Review
Detrimental Effects of Bisphenol Compounds on Physiology and Reproduction in Fish: A Literature Review

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Abstract

Bisphenol-A is one of the most studied endocrine-chemicals, which is widely used all over the world in plastic manufacture. Because of its extensive use, it has become one of the most abundant chemical environmental pollutants, especially in aquatic environments. BPA is known to affect fish reproduction via estrogen receptors but many studies advocate that BPA affects almost all aspects of fish physiology. The possible modes of action include genomic, as well as and non-genomic mechanisms, estrogen, androgen, and thyroid receptor-mediated effects. Due to the high detrimental effects of BPA, various analogs of BPA are being used as alternatives. Recent evidence suggests that the analogs of BPA have similar modes of action, with accompanying effects on fish physiology and reproduction. In this review, a detailed comparison of effects produced by BPA and analogs and their mode of action is discussed.

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)

  • K. Cheshenko et al.

    Interference of endocrine disrupting chemicals with aromatase CYP19 expression or activity, and consequences for reproduction of teleost fish

    General and Comparative Endocrinology

    (2008)
  • M.L. Circu et al.

    Reactive oxygen species, cellular redox systems, and apoptosis

    Free Radical Biology and Medicine

    (2010)
  • R.A. Coleman et al.

    Enzymes of triacylglycerol synthesis and their regulation

    Progress in lipid research

    (2004)
  • D.A. Crain et al.

    An ecological assessment of bisphenol-A: Evidence from comparative biology

    Reproductive Toxicology

    (2007)
  • D.G. Cyr et al.

    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

    (1988)
  • W. Dong et al.

    Local expression of CYP19A1 and CYP19A2 in developing and adult killifish (Fundulus heteroclitus)

    General and comparative endocrinology

    (2008)
  • Z. Duan et al.

    Individual and joint toxic effects of pentachlorophenol and bisphenol A on the development of zebrafish (Danio rerio) embryo

    Ecotoxicology and Environmental Safety

    (2008)
  • S. Eladak et al.

    A new chapter in the bisphenol a story: Bisphenol S and bisphenol F are not safe alternatives to this compound

    Fertility and Sterility

    (2015)
  • A. Felip et al.

    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

    (2009)
  • J. Freitas et al.

    Detection of thyroid hormone receptor disruptors by a novel stable in vitro reporter gene assay

    Toxicology in Vitro

    (2011)
  • H. Fromme et al.

    Occurrence of phthalates and bisphenol A and F in the environment

    Water Research

    (2002)
  • H. Fromme et al.

    Occurrence of phthalates and bisphenol A and F in the environment

    Water Research

    (2002)
  • J.C. Gould et al.

    Bisphenol A interacts with the estrogen receptor alpha in a distinct manner from estradiol

    Molecular and cellular endocrinology

    (1998)
  • J. Gu et al.

    Neurobehavioral effects of bisphenol S exposure in early life stages of zebrafish larvae (Danio rerio)

    Chemosphere

    (2019)
  • Z. Gu et al.

    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

    (2020)
  • Y. Guan et al.

    Effects of bisphenol A on lipid metabolism in rare minnow Gobiocypris rarus

    Comparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology

    (2016)
  • A.M. Hanson et al.

    Environmental estrogens inhibit growth of rainbow trout (Oncorhynchus mykiss) by modulating the growth hormone-insulin-like growth factor system

    General and Comparative Endocrinology

    (2014)
  • A. Hatef et al.

    Adverse effects of bisphenol A on reproductive physiology in male goldfish at environmentally relevant concentrations

    Ecotoxicology and Environmental Safety

    (2012)
  • G.-M. Huang et al.

    Waterborne exposure to bisphenol F causes thyroid endocrine disruption in zebrafish larvae

    Chemosphere

    (2016)
  • P. Hohenblum et al.

    Monitoring of selected estrogenic hormones and industrial chemicals in groundwaters and surface waters in Austria

    Science of The Total Environment

    (2004)
  • S. Iwamuro et al.

    Teratogenic and anti-metamorphic effects of bisphenol A on embryonic and larval Xenopus laevis

    General and comparative endocrinology

    (2003)
  • S. Iwamuro et al.

    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

    (2006)
  • H. Jin et al.

    Occurrence and partitioning of bisphenol analogues in water and sediment from Liaohe River Basin and Taihu Lake

    China. Water Research

    (2016)
  • B.A. Jones et al.

    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

    (2011)
  • M. Kaneko et al.

    Bisphenol A acts differently from and independently of thyroid hormone in suppressing thyrotropin release from the bullfrog pituitary

    General and Comparative Endocrinology

    (2008)
  • S. Keiter et al.

    Long-term effects of a binary mixture of perfluorooctane sulfonate (PFOS) and bisphenol A (BPA) in zebrafish (Danio rerio)

    Aquatic Toxicology

    (2012)
  • S.S. Kim et al.

    Neurochemical and behavioral analysis by acute exposure to bisphenol A in zebrafish larvae model

    Chemosphere

    (2020)
  • D. Kime et al.

    Vitellogenesis as a biomarker of reproductive disruption by xenobiotics

    Aquaculture

    (1999)
  • F. Acconcia et al.

    Molecular Mechanisms of Action of BPA

    Dose-response : a publication of International Hormesis Society

    (2015)
  • A. Algoblan et al.

    Mechanism linking diabetes mellitus and obesity

    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy

    (2014)
  • P. Alonso-Magdalena et al.

    The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance

    Environmental health perspectives

    (2006)
  • P. Alonso-Magdalena et al.

    Prenatal Exposure to BPA and Offspring Outcomes: The Diabesogenic Behavior of BPA

    Dose-response : a publication of International Hormesis Society

    (2015)
  • N. Aluru et al.

    Bisphenol a in oocytes leads to growth suppression and altered stress performance in juvenile rainbow trout

    PLoS ONE

    (2010)
  • N. Aluru et al.

    Bisphenol a in oocytes leads to growth suppression and altered stress performance in juvenile rainbow trout

    PLoS ONE.

    (2010)
  • B.M. Angle et al.

    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

    (2013)
  • G.T. Ankley et al.

    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

    (2013)
  • A. Arukwe

    Xenobiotic modulation of fish endocrine systems: Molecular and biochemical studies of the estrogen- and Ah-receptor pathways in Atlantic salmon (Salmo salar)

    (1998)
  • D. Azevedo et al.

    Occurrence of nonylphenol and bisphenol-A in surface waters from Portugal

    Journal of the Brazilian Chemical Society

    (2001)
  • M.L. Balton et al.

    The hypothalamic-pituitary-thyroid (HPT) axis in fish and its role in fish development and reproduction

    Critical Reviews in Toxicology

    (2007)
  • J. Berger et al.

    The Mechanisms of Action of PPARs

    Annual Review of Medicine

    (2002)
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