ReviewDetrimental Effects of Bisphenol Compounds on Physiology and Reproduction in Fish: A Literature Review
Introduction
Endocrine disrupting chemicals (EDCs) interfere with any aspect of hormone synthesis and action. These compounds have the affinity to bind with the hormone receptors and have the potential to incite or suppress the hormone synthesis /metabolism or their action. EDCs can bind to a variety of receptors including nuclear receptors, non-nuclear steroid and non-steroid receptors (receptors of neurotransmitters e.g. dopamine, serotonin, norepinephrine, etc.) and orphan receptors like aryl hydrocarbon receptor (Diamanti-Kandarakis et al., 2009; Goksøyr, 2006; Segner et al., 2003). EDCs not only act through hormone receptors but also exert their effect through epigenetic mechanisms by altering the expression of key genes involved in reproduction and normal development (Bhandari et al., 2015b).
One of the most studied EDCs is bisphenol A (BPA, 4,4'-isopropylidene diphenol, CAS No. 80-05-7). BPA is a commercially important and highly produced chemical around the globe (Cantonwine et al., 2013). BPA was synthesized for the first time in 1891 by condensation of phenol and acetone (Vandenberg et al., 2007) and in 1952 the first plastic product was made with BPA (Vom Saal and Welshons, 2006). Because of its cross-linking properties it is an effective plasticizer (Alonso-Magdalena et al., 2006). Approximately around 90% of the total manufactured BPA is used for the production of plastic and plastic derived products including food and beverage containers, water and baby bottles, toys, impact-resistant eyeglass lenses, helmets and compact discs (Eladak et al., 2015). BPA is also used as an antioxidant and stabilizer during the manufacture of polyvinyl chloride (Staples et al., 1998). Other uses of BPA are in dental sealants as dimethacrylate (BIS-DMA), thermal paper (Biedermann et al., 2010; Mendum et al., 2011) and medical equipment (Testai et al., 2016). The first source of BPA exposure is through plastic and plastic made products while the second-largest source of BPA exposure is through thermal paper receipts (Sogorb et al., 2019) and according to “Regulation concerning the Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH)” BPA will no longer be used in the thermal paper after 2020 (Wang et al., 2018a,b).
BPA has been listed as a class 1B reproductive toxicant by European CLP regulation (Sogorb et al., 2019). A significant correlation was observed in serum BPA levels and patients with dilated cardiomyopathy (Xiong et al., 2015) and polycystic ovary syndrome (Hossein Rashidi et al., 2017; Kandaraki et al., 2011). Recent evidence suggests that BPA also acts as a metabolic disrupting chemical, affecting organs such as the pancreas and adipose tissue (Rahmani et al., 2018) as well as causing metabolic syndromes, such as obesity (Santangeli et al., 2018). Given BPA has many negative physiological and behavioral health outcomes, many countries have now banned BPA in consumer products, especially baby bottles (Li et al., 2016). This led to the use of alternatives to BPA in plastic production. The available alternatives are listed in Table 1. The structure of these BPA analogs is similar to parent molecule (Fig. 1).
Section snippets
Detected levels of BPA and its analogs in the water
In the late 1990s researchers started reporting the detection and quantification of bisphenol-A in surface water (Corrales et al., 2015) after the methods were developed to measure them in the select specialized laboratories. Since then, BPA has been detected in various environmental samples, and the findings suggest the ubiquitous nature of its distribution (Bhandari et al., 2015a).
BPA has been detected in surface water samples collected from Sinos River basin, Rio, Brazil (n.d to 517 ng/L) (
Mechanism of action
Bisphenol-A has become a chemical of highest concern because it can bind with estrogen receptors. BPA has an affinity for nuclear estrogen receptors (α and β), but also the transmembrane G protein-coupled estrogen receptor (tGPR30) (Eckstrum et al., 2016) and orphan nuclear estrogen receptor-γ (ERRγ) (Bulayeva and Watson, 2004; Gould et al., 1998; Matsushima et al., 2007). BPA not only interacts with estrogen receptors but also with androgen receptors and thyroid receptors (Reif et al., 2010).
Effect of BPA and analogs on neuroendocrine system
In fish, reproduction is controlled by a conserved endocrine pathway which includes, pineal, hypothalamus, pituitary and gonads. The neurosecretory system controlling reproduction involves gonadotropin-releasing hormone (GnRH) secreting neurons that secrets GnRH, the primary regulator of reproduction (Millar et al., 2004). GnRH, a decapeptide hormone, synthesized by the hypothalamus which receives the environmental signals through the pineal gland and secrets GnRH to initiate the hormonal
Effect on Reproduction
Reproduction in all vertebrates including fish is hormonally regulated through highly conserved endocrine pathways, such as the brain-pituitary-gonad and brain-pituitary-renal axis. The liver is also an important organ involved in hormonal control of reproduction in fish and other egg-laying species. It does not synthesize any hormone but produces many important chemicals/molecules e.g. vitellogenin under the influence of hormone which is important for the success of reproduction (Fig. 3).
Effect of BPA on growth and development
The direct effect of BPA is on reproduction, but this chemical has also been found to negatively impact the development of the fish embryo and growth both at the larval and juvenile stage.
Exposure of 200 μg/L of BPA to Oryzias melastigma embryos for the whole embryonic stage, which started at 2 days postfertilization (dpf), resulted in reduced body length and width in larvae (Huang et al., 2012). Exposure of F0 generation of zebrafish to 10, 200 and 400 μg/L of BPA shows its effects in F2
Neurobehavioral effects and learning
Exposure of human-relevant concentrations of BPA during ontogenetic development resulted in learning deficits and behavioral abnormalities in rodents (Jones et al., 2011; Palanza et al., 2008). In zebrafish, exposure of low-dose BPA during the development of central nervous system (CNS) resulted in hyperactivity in larvae and learning delays in adults (Saili et al., 2012). Parental exposure of BPA resulted in altered sexually dimorphic behaviors in offspring (Jones et al., 2011; Negishi et al.,
Effect of BPA and analogs on metabolism
Bisphenol analogs induce metabolic disruption, hyper-insulinemia, and obesity in mammals (Alonso-Magdalena et al., 2015, 2006). However, little is known about the role of these compounds in disruption of metabolic health of aquatic animal models, particularly fish. Exposure of BPS to zebrafish led to insulin resistance and altered glucose homeostasis (Zhao et al., 2018). BPA exposure resulted in increased weight, hepatic triglyceride level, and lipid accumulation in male zebrafish (Sun et al.,
Effect of BPA and analogs on the immune system
Chemicals released into the waterbodies influence the immune competence of aquatic organisms. The endocrine and immune systems are intricately linked in vertebrates. Macrophages in fish have estrogen receptors. Effects of BPA and related bisphenols on immune regulation of macrophages may be due to interaction with nuclear factor -κB signaling and estrogen receptor α (Yang et al., 2015). Cytokines and chemokines are the pro-inflammatory mediators and effector molecules of the innate immune
Effect on the Thyroid Axis
Thyroid hormones are important for the maintenance of the physiology and metabolism of vertebrates including energy balance, growth and metabolism (Zhang et al., 2018). Thyroid hormones influence a wide variety of tissues and biological functions than any other hormones (Janz, 2000). In fish, thyroid hormones provide assistance to control osmoregulation, somatic growth, post-hatch metamorphosis and development. Thyroid hormones also regulate uptake of vitellogenin by the oocytes (Shibata et
Bisphenols and Cellular stress
Reactive oxygen species (ROS) are produced by normal metabolic products and they are normalized by enzymatic and non-enzymatic antioxidants. Oxidative stress arises when the balance between production and depletion of ROS is disturbed. ROS cause lipid peroxidation and damage cellular biomolecules (Valavanidis et al., 2006). Lipid peroxidation is the direct measure of tissue membrane damage due to reactive oxygen species (Blokhina et al., 2003). Enzymes in the body prevent oxidative stress.
Conclusions
Bisphenols are ubiquitous chemicals and have been detected in aquatic environments across the globe. All the literature discussed here suggests that BPA and analogs have a similar mode of action. The mechanisms of action are estrogen-, androgen-, and thyroid-mediated. These bisphenols also exert their effects through epigenetic and rapid signaling pathways. Fish physiological systems are severely affected by bisphenols. Reproduction is adversely affected in fish after exposure to BPA and its
Conflict of Interest
The authors declare no conflict of interest.
Funding
Funding was not received from public and private sector.
Author Contributions
Both authors contributed equally.
Declaration of Competing Interest
The authors report no declarations of interest.
References (220)
- et al.
Acute and long-term genotoxicity of deltamethrin to insulin-like growth factors and growth hormone in rainbow trout
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology
(2010) - et al.
Bisphenol-A acts as a potent estrogen via non-classical estrogen triggered pathways
Molecular and Cellular Endocrinology
(2012) - et al.
Occurrence of bisphenol A in surface water and uptake in fish: evaluation of field measurements
Chemosphere
(2002) - et al.
Xenoestrogens: The emerging story of Bisphenol A
Trends in Endocrinology and Metabolism
(1998) - et al.
Effects of the environmental estrogenic contaminants bisphenol A and 17α-ethinyl estradiol on sexual development and adult behaviors in aquatic wildlife species
General and Comparative Endocrinology
(2015) - et al.
Bisphenol A induces reactive oxygen species generation in the liver of male rats
Toxicology
(2003) - et al.
Bisphenol A accumulation in eggs disrupts the endocrine regulation of growth in rainbow trout larvae
Aquatic Toxicology
(2015) - et al.
Environmental estrogens can affect the function of mussel hemocytes through rapid modulation of kinase pathways
General and Comparative Endocrinology
(2004) - et al.
‘In vivo’ effects of Bisphenol A in Mytilus hemocytes: modulation of kinase-mediated signalling pathways
Aquatic Toxicology
(2005) - et al.
Reproductive toxicity of low level bisphenol A exposures in a two-generation zebrafish assay: Evidence of male-specific effects
Aquatic Toxicology
(2015)
Interference of endocrine disrupting chemicals with aromatase CYP19 expression or activity, and consequences for reproduction of teleost fish
General and Comparative Endocrinology
Reactive oxygen species, cellular redox systems, and apoptosis
Free Radical Biology and Medicine
Enzymes of triacylglycerol synthesis and their regulation
Progress in lipid research
An ecological assessment of bisphenol-A: Evidence from comparative biology
Reproductive Toxicology
Seasonal patterns in plasma levels of thyroid hormones and sex steroids in relation to photoperiod-induced changes in spawning time in rainbow trout, Salmo gairdneri
General and Comparative Endocrinology
Local expression of CYP19A1 and CYP19A2 in developing and adult killifish (Fundulus heteroclitus)
General and comparative endocrinology
Individual and joint toxic effects of pentachlorophenol and bisphenol A on the development of zebrafish (Danio rerio) embryo
Ecotoxicology and Environmental Safety
A new chapter in the bisphenol a story: Bisphenol S and bisphenol F are not safe alternatives to this compound
Fertility and Sterility
Evidence for two distinct KiSS genes in non-placental vertebrates that encode kisspeptins with different gonadotropin-releasing activities in fish and mammals
Molecular and Cellular Endocrinology
Detection of thyroid hormone receptor disruptors by a novel stable in vitro reporter gene assay
Toxicology in Vitro
Occurrence of phthalates and bisphenol A and F in the environment
Water Research
Occurrence of phthalates and bisphenol A and F in the environment
Water Research
Bisphenol A interacts with the estrogen receptor alpha in a distinct manner from estradiol
Molecular and cellular endocrinology
Neurobehavioral effects of bisphenol S exposure in early life stages of zebrafish larvae (Danio rerio)
Chemosphere
Oxidative stress, ion concentration change and immune response in gills of common carp (Cyprinus carpio) under long-term exposure to bisphenol A
Comparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
Effects of bisphenol A on lipid metabolism in rare minnow Gobiocypris rarus
Comparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
Environmental estrogens inhibit growth of rainbow trout (Oncorhynchus mykiss) by modulating the growth hormone-insulin-like growth factor system
General and Comparative Endocrinology
Adverse effects of bisphenol A on reproductive physiology in male goldfish at environmentally relevant concentrations
Ecotoxicology and Environmental Safety
Waterborne exposure to bisphenol F causes thyroid endocrine disruption in zebrafish larvae
Chemosphere
Monitoring of selected estrogenic hormones and industrial chemicals in groundwaters and surface waters in Austria
Science of The Total Environment
Teratogenic and anti-metamorphic effects of bisphenol A on embryonic and larval Xenopus laevis
General and comparative endocrinology
Effects of bisphenol A on thyroid hormone-dependent up-regulation of thyroid hormone receptor α and β and down-regulation of retinoid X receptor γ in Xenopus tail culture
Life Sciences
Occurrence and partitioning of bisphenol analogues in water and sediment from Liaohe River Basin and Taihu Lake
China. Water Research
Pre- and postnatal bisphenol A treatment results in persistent deficits in the sexual behavior of male rats, but not female rats, in adulthood
Hormones and Behavior
Bisphenol A acts differently from and independently of thyroid hormone in suppressing thyrotropin release from the bullfrog pituitary
General and Comparative Endocrinology
Long-term effects of a binary mixture of perfluorooctane sulfonate (PFOS) and bisphenol A (BPA) in zebrafish (Danio rerio)
Aquatic Toxicology
Neurochemical and behavioral analysis by acute exposure to bisphenol A in zebrafish larvae model
Chemosphere
Vitellogenesis as a biomarker of reproductive disruption by xenobiotics
Aquaculture
Molecular Mechanisms of Action of BPA
Dose-response : a publication of International Hormesis Society
Mechanism linking diabetes mellitus and obesity
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance
Environmental health perspectives
Prenatal Exposure to BPA and Offspring Outcomes: The Diabesogenic Behavior of BPA
Dose-response : a publication of International Hormesis Society
Bisphenol a in oocytes leads to growth suppression and altered stress performance in juvenile rainbow trout
PLoS ONE
Bisphenol a in oocytes leads to growth suppression and altered stress performance in juvenile rainbow trout
PLoS ONE.
Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): Evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation
Reprod Toxicol
Cross-species conservation of endocrine pathways: A critical analysis of tier 1 fish and rat screening assays with 12 model chemicals
Environmental Toxicology and Chemistry
Xenobiotic modulation of fish endocrine systems: Molecular and biochemical studies of the estrogen- and Ah-receptor pathways in Atlantic salmon (Salmo salar)
Occurrence of nonylphenol and bisphenol-A in surface waters from Portugal
Journal of the Brazilian Chemical Society
The hypothalamic-pituitary-thyroid (HPT) axis in fish and its role in fish development and reproduction
Critical Reviews in Toxicology
The Mechanisms of Action of PPARs
Annual Review of Medicine
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