Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice

Abstract

Polychlorinated biphenyls (PCBs) are toxicants present in the environment, foodstuff, animal and human tissues. PCBs are linked to numerous adverse health effects; however, impacts of developmental PCB exposure on lower urinary tract function are a comparatively newer area of interest. We have previously found developmental exposure (in utero and lactational) to a human-relevant PCB mixture in mice leads to sex- and dose- dependent changes to urinary voiding physiology at 6 weeks of age. This study expands upon previous findings to investigate if developmental PCB-induced urinary voiding phenotypes persist or shift as mice age to 12 weeks of age. Urinary voiding physiology testing through void spot assays, uroflowmetry, and cystometry demonstrated several sex- and dose- dependent effects of PCB exposure at 12 weeks of age. Further, patterns of dysfunction were either maintained, newly acquired, or reversed compared to those from younger adult mice in a previous study. Here, developmental PCB exposure decreased number of small urine spots in adult male and female mice in a dose dependent manner, and female mice had more frequent voiding events assessed by anesthetized cystometry. Mice also had PCB dose-dependent changes to urinary voiding physiology when challenged with intravesical capsaicin infusion to target transient receptor potential cation channel subfamily V member 1 (TRPV1)-mediated pathways. PCBs either blocked or exacerbated capsaicin induced responses depending on the endpoint examined, suggesting this pathway may play a role in PCB-dependent changes in voiding. PCBs also had subtle impacts on prostate wet weight, with high PCB doses reducing tissue mass compared to low PCB doses, while none differed from vehicle. This study demonstrates developmental exposure to PCBs continues to impact lower urinary tract function in adulthood to at least 12 weeks of age both during homeostatic conditions and upon challenge of capsaicin. Better understanding of how early life stressors like PCBs contribute to aging-associated voiding dysfunction are imperative as these findings may help mitigate risk or improve treatment strategies for patients suffering from lower urinary tract symptoms.