Sexually dimorphic effects of early life stress in rat pups on urinary bladder detrusor muscle contractility in adulthood.

Dawn K. Prusator,Eleanor Healing,Beverley Greenwood-Van Meerveld,Robert Hurst,Amy B. Wisniewski,Rheal A. Towner,Ehsan Mohammadi

doi:10.1186/s13293-016-0062-1

Abstract

BackgroundPainful bladder syndrome/interstitial cystitis (PBS/IC) is a chronic disorder that is commonly seen in women who report a history of adversity in early life. Here, we test the hypothesis that early life stress (ELS) induces sexually dimorphic abnormalities in urinary bladder smooth muscle function in adulthood.MethodsMale and female rat pups were conditioned on postnatal (PN) days 8–12 with either a “predictable or “unpredictable” odor-shock, or odor only control treatment. In adulthood, urinary bladder function was assessed in vivo via urine spot analysis and in vitro via contractile responses to electrical field stimulation (EFS) and membrane depolarization with potassium chloride (KCl).ResultsIn adulthood, we found that female rats exposed to unpredictable ELS showed a significant (p < 0.05) increase in urine voiding volume compared to predictable ELS or controls. We also found that detrusor muscle contractile responses to EFS were significantly (p < 0.001) decreased following unpredictable ELS in adult female rats compared to the predictable ELS or controls. In male rats exposed to ELS, there was no difference in voiding volume or EFS-induced contractility between groups. In adulthood, the myogenic smooth muscle response to KCl was not significantly different between groups. Histological analysis from adult female and male rats revealed no differences in the appearance of the urinary bladder in rats exposed to ELS.ConclusionsIn summary, our findings provide evidence to support abnormalities in the nerve-mediated contractile responses of the detrusor smooth muscle in adult female rats following ELS. We speculate that these sexually dimorphic alterations in urinary bladder function may account, at least in part, for the female predominance of PBS/IC.

Highlights

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a chronic disorder that is commonly seen in women who report a history of adversity in early life
Additional evidence suggests that PBS/IC is more frequently reported in patients with a history of early life stress (ELS) such as neglect or abuse during childhood [11]; despite these recent advances, there are to our knowledge no studies examining the sex-specific effects of neonatal stress on urinary bladder muscle function in adulthood
Y-maze testing revealed a significant effect of treatment on odor choice (F(2,76) = 78.51, p < 0.0001) wherein animals in the predictable group showed a significant preference for the peppermint odor on the Y-maze test compared to animals who experienced unpredictable ELS (p < 0.0001) or odor only controls (p < 0.0001)

Summary

Introduction

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a chronic disorder that is commonly seen in women who report a history of adversity in early life. We test the hypothesis that early life stress (ELS) induces sexually dimorphic abnormalities in urinary bladder smooth muscle function in adulthood. Additional evidence suggests that PBS/IC is more frequently reported in patients with a history of early life stress (ELS) such as neglect or abuse during childhood [11]; despite these recent advances, there are to our knowledge no studies examining the sex-specific effects of neonatal stress on urinary bladder muscle function in adulthood. The current study tests the hypothesis that ELS induces abnormalities in urinary bladder function and detrusor muscle contractility in adulthood in a sex-dependent manner

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