title: Sex differences in neonatal and young adult rat lower urinary tract function caused by bladder reduction.
abstract: BACKGROUND
  Pediatric urinary incontinence has been proposed as a cause for adult urinary incontinence, yet animal models mimic the findings of overactive bladder more closely than dysfunctional voiding. We used the bladder reduction (BR) model to study the effects of early external urethral sphincter (EUS) dysfunction on the maturation of lower urinary tract function in neonatal and young adult rats of both sexes.
  
  
  OBJECTIVE
  To determine long-term alterations in bladder and EUS function in young adult rats caused by neonatal BR.
  
  
  METHODS
  46 Sprague-Dawley rats underwent BR and 52 underwent sham surgery at 1 week of age. At 3, 6, and 9 weeks of life, cystometry was carried out, 8-OH-DPAT (serotonergic receptor agonist) and WAY 100,635 (serotonergic receptor antagonist) were administered intravenously. Pressure threshold (PT), volume threshold (VT), storage tonic AUC, contraction area under the curve (AUC), EUS burst amplitude and burst duration were measured at baseline and after administration of serotonergic agents.
  
  
  RESULTS
  PT increased in 3-week BR females compared with shams (31.1 vs. 22.7 cm H2O, p < 0.01), in conjunction with less efficient EUS emptying, as burst amplitude was suppressed (BR 0.04 vs. sham 0.07 mV, p < 0.05). VT subsequently increased in 9-week BR females compared with shams (0.81 vs. 0.36 mL, p < 0.05). Although 3-week BR males also experienced suppressed burst amplitude (BR 0.17 vs. sham 0.28 mV, p < 0.05), they showed no difference in PT at 3 weeks or VT at 9 weeks compared with sham males. The burst amplitude returned to normal in 6- and 9-week BR animals of both sexes, confirming a spontaneous recovery of EUS function over time. The thresholds for voiding in male rats are not as sensitive to early changes in EUS function compared with female rats. The response to serotonergic agents was identical between BR and sham animals. In the female animals, 8-OH-DPAT increased storage tonic AUC and burst duration, whereas in male animals, 8-OH-DPAT increased contraction AUC, burst amplitude, and burst duration. WAY 100,635 reversed the enhancements of EUS function caused by 8-OH-DPAT.
  
  
  CONCLUSIONS
  BR caused a temporary impairment of EUS emptying at 3 weeks of life, similar to dysfunctional voiding, while serotonergic agonists remained effective at enhancing EUS emptying in BR animals. Although EUS emptying spontaneously improved, the increase in VT in female young adult rats suggests that timely treatment of EUS dysfunction is required to decrease the risk of long-term bladder dysfunction.
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: China
authors.initials: C
authors.lastname: Chien
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, CA, USA; University of Southern California Institute of Urology, Keck Medicine of USC, Los Angeles, CA, USA.
authors.forename: Huiyi Harriet
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: hwu2@stanford.edu.
authors.forename: Hsi-Yang
authors.initials: HY
authors.lastname: Wu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D005500:Follow-Up Studies; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D014521:Urethra / Q000503:physiopathology*; D001743:Urinary Bladder / Q000503:physiopathology* / Q000601:surgery; D014549:Urinary Incontinence / Q000209:etiology / Q000503:physiopathology*; D014554:Urination / Q000502:physiology*
keywords: Bladder; External urethral sphincter; Neonate; Rat; Serotonin