AUA2023 TAKE HOME MESSAGES Basic Science (Benign)

By: Douglas Strand, PhD, University of Texas Southwestern Medical Center, Dallas | Posted on: 30 Aug 2023

Basic science in benign urology broadly includes bladder and pelvic pain, benign prostatic hyperplasia (BPH) and lower urinary tract dysfunction, female pelvic medicine, infertility, and stone disease. There was a strong emphasis on cellular pathogenesis in the 2023 program, including the development of new mouse models to pinpoint the cell type(s) contributing to bladder pain as well as single cell analyses of bladder, prostate, and kidney inflammation in development and disease.

In a moderated poster session on Infertility Basic Research and Pathophysiology, Katherine Campbell and colleagues at the University of Miami performed a microbiome analysis of men with nonobstructive azoospermia compared to fertile controls (MP01-07). The results demonstrated a decrease in seminal microbiome diversity and support the presence of a testicular microbiome that could be leveraged to guide treatment decision making.

Optogenetic and chemogenetic approaches in animal models are revealing new roles of peripheral (urothelial cells, sensory ganglia satellite glial cells) and central (hippocampus, rostroventral medulla) mechanisms in the development and persistence of chronic pelvic pain. In the Basic Science Symposium on New Developments in Understanding and Treating Pelvic Pain, Aaron Mickle, PhD, from the University of Florida presented a new optogenetic mouse model in which the urothelium could be directly stimulated with blue light. These data demonstrated that the urothelium is not nociceptive and its ability to affect bladder pressure is partially dependent on the P2X receptor.

In Session 2 of the Society of Basic Urologic Research Symposium, Nicholas Steers, PhD, from Columbia University presented a study of leukocytes in bladder development and induced urinary tract infection. A combination of 27 cell surface markers was used to identify leukocytes by flow cytometry and showed that a distinct population of Siglec F-positive macrophages are lost during urinary tract infection. Follow-up studies will determine whether these macrophages are carrying antigens to local lymph nodes to prime the immune response, which could lead to the development of vaccines for bladder infection.

In the same session, Renee Vickman, PhD, and colleagues from Northshore University showed that patients on a tumor necrosis factor α inhibitor for unrelated autoimmune disease displayed reduced prostate volume with a corresponding reduction in prostate macrophages. In addition, single-cell RNA sequencing of leukocytes in BPH specimens showed that a particular type of resident macrophage was associated with worse symptoms. In a moderated poster during the session on BPH epidemiology (MP24), Ra’ad Al-Faouri, MD, and colleagues at Beth Israel Deaconess Medical Center presented a similar electronic health record study of over 1 million men and found 634 men with serial pelvic imaging that were being treated with a tumor necrosis factor α inhibitor. After various exclusions, they found about 200 men who had imaging before and after treatment. These were typically younger men with smaller prostates, but a significant decrease in prostate volume and growth rate was observed. These are the first data to causally link prostate growth and inflammation.

During a moderated poster on Stone Disease Basic Research and Pathophysiology, Heiko Yang, MD, PhD, and colleagues at the University of California San Francisco used single-nuclear RNA-sequencing on human patients with Randall’s plaques and found that a tissue resident macrophage was associated with the plaque formation (MP05-02). They are currently pursuing how the presence of macrophages drives the initiation of kidney stones.

Ilaha Isali, MD, and colleagues from Case Western Reserve presented a moderated poster (MP03-02) showing that M2 macrophages harvested from rat bone marrow by flow cytometry and seeded into small collagen meshes can reduce MMP-9 while increasing TIMP-1. This could indicate a mechanism for limiting collagen breakdown associated with the development of stress urinary incontinence.

Finally, in a moderated poster session on Bladder and Urethra Anatomy, Physiology and Pharmacology, Ramy Goueli, MD, and colleagues from the University of Texas Southwestern Medical Center used single-cell RNA sequencing to create a cellular atlas of normal adult human female urethra from young organ donors (MP60-14). They verified by immunostaining that the female urethra and para-urethral ducts (Skene’s glands) are composed of the same hillock, club, and neuroendocrine epithelial cell types found in the prostatic urethra and proximal ducts of males (MP60-14). The identification of club cells in female urethra could yield new insight into the regulation of infection, inflammation, and obstruction.