RESUMO
Lower urinary tract symptoms (LUTS) greatly reduce quality of life. While LUTS etiology is not completely understood, it is plausible that environmental contaminants could play a role. Polychlorinated biphenyls (PCBs), are a group of persistent environmental toxicants frequently documented in animal and human tissues. PCBs are capable of influencing voiding function in mouse offspring exposed developmentally, however whether PCB exposure during adulthood can also influence voiding dynamics is unknown. Therefore, the purpose of this study was to determine whether PCB exposure in adult female mice can impact voiding function. As part of a larger study to generate developmentally exposed offspring, adult female C57Bl/6J mice were dosed orally with the MARBLES PCB mixture (0.1, 1, or 6 mg/kg/day) or vehicle control beginning two weeks before mating and throughout gestation and lactation (9 weeks). Adult dosed female dams then underwent void spot assay, uroflowmetry, and anesthetized cystometry to assess voiding function. Bladder contractility was assessed in ex vivo bladder bath assays, and bladders were collected for morphology and histology assessments. While voiding behavior endpoints were minimally impacted, alterations to bladder contractility dynamics were more pronounced. Adult female mice dosed with 1 mg/kg/d PCB showed an increase in urine spots 2-3 cm2 in size, increased bladder contractility in response to electrical field stimulation, and decreased bladder wall thickness compared to vehicle control. PCBs also altered contractile response to cholinergic agonist in a dose-dependent manner. Overall, these results indicate that exposure to PCBs in adult female mice is sufficient to produce changes in bladder physiology. These results also highlight the critical role of timing of exposure in influencing voiding function.
RESUMO
Polychlorinated biphenyls (PCBs) are persistent organic pollutants linked to deleterious health outcomes, including voiding dysfunction in developmentally exposed mice. Changes in prostate volume and/or extracellular matrix composition are associated with voiding dysfunction in men and animal models. Whether PCB-induced changes in voiding function in male mice occur in part via alterations to the prostate or an alternate mechanism is unclear. Therefore, we tested whether developmental exposure to the MARBLES PCB mixture altered prostate morphology in young adult offspring. C57Bl/6J female mice were dosed daily with the MARBLES PCB mixture at 0, 0.1, 1 or 6 mg/kg/d for two weeks prior to mating and through gestation and lactation, offspring were collected at 6 weeks of age. Ventral prostate mass was decreased in the 1 mg/kg/d PCB group compared to other PCB groups. There were no PCB-induced changes in prostate smooth muscle thickness, apoptosis, proliferation, or testes mass. PCBs impacted the prostate extracellular matrix; anterior prostate collagen density was decreased in the 1 mg/kg/d PCB group compared to all other groups. Normalized bladder volume was increased in male and female offspring in the 6 mg/kg/d PCB group compared to control. No change in water consumption, bladder mass or bladder smooth muscle thickness accompanied changes in bladder volume. Urine and serum creatinine concentrations were elevated but only in male mice. Together, these results suggest that developmental exposure to PCBs can influence prostate wet weight and prostate/bladder morphology, but PCBs do not promote prostate enlargement. Whether these changes persist throughout adult life and how they contribute to voiding function in animal models and humans is of future interest.