TY - JOUR
T1 - In utero and lactational PCB exposure drives anatomic changes in the juvenile mouse bladder
AU - Keil Stietz, Kimberly P.
AU - Kennedy, Conner L.
AU - Sethi, Sunjay
AU - Valenzuela, Anthony
AU - Nunez, Alexandra
AU - Wang, Kathy
AU - Wang, Zunyi
AU - Wang, Peiqing
AU - Spiegelhoff, Audrey
AU - Puschner, Birgit
AU - Bjorling, Dale E.
AU - Lein, Pamela J.
N1 - Funding Information:
This work was supported by the United States National Institutes of Health grants [R00 ES029537 to KPKS, R01 ES014901, P01 ES011269, and P30 ES023513 to PJL, T32 ES007059 to SS, and T32 ES007015 to CLK]; and the United States Environmental Protection Agency grant [R833292 to PJL]. This project used core facilities supported by the MIND Institute Intellectual and Developmental Disabilities Research Center grant [U54 HD079125], the National Institutes of Health National Center for Advancing Translational Sciences grant [UL1 TR000002], the University of Wisconsin O'Brien Center for Benign Urologic Research grant [U54 DK104310 to DEB] and the Superfund Research Center at The University of Iowa grant [P42 ES013661]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the USEPA. Further, the NIH and USEPA did not endorse the purchase of any commercial products or services mentioned in the publication.
Funding Information:
This work was supported by the United States National Institutes of Health grants [ R00 ES029537 to KPKS, R01 ES014901 , P01 ES011269 , and P30 ES023513 to PJL, T32 ES007059 to SS, and T32 ES007015 to CLK]; and the United States Environmental Protection Agency grant [ R833292 to PJL]. This project used core facilities supported by the MIND Institute Intellectual and Developmental Disabilities Research Center grant [ U54 HD079125 ], the National Institutes of Health National Center for Advancing Translational Sciences grant [ UL1 TR000002 ], the University of Wisconsin O’Brien Center for Benign Urologic Research grant [ U54 DK104310 to DEB] and the Superfund Research Center at The University of Iowa grant [ P42 ES013661 ]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the USEPA. Further, the NIH and USEPA did not endorse the purchase of any commercial products or services mentioned in the publication.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/1
Y1 - 2021/1
N2 - Bladder dysfunction, including incontinence, difficulty emptying the bladder, or urgency to urinate is a pervasive health and quality of life concern. However, risk factors for developing these symptoms are not completely understood, and the influence of exposure to environmental chemicals, especially during development, on the formation and function of the bladder is understudied. Environmental contaminants such as polychlorinated biphenyls (PCBs) are known to pose a risk to the developing brain; however, their influence on the development of peripheral target organs, such as bladder, are unknown. To address this data gap, C57Bl/6J mouse dams were exposed to an environmentally-relevant PCB mixture at 0, 0.1, 1 or 6 mg/kg daily beginning two weeks prior to mating and continuing through gestation and lactation. Bladders were collected from offspring at postnatal days (P) 28–31. PCB concentrations were detected in bladders in a dose-dependent manner. PCB effects on the bladder were sex- and dose-dependent. Overall, PCB effects were observed in male, but not female, bladders. PCBs increased bladder volume and suburothelial βIII-tubulin-positive nerve density compared to vehicle control. A subset of these nerves were sensory peptidergic axons indicated by increased calcitonin gene-related protein (CGRP) positive nerve fibers in mice exposed to the highest PCB dose compared to the lowest PCB dose. PCB-induced increased nerve density was also positively correlated with the number of mast cells in the bladder, suggesting inflammation may be involved. There were no detectable changes in epithelial composition or apoptosis as indicated by expression of cleaved caspase 3, suggesting PCBs do not cause overt toxicity. Bladder volume changes were not accompanied by changes in bladder mass or epithelial thickness, indicating that obstruction was not likely involved. Together, these results are the first to suggest that following developmental exposure, PCBs can distribute to the bladder and alter neuroanatomic development and bladder volume in male mice.
AB - Bladder dysfunction, including incontinence, difficulty emptying the bladder, or urgency to urinate is a pervasive health and quality of life concern. However, risk factors for developing these symptoms are not completely understood, and the influence of exposure to environmental chemicals, especially during development, on the formation and function of the bladder is understudied. Environmental contaminants such as polychlorinated biphenyls (PCBs) are known to pose a risk to the developing brain; however, their influence on the development of peripheral target organs, such as bladder, are unknown. To address this data gap, C57Bl/6J mouse dams were exposed to an environmentally-relevant PCB mixture at 0, 0.1, 1 or 6 mg/kg daily beginning two weeks prior to mating and continuing through gestation and lactation. Bladders were collected from offspring at postnatal days (P) 28–31. PCB concentrations were detected in bladders in a dose-dependent manner. PCB effects on the bladder were sex- and dose-dependent. Overall, PCB effects were observed in male, but not female, bladders. PCBs increased bladder volume and suburothelial βIII-tubulin-positive nerve density compared to vehicle control. A subset of these nerves were sensory peptidergic axons indicated by increased calcitonin gene-related protein (CGRP) positive nerve fibers in mice exposed to the highest PCB dose compared to the lowest PCB dose. PCB-induced increased nerve density was also positively correlated with the number of mast cells in the bladder, suggesting inflammation may be involved. There were no detectable changes in epithelial composition or apoptosis as indicated by expression of cleaved caspase 3, suggesting PCBs do not cause overt toxicity. Bladder volume changes were not accompanied by changes in bladder mass or epithelial thickness, indicating that obstruction was not likely involved. Together, these results are the first to suggest that following developmental exposure, PCBs can distribute to the bladder and alter neuroanatomic development and bladder volume in male mice.
KW - Developmental origins of health and disease
KW - Lower urinary tract
KW - Peripheral nervous system
KW - Persistent organic pollutants
KW - Polychlorinated biphenyls
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U2 - 10.1016/j.crtox.2021.01.002
DO - 10.1016/j.crtox.2021.01.002
M3 - Article
AN - SCOPUS:85114900200
VL - 2
SP - 1
EP - 18
JO - Current Research in Toxicology
JF - Current Research in Toxicology
SN - 2666-027X
ER -