In utero and lactational PCB exposure drives anatomic changes in the juvenile mouse bladder
| Autor: | Kathy Wang, Peiqing Wang, Pamela J. Lein, Alexandra Nunez, Dale E. Bjorling, Birgit Puschner, Kimberly P. Keil Stietz, Zun-Yi Wang, Audrey Spiegelhoff, Conner L. Kennedy, Sunjay Sethi, Anthony Valenzuela |
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| Rok vydání: | 2022 |
| Předmět: |
Urologic Diseases
Offspring polychlorinated biphenyls Health Toxicology and Mutagenesis media_common.quotation_subject Physiology Calcitonin gene-related peptide Lower urinary tract Toxicology urologic and male genital diseases Applied Microbiology and Biotechnology Urination Article Polychlorinated biphenyls peripheral nervous system RA1190-1270 Lactation Medicine 2.1 Biological and endogenous factors Aetiology media_common ComputingMethodologies_COMPUTERGRAPHICS Pediatric business.industry Persistent organic pollutants Neurosciences Developmental origins of health and disease medicine.anatomical_structure In utero Peripheral nervous system Toxicology. Poisons Toxicity Gestation business |
| Zdroj: | Current Research in Toxicology Current Research in Toxicology, Vol 2, Iss, Pp 1-18 (2021) |
| ISSN: | 2666-027X |
| Popis: | Graphical abstract Highlights • PCB effects in bladder are observed in male but not female mice. • Developmental PCB exposure increases young adult mouse bladder volume. • Developmental PCB exposure increases nerve fiber density in bladder suburothelium. • Bladder mast cells are positively correlated with nerve density in PCB exposed mice. 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. |
| Databáze: | OpenAIRE |
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