Presentations

Abstract

Introduction: Benign prostatic hyperplasia (BPH) is the enlargement of epithelium and stroma in the transitional zone of the prostate gland. BPH is common in men over the age of 50, and prevalence increases to over 80% by age 70. Prostate enlargement can cause urethral obstruction and resistance and an increase in lower urinary tract symptoms (LUTS) which include urinary urgency, frequency, and incomplete emptying of the bladder. Our prior study showed a significant increase in lipids in human BPH specimens. We also showed upregulation of genes in the lipid synthesis pathway in a mouse model of BPH induced by steroid hormone imbalance. Lipid accumulation in other tissues, such as the liver and vascular connective tissue, triggers inflammation and fibrosis. Risk factors for BPH include diet and hormonal changes, with the most influential factor being age. Therefore, we hypothesize that aging is correlated to an increase in prostatic lipids, inflammation and urinary dysfunction.

Methods: Mice of varying ages (young, mature, aged) underwent a 6-hour uroflow study to measure the total number of voids, the average void mass, and the total void mass. Mice were then euthanized, and the four lobes of the prostate were collected to prepare frozen or formalin-fixed paraffin-embedded slides. Bladder dimensions were also measured. Oil Red O (ORO) staining was performed with the frozen tissue slides to detect lipids and immunohistochemistry was performed to analyze the expression of Fatty Acid Synthase (FASN) and immune cells via CD45 expression. Images were taken on a Mantra Quantitative Pathology Workstation and optical density, or the total number of CD45-positive cells, was quantified with Inform software. Differences between age groups was determined with Kruskal-Wallis and Dunn's multiple comparison test, with statistical significance defined as p<0.05. Results are reported as mean ± SEM.

Results: Via uroflow analysis, aged mice demonstrated a 3-fold increase in average void mass (p=0.0050) and a 2-fold increase in total void mass (p=0.0099) compared to young mice. Bladder volume did not show a significant difference between the different age groups. ORO yielded a 10-fold increase in the percent of lipids in the ventral prostate in the aged mice over the mature mice (p=0.0068). FASN expression was not significantly elevated in the ventral and anterior lobes.

Conclusion: Preliminary results suggested an age-related increase in lipid accumulation in the prostate. Although no significant differences were observed in bladder volume, the increase in void mass suggested that differences in prostate histology might be the cause of the urinary dysfunction seen in our experiment. While lipid accumulation may contribute to these urinary changes, the initial FASN analysis has not demonstrated significant differences between our populations and therefore may not be as important for lipid synthesis in the aging prostate as originally hypothesized. Further investigation will focus on RNA-sequencing of the collected tissues to determine differentially expressed genes in the de novo lipid synthesis pathway in efforts to further understand the mechanism of lipid accumulation in the prostate during the progression of BPH.