The Bladder Is a Novel Target of Developmental Polychlorinated Biphenyl Exposure Linked to Increased Inflammatory Cells in the Bladder of Young Mice

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.

Polychlorinated Biphenyls (PCBs) Impact Prostatic Collagen Density and Bladder Volume in Young Adult Mice Exposed during in Utero and Lactational Development

“…Changes in collagen fibril distribution and remodeling in the prostate and bladder extracellular matrix have been shown to occur in an aged mouse model developmentally exposed to dioxin [ 8 ]. We have recently shown that developmental PCB exposure can decrease bladder collagen density in young mouse offspring [ 25 ]. Therefore, we wanted to determine whether developmental exposure to PCBs can alter collagen density within the prostate in young adult mouse offspring and whether these changes coincide with observed changes in prostate wet weight ( Figure 1 ) or previously reported voiding dysfunction [ 12 ].…”

“…In this study, we observed that developmental PCB exposure at the 1 mg/kg treatment group decreased anterior prostate collagen density in 6-week-old mouse offspring. Additionally, we have shown PCBs can lead to decreased collagen density in the bladder of developmentally exposed mice but only at the 0.1 mg/kg treatment group and predominantly in female mice [ 25 ]. Together this adds to the growing body of evidence that dioxin, as well as PCBs, can interfere with the extracellular matrix in the bladder and the prostate in a dose and sex-dependent manner.…”

“…The impacts of PCBs in the lower urinary tract have only recently garnered study. It has been observed that PCBs alter bladder morphology in mice following in utero and lactational exposure, increasing bladder volume, nerve fiber density, and inflammatory cells within the bladder of juvenile 4-week-old mice in a sex- and dose-dependent manner [ 24 , 25 ]. Developmental PCB exposure also leads to alterations in voiding patterns in 6-week-old mouse offspring, mainly characterized as increased small spot voiding, more frequent voiding and increases in voiding pressure in a sex- and dose-dependent manner [ 12 ].…”

Guardians Under Siege: Exploring Pollution's effects on Human Immunity

“…PCBs are also capable of altering the physiological antiviral cellular response [86]. In an in vivo mouse model, PCB promoted an alteration of collagen in the female bladder compared to the male one, indicating an inflammatory event that results in the impairment of immune system functions [87]. Moreover, studies from PCB-exposed populations have revealed DNA methylation differences in CpG sites with effects in oestradiol CpG site sizes and affecting the immune system [88].…”

“…(in vivo and ex vivo) [86] DNA methylation differences in PCBexposed populations Human PBMCs (ex vivo) [87] PBDEs Liver, kidney, gut, and thyroid toxicity…”