title: Sexually dimorphic effects of early life stress in rat pups on urinary bladder detrusor muscle contractility in adulthood.
abstract: 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.
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK USA.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Mohammadi
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK USA.
authors.forename: Dawn K
authors.initials: DK
authors.lastname: Prusator
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK USA.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Healing
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK USA ; Department of Urology, University of Oklahoma Health Science Center, Oklahoma City, OK USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Hurst
authors.affiliation: Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK USA ; Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK USA.
authors.forename: Rheal A
authors.initials: RA
authors.lastname: Towner
authors.affiliation: Department of Urology, University of Oklahoma Health Science Center, Oklahoma City, OK USA.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Wisniewski
authors.affiliation: VA Medical Center, Oklahoma City, OK USA ; Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, OK USA ; Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK USA.
authors.forename: Beverley
authors.initials: B
authors.lastname: Greenwood-Van Meerveld
keywords: Early life stress; Females; Males; Painful bladder syndrome/interstitial cystitis; Rats; Sex differences; Urinary bladder
references.citation: BMC Urol. 2015 Mar 08;15:14
references.pmid: 25887525
references.citation: Am J Physiol Renal Physiol. 2007 Nov;293(5):F1461-7
references.pmid: 17715261
references.citation: Am J Physiol. 1986 May;250(5 Pt 2):R926-31
references.pmid: 3706578
references.citation: Eur Urol. 2008 Jan;53(1):60-7
references.pmid: 17900797
references.citation: J Cell Biol. 2004 Dec 20;167(6):1195-204
references.pmid: 15611339
references.citation: Neurogastroenterol Motil. 2007 Sep;19(9):761-8
references.pmid: 17727395
references.citation: Ann Diagn Pathol. 2013 Oct;17(5):403-7
references.pmid: 23732167
references.citation: Behav Neurosci. 2004 Apr;118(2):274-81
references.pmid: 15113251
references.citation: Neurourol Urodyn. 2007;26(2):296-301
references.pmid: 17061265
references.citation: Am J Physiol Regul Integr Comp Physiol. 2014 Oct 1;307(7):R893-900
references.pmid: 25100077
references.citation: Obstet Gynecol Clin North Am. 2014 Sep;41(3):385-95
references.pmid: 25155120
references.citation: Med Clin North Am. 2011 Jan;95(1):55-73
references.pmid: 21095411
references.citation: Pediatr Neurol. 1996 Sep;15(2):114-9
references.pmid: 8888044
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G849-56
references.pmid: 17110521
references.citation: Neurourol Urodyn. 2012 Sep;31(7):1185-9
references.pmid: 22473515
references.citation: Nature. 2000 Sep 7;407(6800):38-9
references.pmid: 10993064
references.citation: Biol Psychiatry. 2013 Nov 1;74(9):688-95
references.pmid: 23706525
references.citation: Dev Psychobiol. 2001 Nov;39(3):188-98
references.pmid: 11745312
references.citation: Neurourol Urodyn. 2014 Nov;33(8):1193-201
references.pmid: 23946107
references.citation: Neuroscience. 2008 Jun 26;154(3):1132-42
references.pmid: 18501521
references.citation: Am J Physiol Renal Physiol. 2009 Oct;297(4):F1101-8
references.pmid: 19587139
references.citation: Psychoneuroendocrinology. 1996 Jan;21(1):1-16
references.pmid: 8778898
references.citation: Prog Brain Res. 2000;122:81-103
references.pmid: 10737052
references.citation: Can Urol Assoc J. 2011 Dec;5(6):410-5
references.pmid: 22154637
references.citation: J Urol. 2004 Oct;172(4 Pt 1):1242-8
references.pmid: 15371816
references.citation: J Pain. 2013 Mar;14 (3):270-80
references.pmid: 23348370
references.citation: Am J Physiol Regul Integr Comp Physiol. 2002 Jan;282(1):R289-94
references.pmid: 11742850
references.citation: Metab Brain Dis. 2004 Jun;19(1-2):3-14
references.pmid: 15214501
references.citation: Dev Psychobiol. 1988 Jan;21(1):25-42
references.pmid: 3338626