Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice
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 previ...
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Elsevier
2025-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X25000131 |
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| author | Monica Ridlon Audrey Spiegelhoff Conner L Kennedy Thomas Lavery Kathy Wang Julia Tlapa Tamryn Jordan Lindsey Felth Tanaka Kimberly Keil Stietz |
| author_facet | Monica Ridlon Audrey Spiegelhoff Conner L Kennedy Thomas Lavery Kathy Wang Julia Tlapa Tamryn Jordan Lindsey Felth Tanaka Kimberly Keil Stietz |
| author_sort | Monica Ridlon |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-240ce955f40d4e30b99ff2aca933b46e |
| institution | Kabale University |
| issn | 2666-027X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Current Research in Toxicology |
| spelling | doaj-art-240ce955f40d4e30b99ff2aca933b46e2025-08-20T03:24:36ZengElsevierCurrent Research in Toxicology2666-027X2025-01-01810022710.1016/j.crtox.2025.100227Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in miceMonica Ridlon0Audrey Spiegelhoff1Conner L Kennedy2Thomas Lavery3Kathy Wang4Julia Tlapa5Tamryn Jordan6Lindsey Felth Tanaka7Kimberly Keil Stietz8Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USADepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USADepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USADepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USADepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USADepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USADepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USADepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USACorresponding author.; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USAPolychlorinated 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.http://www.sciencedirect.com/science/article/pii/S2666027X25000131MARBLES PCBDevelopmental and reproductive toxicologyLower urinary tractCystometryCapsaicinTRPV1 |
| spellingShingle | Monica Ridlon Audrey Spiegelhoff Conner L Kennedy Thomas Lavery Kathy Wang Julia Tlapa Tamryn Jordan Lindsey Felth Tanaka Kimberly Keil Stietz Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice Current Research in Toxicology MARBLES PCB Developmental and reproductive toxicology Lower urinary tract Cystometry Capsaicin TRPV1 |
| title | Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice |
| title_full | Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice |
| title_fullStr | Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice |
| title_full_unstemmed | Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice |
| title_short | Developmental polychlorinated biphenyl (PCB) exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice |
| title_sort | developmental polychlorinated biphenyl pcb exposure impacts on voiding physiology persist into adulthood and influence sensitivity to bladder stimuli in mice |
| topic | MARBLES PCB Developmental and reproductive toxicology Lower urinary tract Cystometry Capsaicin TRPV1 |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X25000131 |
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