Title: The influence of intermittent hypoxia, obesity, and diabetes on male genitourinary anatomy and voiding physiology.

Authors: Abler, Lisa L; O'Driscoll, Chelsea A; Colopy, Sara A; Stietz, Kimberly P Keil; Wang, Peiqing; Wang, Zunyi; Hartmann, Faye; Crader-Smith, Stephanie M; Oellete, Jonathan N; Mehta, Vatsal; Oakes, Steven R; Grimes, Matthew D; Mitchell, Gordon S; Baan, Mieke; Gallagher, Shannon J; Davis, Dawn B; Kimple, Michelle E; Bjorling, Dale E; Watters, Jyoti J; Vezina, Chad M

Published In Am J Physiol Renal Physiol, (2021 Jul 01)

Abstract: We used male BTBR mice carrying the Lepob mutation, which are subject to severe and progressive obesity and diabetes beginning at 6 wk of age, to examine the influence of one specific manifestation of sleep apnea, intermittent hypoxia (IH), on male urinary voiding physiology and genitourinary anatomy. A custom device was used to deliver continuous normoxia (control) or IH to wild-type and Lepob/ob (mutant) mice for 2 wk. IH was delivered during the 12-h inactive (light) period in the form of 90 s of 6% O2 followed by 90 s of room air. Continuous room air was delivered during the 12-h active (dark) period. We then evaluated genitourinary anatomy and physiology. As expected for the type 2 diabetes phenotype, mutant mice consumed more food and water, weighed more, and voided more frequently and in larger urine volumes. They also had larger bladder volumes but smaller prostates, seminal vesicles, and urethras than wild-type mice. IH decreased food consumption and increased bladder relative weight independent of genotype and increased urine glucose concentration in mutant mice. When evaluated based on genotype (normoxia + IH), the incidence of pathogenic bacteriuria was greater in mutant mice than in wild-type mice, and among mice exposed to IH, bacteriuria incidence was greater in mutant mice than in wild-type mice. We conclude that IH exposure and type 2 diabetes can act independently and together to modify male mouse urinary function. NEW & NOTEWORTHY Metabolic syndrome and obstructive sleep apnea are common in aging men, and both have been linked to urinary voiding dysfunction. Here, we show that metabolic syndrome and intermittent hypoxia (a manifestation of sleep apnea) have individual and combined influences on voiding function and urogenital anatomy in male mice.

PubMed ID: 34121451

MeSH Terms: Animals; Diabetes Mellitus, Type 2/genetics; Diabetes Mellitus, Type 2/metabolism*; Disease Models, Animal; Hypoxia/genetics; Hypoxia/metabolism*; Insulin Resistance/physiology; Liver/metabolism; Male; Metabolic Syndrome/genetics; Metabolic Syndrome/metabolism*; Mice; Obesity/genetics; Obesity/metabolism*