Mouse urothelial genes associated with voiding behavior changes after ovariectomy and bladder lipopolysaccharide exposure

• Published in: Neurourology and urodynamics 2018-11, Vol.37 (8), p.2398-2405
• Main Authors: Acevedo‐Alvarez, Marian, Yeh, Judy, Alvarez‐Lugo, Lery, Lu, Ming, Sukumar, Nitin, Hill, Warren G., Chai, Toby C.
• Format: Article
• Language: English
• Subjects: Adenosylmethionine; Adenosylmethionine decarboxylase; Cystitis; Cytokines; DNA microarrays; Gene expression; GTP cyclohydrolase; Guanosine triphosphate; host response; Hybridization; Interleukin 6; Lipopolysaccharides; Ovariectomy; overactive bladder; Rodents; Surgery; Urinary tract; Urinary tract infections; Urination; urothelium; Zinc finger proteins
• ISSN: 0733-2467; 1520-6777
• DOI: 10.1002/nau.23592

Aims Symptoms from overactive bladder (OAB) and cystitis secondary to urinary tract infection (UTI) can be similar in post‐menopausal women. Effects of ovariectomy (OVX) on voiding behavior after lipopolysaccharide (LPS) intravesical exposure (surrogate for cystitis) in mice were measured. Urothelial genes associated with micturition changes were identified. Methods Female C57BL6/J mice underwent OVX or sham surgeries (n = 10 for each). Voiding spot assays (VSA) were performed prior to surgery, 4 weeks post‐surgery, and each time after 3 consecutive days of transurethral instillation of LPS. In another experiment, mice underwent either sham (n = 9) or OVX (n = 9) surgeries. Urothelial RNAs were collected 4 weeks post‐surgery, day 1 and day 3 after LPS instillation. Mouse Gene 2.0 ST Arrays (entire 34 K transcripts) were used for microarray hybridization. A set of criteria was utilized to identify gene expression changes that mimicked voiding behavior changes. Results Three days after LPS exposure, OVX mice persisted with overactive whereas sham mice normalized voiding behavior. Nine urothelial paralleling voiding behavior changes were identified: IL6 (interleukin 6), IL6rα (Interleukin 6 receptor α), Ptgs2 (Prostaglandin‐endoperoxide synthase 2 or COX‐2), Ereg (epiregulin), Dusp6 (dual specificity phosphatase 6), Zfp948 (zinc finger protein 948), Zfp52 (Zinc finger protein 52), Gch1 (GTP cyclohydrolase 1), and Amd (S‐adenosylmethionine decarboxylase). Three other genes, coding unknown proteins, were also identified: GM12840, GM23134, and GM26809. Conclusions OVX mice persisted with increased voiding frequency after LPS. Urothelial genes that could mediate this voiding behavior include IL6, COX‐2, and S‐adenosylmethionine decarboxylase.