Linking in vitro estrogenicity to adverse effects in the inland silverside (Menidia beryllina)

Abstract

High-throughput cell assays that detect and integrate the response of multiple chemicals acting via a common mode of action have the potential to enhance current environmental monitoring practices. Establishing the linkage between in vitro and in vivo responses is key to demonstrating that in vitro cell assays can be predictive of ecologically relevant outcomes. The present study investigated the potency of 17β-estradiol (E2), estrone (E1), nonylphenol (NP), and treated wastewater effluent using the readily available GeneBLAzer estrogen receptor transactivation assay and 2 life stages of the inland silverside (Menidia beryllina). In vitro estrogenic potencies were ranked as follows: E2 > E1 >> NP. All 3 model estrogens induced vitellogenin and choriogenin expression in a dose-dependent manner in larvae and juveniles. However, apical effects were only found for E2 and E1 exposures of juveniles, which resulted in female-skewed sex ratios. Wastewater effluent samples exhibiting low in vitro estrogenicity (below the 10% effective concentration [EC10]), did not cause significant changes in M. beryllina. Significant induction of estrogen-responsive genes was observed at concentrations 6 to 26 times higher than in vitro responses. Gonadal feminization occurred at concentrations at least 19 to 26 times higher than the in vitro responses. These findings indicated that in vitro cell assays were more sensitive than the fish assays, making it possible to develop in vitro effect thresholds protective of aquatic organisms. Environ Toxicol Chem 2018;37:884-892. © 2017 SETAC.

Application of an Effects‐Based Monitoring Strategy to Assess the Impact of Contaminants on Fish Health in an Urbanized Watershed

“…The CECs may affect specific biological pathways, leading to sublethal effects such as metabolic, immune, and behavioral impairments. A number of studies have demonstrated that CECs can induce molecular changes at concentrations much lower than those eliciting morphological changes (Van den Belt et al 2004; Mehinto et al 2018). Therefore, evaluating standard toxicity endpoints such as growth, survival, and organosomatic indices could underestimate their impact on aquatic health.…”

“…This is consistent with other studies that reported estrogenic effects at concentrations found in the positive control (Shappell et al 2010). Previous research has documented the linkage among occurrence of estrogens, in vitro ERα bioactivity, and in vivo fish responses (Van den Belt et al 2004; Dobbins et al 2008; Mehinto et al 2018). These studies showed that in vitro bioassays and gene biomarkers are typically more sensitive than organismal responses, highlighting the value of a tiered effects–based monitoring strategy as an early warning tool.…”

“…River water samples with much lower concentrations of E1 (5-9 ng/L) and other estrogenic chemicals (e.g., 4-nonylphenol) did not exhibit any ERα bioactivity. Estrone is a weak estrogen with an estimated potency of approximately 0.03 to 0.08 relative to E2, depending on the cell bioassay platform used (Jarosova et al 2014;Mehinto et al 2015Mehinto et al , 2018. Thus, targeted chemistry data can explain the observed bioassay response (BEQ of~3 ng/L) in the E1 treatment.…”

“…Studies have demonstrated that in vitro bioassays can effectively screen for chemical occurrence and can assess water quality (Escher et al 2014; Mehinto et al 2015). In vitro bioassays have also been considered as alternatives to animal toxicity testing to inform on key molecular events (e.g., nuclear receptor activation) associated with key biological pathways and to prevent severe and irreversible effects in aquatic organisms (Piersma et al 2013; Mehinto et al 2018). In parallel, advances in omics technologies have resulted in the development of molecular assays that measure subtle changes in gene, protein, and metabolite biomarkers in organisms exposed to environmental stressors (Hook et al 2014).…”

Review of and Recommendations for Monitoring Contaminants and their Effects in the San Francisco Bay−Delta

“…They have recently served as a useful euryhaline model for the study of endocrine disruption and other categories of sub-lethal effects in the Bay−Delta and beyond(Brander et al 2013;Brander et al 2016a;DeCourten and Brander 2017;Mehinto et al 2018). M. beryllina are part of the EPA's Whole Effluent Toxicity (WET) Testing Program (NPDES WET;…”