Life Sciences International Research Journal Volume 6 Issue 1 ISSN 2347- 8691

AN OVERVIEW OF THE EFFECTS OF

ENDOCRINE DISRUPTERS (EDCS) IN FISH
Bhawna Srivastava
Asst.Professor, Department of Zoology, DAV College, Kanpur, U.P, India
Dr. Reddy P.B
Department of Zoology, Government PG College, Ratlam, M.P, India
reddysirr@gmail.com

Received: May 2019 Accepted: Jun. 2019 Published: Nov. 2019

Abstract: The present review attempts to explore a critical assessment on the effects of EDCs on
physiology and health status in fish. Most of the earlier assessments were mainly engaged on defining
peripheral adverse effects as endpoints rather than discovering the mechanism(s) responsible for
observed effects. For the present investigation, an online search was conducted from various scientific
databases to obtain the relevant data.
Results of the published literature reveal that EDCs have the capability to mimic endogenous hormones,
and may inversely affect male or female reproductive physiology. Reduction in the gametes number,
development of intersex gonads, changes in the gonadosomatic index, gamete viability and reduced
fertility rate has been frequently acknowledged. Variations in sperm density, motility, and fertility in
males and inhibition of oocyte growth and maturation and the incidence of apoptotic/autophagic
processes in female species have been reported. Certain EDCs can act also at gene level producing DNA
mutations and changes in epigenetic pathways. In conclusion, the present review sum up that EDC
exposure affects reproduction, disruption of steroidogenesis, feminization effects, distorted behavior
patterns, response to stress, and incidence of epigenetic process, impact on thyroid and immune system
focusing on mainly reproductive impairment in fish species. Therefore, for effective regulation, a set of
global standardized and sensitive toxicity tests are to be established to ensure further description of
EDCs properties.

Keywords: Aquatic Pollution, EDCs, Endocrine Disruption, Fish Reproduction.

Introduction: The occurrences of recently acknowledged contaminants so-called “endocrine disrupting

chemicals (EDCs) in our aquatic environments are of continued and is a global burning concern. These
Endocrine disrupting chemicals (EDCs) enter the aquatic environments through industrial and urban
discharged effluent and affect the metabolism and reproductive physiology of aquatic species, including
fish. All vertebrate animals, from fish to mammals keep fundamentally the same hormonal mechanisms
for dealing with the pollutant exposure. Hence, impacts of EDCs on fish can be projected in a large
range of other animals including humans. Both wildlife and human offspring are currently exposed to a
variety of synthetic chemicals at above the environmentally relevant concentrations, which have proven
to be hazardous for normal embryonic development [1]. The presence of certain natural and synthetic
chemical compounds in the aquatic environment can disrupt endocrine systems, leading to the
reproductive destruction and threatening the survival of wild populations. A number of wildlife
populations have been affected by endocrine disruption by various endocrine disrupting chemicals
(EDCs) which primarily shown negative effects on growth and reproduction [2].

Endocrine disrupting chemicals (EDCs) are discharged into environment from packaging industries,
pesticides, urban wastes and food constituents. Scientific evidences, laboratory experiments, and
epidemiological studies suggest that EDCs can provoke major risks for human being by targeting
different organs and systems in the body. Several molecular pathways through estrogen receptors,
nuclear receptors and steroidal receptors activation are involved in targeting the normal system [3].
Animals populations exposed to various environmental pollutants are exhibiting strong evidence of

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hereditary defects and reproductive anomalies. It is also evident that certain chemical substances
interfere with steroidogenesis and the physical development of embryo [4].

Evidences of endocrine disruption in wild population through food chain have been well-documented
[5], [6]. Evidences are also available that humans have behavioral disorders similar to those observed in
wild populations [3], [7], [8], [9]. Therefore, pollutants with endocrine disruptant properties are now
subject to definite regulatory action in various authorities such as the European Union and the United
States [10], [11]. Fresh and novel testing methods exclusively developed to identify and evaluate potential
endocrine disrupting chemicals (EDCs) are available from the Organisation for Economic Cooperation
and Development (OECD) (OECD, 2016).Most studies looking at endocrine-mediated effects are usually
carried out in mammals. Nevertheless, in ecotoxicological experiments fish and amphibian species are
still scanty [2]. (Matthiessen, P et al, 2018).

Evidences are now mounting up that even low levels of contaminants can disrupt the normal
functioning of the endocrine system of fish [12]. Fish species can serve as biomarkers of aquatic pollution
due to their comparatively large sizes, long survival and their various trophic levels [13], [14], [15], [16]. A
few of the defects found in fish, including reduced fecundity, genital anomalies, distorted behavior
patterns, reduction in immunity and response to stress and disease [17]. Though fish have some major
differences in their endocrine system compared to that of mammals, their fundamental basis is very
similar. Therefore, pollutants that are or suspected to be endocrine disruptors in fish can absolutely be
measured as potential endocrine disruptors. Due to their high nutritional value, human beings consume
fish extensively. Ingestion of fish polluted by EDCs might escalate health risks for human beings [18]. For
that reason, it was very important to determinate and to investigate the effects of EDC in fish species.

Materials and Methods: For the present investigation, online search was conducted to obtain the
relevant data. The data was acquired from various scientific databases like PubMed, Research Gate,
Google Scholar, ClinicalTrials.gov and endocrine societies. The search phrases were “various types of
EDCs” “endocrine disrupting chemicals and fish health”, “reproductive system and EDC”, “thyroid
system and endocrine disruption”, “EDC and aquatic environment”, “EDC and oxidative stress” and
endocrine toxicants”, and “carcinogenicity and danger of EDC”. The studies of experimental animal
models were also examined for additional research and their applicability when exposed to EDC. Effects
of EDCs in relation to metabolism, physiology, organs and sources of exposure have been studied. The
complete understanding of this assessment will give us new direction to the future and guidance in
endocrinology related toxicology.

Results and Discussion: Feminization of Fish: There is an escalating concern about the presence of
various synthetic chemicals in the aquatic environment that mimic estrogens to disrupt the
reproductive function. Release of urban and industrial wastewater upholds the entry of varied
oestrogenic chemicals into the water bodies. This complex mixture of EDCs obstructs in the
steroidogenic pathway and supports severe reproductive impairment in freshwater fish
populations. Fish are most suitable indicator species for feminization effects as male species are more
susceptible than humans to xenobiotic estrogenic compounds. Feminization in fish and other aquatic
vertebrates has been thoroughly studied since it was first revealed in the 1980 s in male rainbow trout
(Oncorhynchus mykiss) due to sewage exposure triggered great concern about the estrogenic
contamination[19], [20], [21]. [22], [23], [24]. [25], [26]. They used plasma VTG in males as a key
biomarker in these studies. In contrast to females, the male fish are not capable to convert VTG into the
yolk protein and consequently, VTG can accumulate in the blood plasma. It has been confirmed that the
synthesis of VTG in male fish may cause kidney damage [27] and may reduce metabolic outflow for
growth and spermatogenesis [28]. However, in female fish, an abnormal increased level of VTG has been
linked with decreased estradiol synthesis [29], which in turn may harmfully influence egg quality.
Stimulation of VTG synthesis in female fathead minnows (Pimephales promelas) exposed to E2-17D and
E2 has been linked with reduced egg production [30], [31]. The epidemiological data sets have confirmed
that the incidence of feminized fish is associated with effluent discharges and that the frequency and
severity is positively correlated with the proportion of treated sewage effluent in receiving waters [32].

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Jarque, S., et al [33] have examined the expression of estrogen-regulated genes in male fish from the
most distant environments of high mountain lakes, and found incipient feminization involving
expression of estrogen receptor and zona radiata genes. They correlated this effect with the
concentrations of some organochlorine compounds in fish and were consistent with the continual
occurrence of these pollutants in the most remote planet regions. Municipal wastewaters have been
known to contain a variety of EDCs. Huang, G.Y et al [23] have investigated the estrogenic and/or
androgenic effects in wild mosquito fish (Gambusia affinis) in two polluted rivers of South China.
They found significant induction of Vtg and ERα mRNA in the livers of the males and a gonopodium-
like anal fin in the females collected at the polluted sites of the river, which indicate that the EDCs
present in the two polluted rivers, could cause the observed estrogenic and androgenic effects in
mosquito fish. A recent study of Weber, A.A.et al [25] indicate that the urbanization and subsequent
discharge of municipal wastewater containing oestrogenic compounds in the aquatic environment are
altering the levels of sex hormones and gametogenesis of Astyanax rivularis.

Based on appraisal of the accessible data, it is concluded that the weight of evidence for endocrine
disruption in fish is adequate to develop a risk management approaches for EDCs that discharge to the
aquatic environment.

Impaired Stress Response in Fish: Natural or synthetic chemicals present in the aquatic environment
can affect the ability of the fish to respond appropriately to the stressors [34]. Interference of EDCs with
the normal function of the stress axis can rationally be predictable to have adverse consequences for the
individual. Intervention of EDCs with the normal function of the stress axis in fish, and vertebrates is of
great concern for many reasons. The neuroendocrine stress response is a major module that helps in
survival of the fish during critical periods of the life cycle. The presence of chemicals in the aquatic
environment may interfere with the hormone function of animals. Fish and other aquatic animals are
usually encountered with a variety of physical and chemical stressors. Nevertheless, only few studies
have addressed stress as a potential but challenging factor for bioassays that use fish as test organism.
Certain stress responses are measureable through gross or microscopic examination of various organs or
tissues.

Fish responses to stress can be categorized into primary, secondary, and tertiary phases [35]. The
primary phase is comprehensive neuroendocrine response in which catecholamines (epinephrine and
norepinephrine) and cortisol are released from the adrenal gland. Greater levels of these hormones
trigger a secondary response that involves physiologic and metabolic pathways (hyperglycemia,
vasodilation of arteries increased cardiac stroke volume, and immune function depression [36]. These
two phases are thought to be adaptive and enable the fish to adjust to stressors and maintain
homeostasis. Nevertheless, the third responses involve systemic changes in which organism becomes
unable to adapt to the stressors and that leads to initiate adverse effects on the overall animals’ health
(growth, reproduction, disease resistance, and behavior [35].

The stress response in fish and other vertebrates is facilitated by the hypothalamus-pituitary-inter-
renal/adrenal (HPI/A) axis [36]. In brief, stressors (EDCs) initiate synthesis of corticotrophin-releasing
hormone by the hypothalamus, which in turn stimulates release of adrenocorticotropic hormone
(ACTH) by the pituitary. The ACTH then stimulates the head kidney to produce the active hormone
cortisol (fish) or corticosterone (higher vertebrates) which together with catecholamines (adrenalin)aids
the animal handle the stress by prompting a set of changes including stimulation of heart rate, glucose
mobilization, fat metabolism and osmoregulation [34]. Hontela [38] found inter-renal dysfunction,
endocrine impairment and reduced plasma cortisol levels in fish yellow perch (Perca flavescens) and in
northern pike (Esox lucius) sampled at sites polluted by cocktail of contaminants. The reduced
capability to react to ACTH point out that the normal neuroendocrine response to stressors (EDCs)
perhaps disrupted and that the competency to cope stressors in the aquatic environment may be
significantly reduced in the affected animals. Norris, D.O., et al (1999) [39] found a weakened
adrenocortical response to stress in brown trout, Salmo trutta, living in metal-contaminated waters of
the Eagle River, Colorado. The outcome of this study suggest that short-term detention stress by the

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hypothalamo–pituitary–adrenocortical axis of chronically exposed fish was depressed and fish could not
tolerate the stress response as readily as control fish.
Pottinger, T.G., and Matthiessen, P [34] have shown that the fish Gasterosteus aculeatus) living at the
contaminated in rivers in the northwest of England, release higher quantities of the stress hormone
(cortisol) into their blood than fish from the reference site. He found that, the stress response is
increased up to three times the normal level of cortisol of the fish of contaminated site. The study of
Mehdi, H., et al [40] clearly proves that chronic exposure to WWTP effluent on energetics, stress
response of rainbow darter (Etheostoma caeruleum) affects whole-body metabolic performance, and
found that sex-differences are a key determinant of various metabolic changes in response
to physiological stress. Recently, Lee, J.W., et al [41] evaluated the pharmaceutical drug (metformin)
aquatic toxicity in Oryzias latipes under a multi-generational exposure schedule. They found occurrence
of intersex in F0 generation, increased the reactive oxygen species (ROS) and decreased the glutathione
(GSH) content in F0 male fish compared with those of the control. The results confirmed that exposure
to pharmaceuticals (metformin) lead to oxidative stress and two-generation endocrine disruption in O.
latipes.

Reproductive Impairment: Aquatic environments have become pools for the cocktail pollutants. The
results of ongoing laboratory research raised a concern about the potential hazards of endocrine-
disrupting chemicals in the aquatic environment. In recent times, the data on the effects of Endocrine
disrupting chemicals (EDCs) on fish reproduction, focusing on the deregulation of the hypothalamus -
pituitary-gonadal axis as well as on gamete quality, was significantly increased. Depending on their
capability to mimic endogenous hormones, they may affect differently in male or female reproductive
physiology. Inhibition of gametogenesis, development of intersex gonads, alteration of the
gonadosomatic index, and alterations of sperm density, motility and decreased fertility rate has been
largely documented [42].

Thomas, P., et al [43] shown that chronic environmental exposure and hypoxia caused clear suppression
of ovarian and testicular growth along with endocrine disruption in Micropogonias undulate. Devaux,
A., et al [44] discovered the association between the integrity of sperm DNA and the quality of offspring
as a possible cause of the decline of a feral fish (Chondrostoma nasus) population. They found sperm
DNA damage, in the fish living in contaminated water. Bhandari et al [45] found noticeable reproductive
abnormalities in Japanese medaka for the first two generations of fish exposed to BPA for one week and
continued the experiment for four generations. They also found a reduced rate of fertilization and
increased embryo mortality in future generations. Yu, L., et al [46] performed long‐term exposure to low
concentrations of polybrominated diphenyl ethers (PBDEs) on zebrafish (Danio rerio) over 2 generations
and confirmed that PBDEs in zebrafish could cause reproductive impairment, and might have
considerable adverse effects on fish population.

Roy, R.Y., et al [47] investigated the effects of EDCs on immune suppression, reproductive impairment
(estrogen responsive gene expression, fecundity, fertilization success, hatching success, and
reproductive competence index) in marine medaka Oryzias melastigma). The findings in marine
medaka reveal distinct sex differences in the EDCs mediated biological responses. In contrast, Brain,
R.A., et al [48] could not found any significant alterations in atrazine exposed fathead minnow
(Pimephales promelas) and Japanese medaka (Oryzias latipes) at environmentally relevant
concentrations.

The results of Wang, Q., et al [49] revealed that that BPA (EDC) disrupts testis maturation
through apoptosis of germ cells and Leydig cells, inducing a decrease in 11-KT levels to
disrupt spermatogenesis. Overall, the results provide insights into the molecular and cellular
mechanisms of BPA induced reproductive impairment in goldfish (Carassius auratus). Similar results
were also found in H.fossilis exposed to BPA [50].

Thyroid Disruption in Fish: Thyroid hormones are involved in many metabolic and physiological
(growth, development, behaviour, stress) processes. There is considerable confirmation that

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polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that
environmentally occurring doses affect thyroid homeostasis [51]. The thyroid function in fish is
intermediated through the hypothalamo-pituitary-thyroid (HPT) axis and molecular mechanisms of the
HPT axis in this group resemble closely to those of mammals [52]. The complexity of this system
possibly permits EDCs to effect at many points, including on hormone synthesis, transportation, and
peripheral stimulation [53]. Most of the contaminants include PCBs, (polychlorinated dibenzo dioxins)
DDT, chlorinated pesticides, and PBDEs (polybrominated diphenyl ethers) have been involved in
damage to the thyroid function [51]. Published literature clearly reveal that organic contaminants, heavy
metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may
alter HPT activity, development, and reproduction in fish and in other vertebrates. Out of many, one
example clearly reveal the involvement of PCB in the reductions of plasma T4 and perturbations in
T3/T4 ratios in fish Cymatogaster aggregata and Leptocottus armatus) of San Francisco Bay, USA [54],
[55]. Picard-Aitken, M., [56] reported delayed sexual maturation and thyroid disruption in female
walleye (Sander vitreus) exposed to contaminants in the Ottawa River. Li, D. and Wang, X., [57] found
disruption of thyroid endocrine and expression genes through hypothalamic-pituitary-thyroid axis
(HPT) in zebrafish exposed to BDE-(Polybrominated diphenyl ethers.

Von Hippel, F.A., et al [58] investigated PCB profiles and biological effects in freshwater fish, Alaska
blackfish (Dallia pectoralis) and nine spine stickleback (Pungitius pungitius) living upstream and
downstream of St. Lawrence Island. Fish of downstream exposed to estrogenic contaminants, shown
hypothyroid and presence of vitellogenin. It also exhibited altered DNA methylation in gonads and
altered gene expression, response to DNA damage, and cell signaling. Recently Wang, X., et al [59]
shown alterations in gene transcription, thyroid disruption and hypothalamic-pituitary-thyroid (HPT)
axis in zebrafish embryos treated with decabromodiphenyl ethane (DBDPE). The results of Revathy, V.
and Chitra, K.C., [60] shown that exposure to phthalate plasticizers can disrupt the hypothalamic-
pituitary-thyroid axis (HPT) and abnormal reproductive functions along with thyroid disruption in
Oreochromis mossambicus. Another recent study of Ortiz-Delgado, J.B. [61] confirmed that the
organophosphate pesticide malathion possess the ability to distress integrity of thyroidal tissue and can
alter the normal functioning through HPT axis in Senegalese sole, Solea senegalensis.

Impact on Immune System: EDCs are acknowledged as immunomodulators of in mammals and

teleosts, regulating both the inborn and acquired immune system responses [62]. Fish immunity may
represent a useful predictor of contamination with endocrine disruptors. However, very, little is known
about the immunotoxicological consequences and mechanisms through which these effects are
mediated by EDCs exposure in fish.

Earlier studies mainly focused on the effects of EDCs on the mammalian immune system is focally
affected by EDCs but effects on the immune system in fish have received limited attention only [62]. The
study of Gale et al [63] indicates that xenoestrogens can interfere with estrogen signaling and interact
with estrogen-binding proteins (SHBG) or receptors (ER). Estrogens-EDCs induced Immunomodulation
in teleost fish is of abundant importance due to the witnessed global continuing decrease in aquatic
environments. Endocrine disruption by synthetic chemicals in the aquatic environment has been
documented as an important ecotoxicological threat in the aquatic environment. Most of the earlier
research on the impact of endocrine disrupting compounds (EDCs) on biota has concentrated on
anomalies of the reproductive system. However, there is growing evidence that EDCs can also affect a
variety of physiological systems including the immune system of fish as estrogen receptors are expressed
in immune organs of the fish [64], [65]. It is widely known that EDCs affect all features like
humoral/cellular and innate/acquired immunity of the immune system [64].

Understanding of fish immunity modulation is difficult because several factors can influence both
immune status and the toxic response. Inherent factors such as species, sex, age, and state of maturity
are known to modify the reaction to EDCs and are factors of immune function [62], [66]. Exposure to
higher levels of 17-estradiol (E2) could alter mechanisms of the immune system, prompting
immunosuppressive effects and more disease vulnerability in rainbow trout, Oncorhynchus mykiss[67].

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Xenoestrogens have extensive allegations for immunotoxicity in natural fish populations inhabiting in
contaminated aquatic environments. They can modulate many tasks of immune system in teleosts fish
via ER-mediated pathways. Yet, future research on the immunological effects of estrogens and
xenoestrogens (EDCs) will help to explain the implication of natural exposures in aquatic environments
produced by urban and industrial activities. This conclusion should, of course, be accompanied by a
need for continued monitoring and research on these issues.

Conclusions: In the end, indicating effects of endocrine disruption at the population level is important.
Scientists consider that opportunities exist to apply contemporary molecular techniques to identify the
significant impacts of EDCs on fish populations. Even though research in under controlled conditions in
the laboratory are useful for providing dose-response interactions and establishing underlying molecular
mechanisms but these controlled environs do not reflect the actual exposure conditions in the
environment. Several theories are available to explain molecular interactions of xenobiotics with the
endocrine system. These impacts on the endocrine system may change the productiveness of wildlife
and human beings. In order to care for aquatic wildlife and drinking water resources, the advancement
of methods for detection of EDCs effects on wildlife is required.

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