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

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.