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

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BACKGROUND: 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. Here, we test the hypothesis that early life stress (ELS) induces sexually dimorphic abnormalities in urinary bladder smooth muscle function in adulthood. METHODS: Male 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). RESULTS: In 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. CONCLUSIONS: In 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.




Mohammadi, E., Prusator, D. K., Healing, E., Hurst, R., Towner, R. A., Wisniewski, A. B., & Greenwood-Van Meerveld, B. (2016). Sexually dimorphic effects of early life stress in rat pups on urinary bladder detrusor muscle contractility in adulthood. Biology of Sex Differences, 7(1).

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