Abstract
Bladder inflammation is associated with several lower urinary tract symptoms that greatly reduce quality of life, yet contributing factors are not completely understood. Environmental chemicals are plausible mediators of inflammatory reactions within the bladder. Here, we examine whether developmental exposure to polychlorinated biphenyls (PCBs) leads to changes in immune cells within the bladder of young mice. Female mice were exposed to an environmentally relevant mixture of PCBs through gestation and lactation, and bladders were collected from offspring at postnatal day (P) 28–31. We identify several dose- and sex-dependent PCB effects in the bladder. The lowest concentration of PCB (0.1 mg/kg/d) increased CD45+ hematolymphoid immune cells in both sexes. While PCBs had no effect on CD79b+ B cells or CD3+ T cells, PCBs (0.1 mg/kg/d) did increase F4/80+ macrophages particularly in female bladder. Collagen density was also examined to determine whether inflammatory events coincide with changes in the stromal extracellular matrix. PCBs (0.1 mg/kg/d) decreased collagen density in female bladder compared to control. PCBs also increased the number of cells undergoing cell division predominantly in male bladder. These results implicate perturbations to the immune system in relation to PCB effects on the bladder. Future study to define the underlying mechanisms could help understand how environmental factors can be risk factors for lower urinary tract symptoms.
Highlights
Lower urinary tract symptoms (LUTS) greatly impact quality of life
Since polychlorinated biphenyls (PCBs) cause inflammation in many tissues [38,44,49,50], and bladder inflammation can be a driver of LUTS [3], we tested and confirmed that mice developmentally exposed to MARBLES PCB develop low-grade bladder inflammation as young adults
PCB exposure did not significantly change the bladder abundance of CD79b-positive B cells; we identified a surprising overall main effect of sex with increases in total CD79b-positive cells in female compared to male bladder tissue (Figure 2C)
Summary
Lower urinary tract symptoms (LUTS) greatly impact quality of life. Patients seeking medical attention for these symptoms represent a significant health care cost [1,2]. There are known factors which can give rise to bladder inflammation including infection (typically acute inflammation), genetics, autoimmunity and dietary influences [3,4]. Consequences of these factors can lead to states of chronic inflammation, which can induce fibrosis and continuation or worsening of symptoms such as pain, urgency and frequency [3,5,6]. Despite the use of chemicals to model bladder inflammation in rodents, whether exposure to ubiquitous environmental chemicals such as polychlorinated biphenyls (PCBs) can contribute to a state of chronic bladder inflammation, fibrosis and bladder dysfunction is understudied
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