>4000 pharmaceutical compounds (PCs) up to hundreds of tons are commercially produced, many of which are designed to improve animal and human health (Rehman et al., 2015). The pharmaceutical industry produces various types of formulations using various raw materials. In this way, the wastewater of these industries contains various types of organic and inorganic raw materials, intermediate compounds and final products. For example, (Altaf and Tasneem, 2010) reported that wastewater from pharmaceutical industries in Pakistan contains various compounds including antituberculosis products, antibiotics, antacids, multivitamins such as B1, B2, B6, B12, antitussives, rifampicin, isoniazid, pyrazinamide, ethambutol, Aluminum oxide, magnesium oxide, and sugar syrups (liquid glucose, malt extract). Therefore, the release of untreated industrial wastewater into natural water bodies or municipal wastewater leads to an increase in the complexity of these compounds and, as a result, an increase in their risk to the health of the entire ecosystem (Aziz et al., 2012). Most of these pharmaceutical production units are not follow the local environmental regulations and discharge their highly polluted industrial wastewater into aquatic ecosystems (rivers/seas) or municipal sewer networks without any treatment (Tong et al., 2011). For this reason, in recent years, the discharge of drugs in aquatic ecosystems, their fate and possible toxic effects have become one of the most important emerging research areas in the field of environment.

Glucocorticoids (GCs) are widely consumed in human and veterinary medicine mainly due to their anti-inflammatory and immunosuppressive properties. These compounds affect the hypothalamic-pituitary-adrenal axis (HPA) by effecting on the production and secretion of hypothalamic and pituitary hormones (Guiloski et al., 2017). According to (Kostich and Lazorchak, 2008), approximately 27,000 human prescriptions of glucocorticoids were prescribed in the United States alone in 2004.

Dexamethasone (DEXA) is the most potent glucocorticoid cortisone derivative widely used as a therapeutic to treat variant diseases in humans, including meningitis, myeloma and bronchiolitis. Moreover, since 2019 and with the spread of the corona virus worldwide, drugs such as remdesivir, lopinavir, emetine, chloroquine, and dexamethasone have been widely used to treat patients (Musee et al., 2021). In corona disease, pro-inflammatory cytokines cause diffuse lung damage. On the other hand, DEXA prolongs the analgesic effect and minimizes the destructive effect of cytokines, leading to delaying respiratory failure and eventual death in COVID-19 patients (Horby et al., 2021). This feature has led to a significant increase in the demand and use of this drug, especially in the last few years.

This compound is detected at relatively high levels in hospitals, households, and manufacturing plants wastewater (Herrero et al., 2013). The main route of DEX entering water resources is the discharge of wastewater from pharmaceutical companies and hospital treatment plants (Herrero et al., 2013). The estimated concentration of DEX in a sewage treatment plant was 1.7 ng/l in Japan (Nakayama et al., 2016) and 15 ng/l in Pierre Benite (Piram et al., 2008). Finally, the increasing release of DEXA into aquatic ecosystems, especially in recent years, has raised global concern regarding its possible harmful effects on aquatic organisms. Although there is limited research on the potential adverse effects of DEXA as an aquatic pollutant on aquatic animals, these studies have shown that DEXA can be considered an endocrine disruptor. (Milla et al., 2009) reported decreased level of 11-ketotestosterone production, smaller gonads and poor sperm quality in male fish exposed to increased level of DEXA.

Aromatase cytochrome P450arom (cyp19), encoded by the CYP19 gene, is responsible for the conversion of androgens (testosterone and androstenedione) to estrogens (Dong et al., 2008). Most mammals have only one form of this gene (Boon et al., 2010), while in many fish two structurally and functionally different CYP19 genes are expressed: CYP19a (CYP19a1/aromatase A/AroA) and CYP19b (CYP19a2/ aromatase B/AroB) (Simpson et al., 2002). The CYP19a gene expressed predominantly in the ovary and to a very small amount in the testicles, while the CYP19b gene expressed primarily in the brain of both sexes) (Simpson et al., 2002). Research has shown that inhibition of aromatase in undifferentiated female fish resulted in complete masculinization of an all-female population (Guiguen et al., 1999). For this reason, investigating the adverse effects of environmental pollutants on this enzyme is an important issue in environmental research (Dong et al., 2008).

In this regard, considering the novelty of research on pharmaceutical pollutants, especially in the Persian Gulf, and also regarding the important role of aromatase in fish reproduction and development, the present study aimed to investigate the adverse effects of DEX on brain, ovarian and testicular aromatase activities in the Persian Gulf Arabian sea bream, Acanthopagrus arabicus, in vitro. A. arabicus was selected due to its commercial importance. This fish is one of the most popular fish in the countries along the Persian Gulf, and due to its economic importance, it is also being cultivated in the south of Iran. In this regard, ovarian, testis and brain cell culture systems, obtained from A. arabicus, were used to investigate the changes in aromatase activity and steroid production by cells treated with DEX.