Male Lower Urinary Tract Dysfunction: An Underrepresented Endpoint in Toxicology Research

Abstract

Lower urinary tract dysfunction (LUTD) is nearly ubiquitous in men of advancing age and exerts substantial physical, mental, social, and financial costs to society. While a large body of research is focused on the molecular, genetic, and epigenetic underpinnings of the disease, little research has been dedicated to the influence of environmental chemicals on disease initiation, progression, or severity. Despite a few recent studies indicating a potential developmental origin of male LUTD linked to chemical exposures in the womb, it remains a grossly understudied endpoint in toxicology research. Therefore, we direct this review to toxicologists who are considering male LUTD as a new aspect of chemical toxicity studies. We focus on the LUTD disease process in men, as well as in the male mouse as a leading research model. To introduce the disease process, we describe the physiology of the male lower urinary tract and the cellular composition of lower urinary tract tissues. We discuss known and suspected mechanisms of male LUTD and examples of environmental chemicals acting through these mechanisms to contribute to LUTD. We also describe mouse models of LUTD and endpoints to diagnose, characterize, and quantify LUTD in men and mice.

Establishment of new transurethral catheterization methods for male mice

“…Additionally, prostatitis predominantly affects middle-aged and elderly men. In fact, nearly 80% of prostate tissue biopsies in men over 60 reveal inflammation [ 18 , 19 ]. Given that most acute and chronic prostatitis models stem from transurethral catheterization [ 20 , 21 ], it accentuates the need to resolve the intubation challenge in male mice.…”

Lower Urinary Tract Symptoms in Depression: A Review

“…40, 3) There is a known association between depression and LUTS. 40,47,48,[50][51][52][54][55][56][57][58][59][60][61][62] The question we seek to answer is can depression actually cause LUTS? LUTS are present in at least 40% of men for extended periods of time which lead to significant impacts on HRQL.…”

“…This is further amplified when the condition that needs to be addressed is obvious to the patient but not those around them. 51,54,56,70,72,[77][78][79][84][85][86][87][88]93,94,[97][98][99][100]102,103,108,126,[128][129][130] This point is emphasized by the wealth of research on related (disabilities not outwardly visible) forms of disability such as neuropathic pain, MS, depression, myasthenia gravis etc. [91][92][93][94][95][96][97] There is a clear association between LUTS, and depression as addressed earlier, but is depression causing the LUTS, is it the other way around, or is there a confounding factor that we remain unaware of?…”

The Impact of Optic Nerve Disorders on Sleep Wake

“…With increasing age, outflow obstruction due to prostatic enlargement is common, with OSA increasing the risk of developing lower urinary tract dysfunction in males (721). Bladder and bowel symptoms are associated with anxiety and depression, which can also affect sleep (722,723), with depression and symptoms of overactive bladder found to negatively impact on each other (724).…”