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

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.

• Publication year

  2016

• Venue

  Biology of Sex Differences

• Publication date

  2016-01-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s13293-016-0062-1PMID 26823967PMCID 4730611
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Case-Control Study

  2020cited by this paper
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  2015cited by this paper
• Interstitial cystitis: epidemiology, pathophysiology, and clinical presentation.

  2014cited by this paper
• Challenges and current evidence on the management of bladder pain syndrome

  2014cited by this paper
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  2014cited by this paper
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  2013cited by this paper
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  2013cited by this paper
• Stress in the adult rat exacerbates muscle pain induced by early-life stress.

  2013cited by this paper
• Water avoidance stress results in an altered voiding phenotype in male mice

  2012cited by this paper
• Bladder pain syndrome.

  2011influential reference
• Childhood sexual trauma in women with interstitial cystitis/bladder pain syndrome: a case control study.

  2011cited by this paper
• Social stress in mice induces voiding dysfunction and bladder wall remodeling.

  2009cited by this paper
• Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal.

  2008cited by this paper
• Dysfunctional nurturing behavior in rat dams with limited access to nesting material: a clinically relevant model for early-life stress.

  2008cited by this paper
• Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome.

  2007cited by this paper
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  2007cited by this paper
• Long‐term colonic hypersensitivity in adult rats induced by neonatal unpredictable vs predictable shock

  2007cited by this paper
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  2007cited by this paper
• Maternal Separation in Rats Leads to Anxiety-Like Behavior and a Blunted ACTH Response and Altered Neurotransmitter Levels in Response to a Subsequent Stressor

  2004cited by this paper
• Corticosterone influences on Mammalian neonatal sensitive-period learning.

  2004cited by this paper
• Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases

  2004cited by this paper
• Comorbidity of interstitial cystitis with other unexplained clinical conditions.

  2004cited by this paper
• Estrous influences on micturition thresholds of the female rat before and after bladder inflammation.

  2002cited by this paper
• Endogenous opioids and their role in odor preference acquisition and consolidation following odor-shock conditioning in infant rats.

  2001cited by this paper
• Neurophysiology: Good memories of bad events in infancy

  2000influential reference
• Long-term behavioral and neuroendocrine adaptations to adverse early experience.

  2000cited by this paper
• Increased pituitary activation following metyrapone administration in post-traumatic stress disorder.

  1996cited by this paper
• Abnormal corticosterone regulation in an immature rat model of continuous chronic stress.

  1996cited by this paper
• Changes in the categorization of appetitive and aversive events during postnatal development of the rat.

  1988influential reference
• Postnatal development of micturition reflex in rats.

  1986cited by this paper

• Low-intensity energy shock wave therapy modulates bladder function and anxiety-like behavior in maternal separation rats.

  2025cites this paper
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  2025cites this paper
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  2022influential citation
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  2021cites this paper
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  2018cites this paper
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  2018cites this paper
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  2017cites this paper