An In Silico and In Vitro Study for Investigating Estrogenic Endocrine Effects of Emerging Persistent Pollutants Using Primary Hepatocytes from Grey Mullet (<i>Mugil cephalus</i>)

Abstract

There is growing concern about the environmentally relevant concentrations of new emerging persistent organic pollutants, such as perfluorinated compounds and pharmaceuticals, which are found to bioaccumulate in aquatic organisms at concentrations suspected to cause reproductive toxicity due to the activation of estrogen receptor (ER) α and β subtypes. Here, we use a combined in silico and in vitro approach to evaluate the impact of perfluorononanoic acid (PFNA) and Enalapril (ENA) on grey mullet (Mugil cephalus) hepatic estrogen signaling pathway. ENA had weak agonist activity on ERα while PFNA showed moderate to high agonist binding to both ERs. According to these effects, hepatocytes incubation for 48 h to PFNA resulted in a concentration-dependent upregulation of ER and vitellogenin gene expression profiles, whereas only a small increase was observed in ERα mRNA levels for the highest ENA concentration. These data suggest a structure–activity relationship between hepatic ERs and these emerging pollutants.

Keywords

• endocrine disruptors
• <i>Mugil cephalus</i>
• PFNA