Use of Japanese medaka fish as a model organism to study the endocrine disrupting effects of toxic compounds.
Creators: name: Dasmahapatra, Asok
name: Myla, Anitha
name: Tchounwou, Paul
Publisher: name: figshare
Year: 2023
Subjects: Environmental assessment and monitoring

description: At the onset of 21st century, due to the rapid growth of high throughput technologies in medicine, engineering, agriculture, and material sciences, many new chemical compounds were produced and their continued manufacturing, transport, use, and disposal, lead to a high probability of environmental contamination. Many of these compounds are potential endocrine disruptors (EDs), which interfere with the endocrine system in humans and other animals. Initial studies indicated that endocrine disrupting chemicals (EDCs) affect sexual development and reproduction and can lead to cancer, obesity, cardiovascular, and neurobehavioral disorders. Research in animal models, clinical observations in humans, or epidemiological studies have indicated that the potential mechanisms underlying the adverse effects of EDCs are associated with the dysregulation of nuclear receptors, including estrogen, androgen, progesterone, thyroid, and retinoid receptors. In the environment, aquatic ecosystems have traditionally been the depository of many anthropogenic substances, including various organic/inorganic contaminants, pesticides, pharmaceuticals, and personal care products (PCP), which are frequently detected at nanogram to microgram/ liter levels. PCPs include a large and diverse group of medicinal products used for the diagnosis, cure, mitigation, treatment, or prevention of diseases in humans and animals. The main sources of PCPs entering the environment are industrial manufacturing, hospitals, or domestic effluents; whereas the pharmaceuticals present in the aquatic environment as parent compounds or metabolites came from wastewater discharges or agricultural runoff containing pesticides and animal husbandry hormones and medicine. While the release of these compounds into the aquatic environment as waterborne EDCs can affect the life cycles of aquatic animals, such as fish and other vertebrate and invertebrate organisms. Many fish species are exposed to these chemicals either throughout their life cycle or at specific period of life stages such as embryos, larvae, or adults. Based on their importance, several small fish models, including zebrafish (<em>Danio rerio</em>), Japanese medaka (<em>Oryzias latipes</em>), and fathead minnow (<em>Pimephales promelas</em>) have been used in the implementation of testing and assessment for endocrine active chemicals, consisting of a two-tiered strategy. Due to their small size and high fecundity, the husbandry of these fish species in the laboratory is cost-effective and even cheaper than that of mammals. Although overall research on EDCs in teleost fish has initially focused on their effects on the reproductive structures and functions, in the present review, we have focused on the Japanese medaka (<em>Oryzias latipes</em>) as a model organism for evaluation of the endocrine organs disrupted by EDCs. Despite its small size, short life cycle, high daily fecundity, Japanese medaka has both genotypic and phenotypic sexual dimorphism and have been widely used for studies in genetics, embryology, cytology, and ecotoxicology. Moreover, several endpoints in medaka including alterations to sex ratios, development of testis-ova, enhancement of plasma vitellogenin level in male fish and alteration in hepatic vitellogenin (<em>vtg</em>) and choriogenin (<em>chg</em>) genes and many observed features in secondary sex characters (anal fin papillae in males) have been identified as indicators of endocrine disruption at the Tier 1 level. In addition, the medaka extended one-generation reproduction test (MEOGRT), a Tier-2 study in the US Environmental Protection Agency’s Endocrine Disruptor Screening Program (EDSP) and a level-5 study in the Organization for Economic Cooperation and Development’s (OECD) conceptual framework have significantly contributed during to the evaluation of EDCs released into the environment. To identify the EDCs disposed in the aquatic environment, we followed a strategy of searching peer-reviewed publications on Japanese medaka that focused on endocrine disrupting effects at the morphological, biochemical, and genetic levels. Our effort identified 195 publications consisting of 102 chemicals belonging to estrogenic, androgenic, thyroid, and steroidogenic pathways (EATS) with agnostic and antagonistic effects. This study will further strengthen the potential of this fish model as a screening tool for the EDCs found in the environment.