Sustainability Committee - Zebrafish in ecotoxicology
Zebrafish in ecotoxicology - a sustainable model to study the impact of environmental toxins on human health
(Contributed by Manjari Trivedi on behalf of the Sustainability Committee, IZFS)
Introduction
Most of us have used canned tomato purée to prepare sauces and curries but are unaware that many canned foods can be contaminated with bisphenol A (BPA). The inner lining of metal cans is coated with plastic, and many of them are made of BPA-containing plastic material. Over time, BPA leaches into the food contents, causing millions of people to be exposed to it through their food, posing a risk to their health. Through our food and other sources, we also get exposed to many other environmental toxins such as heavy metals, pharmaceuticals, pesticides, microplastics, and industrial chemicals. Some of these toxins have been well-studied by environmental toxicologists to understand their effects on human health and our ecosystem, and zebrafish have been used in environmental toxicology since at least the early 1990s.
Zebrafish- a powerful model to study ecotoxicology
Zebrafish is a powerful model to study environmental toxins. They share a significant genetic similarity with humans, facilitating the translation of zebrafish research to humans. They are also cost-effective to maintain and breed, thus making them accessible for research. More importantly, zebrafish embryos are transparent and develop rapidly. So, any adverse effect of a toxin on the developing tissues of an embryo is easy to observe and allows for much quicker observations than other rodent in vivo models. Also, a single adult female zebrafish can lay hundreds of eggs, which permits high throughput chemical screening in a short amount of time. Moreover, zebrafish model is great for studying trans-generational effects of environmental toxins by allowing easier genetic manipulations and methods to study epigenetic modifications to DNA, which can then potentially be translated into human health research.
More about BPA
BPA is an estrogen mimic and has been classified as an endocrine-disrupting chemical (EDC). It is a pervasive contaminant which leaches from the packaging of canned foods, plastic beverage containers, household items like water bottles and food storage containers, and even dental and medical products. BPA then gets into the human body after consumption of food and beverages in packaging containing BPA, through commercial receipt paper used in cash register receipts, and through many other environmental sources. Further, BPA enters our water supply systems through pipes and industrial manufacturing processes of BPA-containing products and can also enter the environment through wastewater effluent and landfills.
Effect of BPA on human health and disease
The first-ever record of human illness caused by BPA was in 1957 [1]. Since then, many more studies have identified how BPA exposure affects our health. To learn more about the effects of BPA on human health, we talked with the EDC experts, Dr Patricia Hunt, a Regents professor at Washington State University and Dr Patrice Delaney, a postdoctoral research fellow at Harvard Medical School. They both agreed that the use of BPA-containing consumer products is concerning and has been associated with several health problems. Experimental studies in mouse, rhesus monkey, Caenorhabditis elegans, and embryonic stem cell cultures have all confirmed that BPA exposure interferes with embryonic development and can have long-lasting effects on tissue development, cause behavioral and cognitive defects, metabolic disorders, and increased susceptibility to cardiovascular diseases and cancer. Arguably, these ill effects of BPA were observed in animal models and, hence, may not apply to human beings, but Dr Hunt also tells us about a study that found a link between higher BPA levels in women undergoing IVF treatments and number of viable eggs obtained for the treatment. BPA has also been linked with diminished male fertility and reproductive function. Overall, it is safe to conclude that BPA has harmful health consequences, and we must protect ourselves from environmental toxins like BPA.
Steps to limit BPA exposure
When we asked Dr Delaney how to protect ourselves from BPA exposure, she suggested that we heat our food in non-plastic containers and stop using old plastic items, as heat can release BPA into food. Dr Hunt also suggested we switch to glass or metal water bottles and food containers whenever possible. In fact, it may be helpful to handwash plastics and avoid putting them in the dishwasher to prevent contamination of other items in the dishwasher and prevent the release of microplastic-contaminated water into the sewage system and from there on to our surroundings. Another important point raised by both Dr Hunt and Dr Delaney was that nowadays, “BPA-free” products are easily available on the market. However, these items contain BPA analogues, whose safety has not been properly established before making them available to the consumers, posing an enormous health risk to the population.
Zebrafish in ecotoxicological health studies
A huge reason why we have so many health risk-posing products easily available to us is due to the lack of regulatory standards to effectively study the harmful effects of BPA and other environmental toxins on people. Often, the need to quickly commercialize a product supersedes the requirement to do intensive safety testing. Using the zebrafish model can help us do both: product commercialization and proper product safety testing. There has been a recent uptick in the number of academic research studies implementing the zebrafish model to study BPA and they have found damaging effects of BPA on a wide range of tissues in the body. A 2024 study reports that BPA exposure in zebrafish caused hepatotoxicity by inducing excessive oxidative stress and cell death [2]. Another study found that BPA also interferes with chondrogenesis and therefore, affecting musculoskeletal and craniofacial development [3, 4]. BPA caused smaller body and organ size, defective development of various tissues, increased mortality, poor nutrition uptake, disrupted metabolism, cell apoptosis, endoplasmic reticulum (ER) stress, hyper-inflammation, and pathological changes in the tissues [1, 4, 5, 6, 7, 8]. Its exposure even resulted in altered function of the zebrafish gut microbiota- liver- brain axis [9]. More concerningly, a study in zebrafish also presented evidence of transgenerational effect of BPA where even a very small BPA exposure caused ovary and testes retraction in zebrafish, organ malformation, and poor survival rates in offsprings [10].
Very limited studies have been published on studying the toxic effects of BPA analogues such as fluorene-9-bisphenol (BHPF), which showed increased cell death upon exposure, resulting in cardiac and vascular defects in zebrafish embryos [6, 11]. Moreover, BPA and its analogues are toxic to the reproductive neuroendocrine system by acting through aromatase and estrogen receptors [12]. We need more academic and regulatory studies investigating the effects of BPA and its analogues that are present in consumer products. For this, zebrafish is a valuable model, and it can be applied to study the effect of various EDCs and other toxins on tissue development and health. Studies using the zebrafish model can also be extrapolated to other species, thus allowing us to study a wide range of subjects from human health to environmental biology.
Conclusion
In conclusion, zebrafish is a powerful and sustainable model for studying the impact of environmental toxins like BPA on human health. By leveraging zebrafish in ecotoxicology, we can improve product safety testing and regulatory processes, ultimately protecting us and the ecosystems in which we live from harmful environmental contaminants.
References
[1] L. E. Gaul, 1960, Sensitivity to Bisphenol A, Arch Dermatol.; 82(6):1003.
[2] Wang, Y., Wu, J., Wang, D., et al., 2024, BPA induces hepatotoxicity in zebrafish through oxidative stress and apoptosis pathway, Fish Physiol Biochem.; 50(2):403-412.
[3] Duan, L., Deng, H., Zhang, Q., et al., 2023, Environmentally relevant levels of BPA and NOR disturb early skeletal development in zebrafish, Comp Biochem Physiol C Toxicol Pharmacol.; 271.
[4] Zhu, Z., Wang, J., Cao, Q., et al., 2022, Long-term BPA exposure leads to bone malformation and abnormal expresison of MAPK/Wnt/FoxO signaling pathway genes in zebrafish offspring, Ecotoxicol Environ Saf.; 245: 114082.