# PCB Exposure in Adult Male Mice Reduces Proliferating Cells in the Prostate but Minimally Alters Voiding

## TL;DR

Exposure to PCBs in adult male mice slightly reduces prostate cell proliferation but has minimal effects on bladder function.

## Contribution

The study reveals that adult PCB exposure affects prostate cell proliferation but not voiding function in mice.

## Key findings

- PCB exposure reduced Ki67-positive proliferating cells in the prostate at 1 mg/kg/d.
- Voiding function was minimally altered, with only a reduction in void duration at 6 mg/kg/d.
- No changes were observed in prostate weight or smooth muscle thickness.

## Abstract

Lower urinary tract dysfunction (LUTD) is a multifactorial disease process that encompasses diverse symptoms ranging from issues with storage and sensation to impaired emptying of the bladder. Furthermore, symptoms tend to worsen with age and other comorbidities and in men can also be influenced by changes to the prostate, making diagnosis and treatment difficult to manage. Environmental factors are thought to contribute to disease risk. In mice, previous work has found that developmental exposure to polychlorinated biphenyls (PCBs) is capable of altering voiding function in offspring. However, the effects of PCB exposure in adulthood instead of development are not well known. Whether changes in voiding are a consequence of early or later life exposures remains an important area of study, as environmental chemicals and exposures can occur across the lifespan and can be mitigated. Here, we test whether PCB exposure in adulthood alters voiding or prostate morphology in male mice. C57Bl/6J adult male mice were exposed to the human-relevant MARBLES PCB mixture (0, 0.1, 1, and 6 mg/kg/d) orally daily for two months. Lower urinary tract function was then assessed through urodynamic testing including void spot assay, uroflowmetry, and anesthetized cystometry. Prostate lobes were collected for histology. The only change to voiding function was a reduction in void duration in the 6 versus 1 mg/kg/d PCB group but not to the vehicle control. Prostate, seminal vesicle, and testes wet weights were unchanged. However, PCB exposure reduced the number of Ki67-positive proliferating cells in the anterior and ventral prostate lobes only at the 1 mg/kg/d dose, with no change to caspase 3-positive cells or smooth muscle thickness. Together, these data indicate that 2-month exposure to PCBs in adult mice has little impact on voiding but is a sufficient exposure to produce changes in cell proliferation in the prostate. The mechanistic impacts of these changes remains to be investigated but could help better understand individual risk for LUTD.