title: Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol.
abstract: Aging men are susceptible to developing lower urinary tract symptoms, but the underlying etiology is unknown and the influence of dietary and environmental factors on them is unclear. We tested whether a folic acid-enriched diet changed urinary tract physiology and biology in control male mice and male mice with urinary dysfunction induced by exogenous testosterone and estradiol (T+E2), which mimics changing hormone levels in aging humans. T+E2 treatment increased mouse urine output, time between voiding events, and bladder capacity and compliance. Consumption of a folic acid-enriched diet moderated these changes without decreasing prostate wet weight or threshold voiding pressure. One potential mechanism for these changes involves water balance. T+E2 treatment increases plasma concentrations of anti-diuretic hormone, which is offset at least in part by a folic acid-enriched diet. Another potential mechanism involves neural control of micturition. The folic acid-enriched diet, fed to T+E2-treated mice, increased voiding frequency in response to intravesicular capsaicin infusion and increased mRNA abundance of the capsaicin-sensitive cation channel transient receptor potential vanilloid subfamily member 1 (Trpv1) in L6 and S1 dorsal root ganglia (DRG) neurons. T+E2 treatment and a folic acid-enriched diet also modified DNA methylation, which is capable of altering gene expression. We found the enriched diet increased global DNA methylation in dorsal and ventral prostate and L6 and S1 DRG. Our results are consistent with folic acid acting to slow or reverse T+E2-mediated alteration in urinary function in part by normalizing water balance and enhancing or preserving afferent neuronal function.
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin;
authors: Kimberly P
authors: KP
authors: Keil
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin;
authors: Lisa L
authors: LL
authors: Abler
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin;
authors: Helene M
authors: HM
authors: Altmann
authors: Department of Surgical Sciences, University of Wisconsin-Madison, Madison, Wisconsin;
authors: Zunyi
authors: Z
authors: Wang
authors: Department of Surgical Sciences, University of Wisconsin-Madison, Madison, Wisconsin;
authors: Peiqing
authors: P
authors: Wang
authors: Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin; Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin; and George M. O'Brien Center of Benign Urology, University of Wisconsin-Madison, Madison, Wisconsin.
authors: William A
authors: WA
authors: Ricke
authors: Department of Surgical Sciences, University of Wisconsin-Madison, Madison, Wisconsin; Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin; George M. O'Brien Center of Benign Urology, University of Wisconsin-Madison, Madison, Wisconsin.
authors: Dale E
authors: DE
authors: Bjorling
authors: Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin; Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin; and George M. O'Brien Center of Benign Urology, University of Wisconsin-Madison, Madison, Wisconsin cmvezina@wisc.edu.
authors: Chad M
authors: CM
authors: Vezina
mesh_terms: D000821:Animal Feed; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D004032:Diet; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005492:Folic Acid / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D059411:Lower Urinary Tract Symptoms / Q000188:drug therapy*; D008297:Male; D008810:Mice, Inbred C57BL; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D014553:Urinary Tract Physiological Phenomena / Q000187:drug effects*
chemical_list: D013739:Testosterone; D004958:Estradiol; D005492:Folic Acid; D002211:Capsaicin
keywords: cystometry; epigenetics; folic acid; mouse model; voiding