64,65).
Tumors
Overall, worldwide a total of 75 tumors have been reported in cetaceans;
28 (37%) come from 18 animals out of 45 necropsies of St. Lawrence beluga
whales that were collected since 1982 from a population of only around 500
animals (40% of the animals had at least one tumor) (8). Excluding
gastric papillomas that were attributed to papillomaviruses (66),
the cause of the tumors observed in St. Lawrence belugas is unknown. Two
factors could have contributed to such a high prevalence of neoplasms in
that single population: exposure to carcinogenic compounds and decreased
resistance to the development of tumors.
Thoughout their lives, St. Lawrence belugas are exposed to various toxic
compounds, some of which are well known carcinogens. B[a]P, to which
St. Lawrence whales are exposed (5,67), is among the more potent
genotoxic carcinogens found commonly in contaminated environments, acting
as an initiator (68,69). Others, such as PCBs, are recognized as
promoters of tumors in initiated cells (68). Numerous compounds that
are not directly carcinogenic can induce hyperplasia, which was recently
pointed out as an important event in carcinogenesis (70). Preconception
exposure of parental germinal cells or exposure of fetal somatic cells in
utero to chemicals that would provide the Þrst step in carcinogenesis
(known as initiation), followed by postnatal exposure to tumor promoters,
would result in increased incidence of tumors, with possible transgenerational
effects of carcinogens (71). This feature of chemical carcinogenesis
should be investigated as a possible contributing factor to the high prevalence
of neoplasms in St. Lawrence belugas. Should transgenerational effects be
involved, the prevalence of tumors could stay high for a long period of
time because high burdens of lipophilic pollutants are carried by females
and transferred to offspring through the placenta and milk in this species
(De Guise et al., unpublished data) (4).
Decreased resistance to the development of tumors could also be an important
contributing factor. Higher prevalence of lymphoreticular, DNA virus-induced,
and chemical carcinogen-induced neoplasms was found in nonspeciÞcally
immunodeÞcient hosts (68,72,73), athymic mice (nude mice),
and beige mice, respectively, demonstrating the role of the immune system
as a whole, and of T lymphocytes and Natural Killer (NK) cells in immune
surveillance for tumors. NK activity, among others, may be influenced by
a variety of factors (8), some of which may be speciÞcally
influenced by contaminants found in the tissues of belugas. For example,
concentrations of estrogens and vitamin A and its precursors, which can
be altered by PCBs and DDT (74), may in turn influence NK activity
(75-77). In addition, PCBs are direct immunosuppressors (78).
Conclusion
High concentrations of a complex mixture of ubiquitous pollutants were
found in tissues of St. Lawrence beluga whales. Among these chemicals, many
were demonstrated to have adverse effects on different aspects of the normal
physiology of various species of animals, most often in laboratory animals.
Many of the effects demonstrated experimentally were also observed in other
highly exposed species of animals and humans in their own environments where
cause-effect links were strongly suspected. The highly exposed St. Lawrence
beluga whales also exhibited lesions in most of the target systems identiÞed
in toxicological studies of other species of marine and land mammals, as
well as humans. This long-lived (30 years) species appears to reflect particularly
well the risks associated with life in a polluted ecosystem. We propose
it as a model for potential long-term consequences of pollution on human
health.
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