Peterson Nelson T, Vezina Chad M
Molecular and Environmental Toxicology Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Toxics. 2022 Feb 16;10(2):89. doi: 10.3390/toxics10020089.
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.
下尿路功能障碍（LUTD）在老年男性中几乎普遍存在，给社会带来了巨大的身体、心理、社会和经济成本。虽然大量研究集中在该疾病的分子、遗传和表观遗传基础上，但很少有研究致力于环境化学物质对疾病发生、发展或严重程度的影响。尽管最近有一些研究表明男性LUTD可能起源于子宫内的化学物质暴露，但在毒理学研究中，它仍然是一个研究严重不足的终点。因此，我们将这篇综述献给那些将男性LUTD视为化学毒性研究新领域的毒理学家。我们重点关注男性以及作为主要研究模型的雄性小鼠的LUTD疾病过程。为了介绍疾病过程，我们描述了男性下尿路的生理学以及下尿路组织的细胞组成。我们讨论了已知和疑似的男性LUTD机制，以及通过这些机制导致LUTD的环境化学物质实例。我们还描述了LUTD的小鼠模型以及诊断、表征和量化男性和小鼠LUTD的终点指标。
