Linking Chemical Tolerance to Reproductive Resilience: CYP1A as a Metric for Predicting Fish Species Distributions in Chemically-Impacted Habitats

Many of the pollutants present in our waterbodies today exert sublethal effects with farreaching impacts on future generations. Polychlorinated biphenyls (PCBs) are ubiquitous aquatic pollutants with significant sublethal effects in both humans and fish, including altered reproduction, hormone disruption, immunosuppression and carcinogenesis. Significant levels of environmental PCBs in Kentucky have led to the posting of fish advisories in several Kentucky waterways (Kentucky Division of Water). The focus of the present study is the Town Branch-Mud River (TB/MR) system in Southwestern Kentucky, a PCB-contaminated area currently undergoing remediation. This proposal addresses several needs identified by the Water Science and Technology Board [7], including the need to understand the impact of contaminants on higher organisms, to monitor the time course of recovery following contamination, and to evaluate the effectiveness of management efforts to improve water quality. The problem: PCBs are potent disruptors of reproductive function in fish. Although we and others have demonstrated that fish can develop resistance to some deleterious effects of PCBs, whether this resistance protects them from PCB-mediated reproductive toxicity is not known. Results of our previous USGS-funded research (OlHQGR0133) demonstrate that several resident fish species in the TB/MR system (Logan County, KY) have developed resistance to PCBs as evidenced by suppressed inducibility of the pollutant-inducible enzyme, CYP1A [9], likely in response to the extraordinarily high PCB concentrations present in this waterway, despite extensive remediation [13]. We propose to extend these studies to determine whether development of PCB-resistance has altered reproductive function in resident Town Branch fish. We hypothesize that there is a mechanistic link between resistance to PCB mediated induction of CYPIA and resistance to the deleterious effects of PCBs on reproductive function. Our objectives are to determine 1) if PCB-resistant resident populations in Town Branch have altered reproductive function compared to non-resistant populations of the same and different species, 2) whether species abundance reflects species-specific ability to develop resistance, and 3) whether altered regulation of the pollutant-metabolizing enzYme, CYPIA (a defining characteristic of PCB-resistance in fish) is mechanistically linked to reproductive function. Blocking CYPIA activity in fish blocks PCB effects on reproductive hormones [32], indicating a link between CYPIA, PCBs and reproductive function.