title: Comparisons of chromosome Y-substituted mouse strains reveal that the male-specific chromosome modulates the effects of androgens on cardiac functions.
abstract: BACKGROUND
  The C57BL/6J.YA/Jmouse strain is a chromosome-substituted line where the original male-specific portion of chromosome Y (MSY) from C57BL/6J mice was substituted for that from A/J mice. In hearts from male C57BL/6J.YA/Jand C57BL/6J mice, orchidectomy (ORX) affected in a strictly strain-specific fashion the expression a subset of genes showing enrichment for functional categories, including that of circadian rhythms and cardiac contractility. We further tested whether: (1) there were strain-specific differences in cardiac circadian rhythms; (2) strain-dependent differences in the effects of ORX on contractility genes translated into differences in cardiac functions; and (3) differential contractility responses occurred preferentially at times when circadian rhythms also showed strain-specific differences.
  
  
  METHODS
  In hearts from the two above strains, we (1) profiled the expression levels of 15 circadian genes at 4-h intervals across a 24 h period; (2) tested the effects of either ORX or androgen replacement on expression of cardiac contractility genes, and that of ORX on myocardial functional reserve; and (3) verified whether the effects of MSY variants on cardiac contractility-related responses showed synchronicity with differences in circadian rhythms.
  
  
  RESULTS
  Among the 15 tested circadian genes, a subset of them were affected by strain (and thus the genetic origin of MSY), which interacted with the amplitude of their peak of maximal expression at 2:00 PM. At that same time-point, ORX decreased (and androgen supplementation increased) the expression of three contractility-related genes, and decreased myocardial relaxation reserve in C57BL/6J.YA/J, but not in C57BL/6J mice. These effects were not detected at 10:00 AM, i.e., at another time-point when circadian genes showed no strain-specific differences.
  
  
  CONCLUSIONS
  The results indicate that in mice, androgens have activational effects on cardiac circadian rhythms, contractile gene expression, and myocardial functional reserve. All effects occurred preferentially at the same time of the day, but varied as a function of the genetic origin of MSY. Androgens may therefore be necessary but not sufficient to impart male-specific characteristics to some particular cardiac functions, with genetic material from MSY being one other necessary factor to fully define their range of actions.
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM) and Dept of Medicine, Cardiovascular Biology Research Unit, Université de Montréal, 100 Pine Ave West, Montreal, QC H2W 1R7 Canada ; Present address: Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association, Robert-Rössle-Str. 10, D-13125 Berlin, Germany.
authors.forename: Samantha D
authors.initials: SD
authors.lastname: Praktiknjo
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM) and Dept of Medicine, Cardiovascular Biology Research Unit, Université de Montréal, 100 Pine Ave West, Montreal, QC H2W 1R7 Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Picard
authors.affiliation: Institut de recherches cliniques de Montréal (IRCM) and Dept of Medicine, Cardiovascular Biology Research Unit, Université de Montréal, 100 Pine Ave West, Montreal, QC H2W 1R7 Canada.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Deschepper
keywords: Androgens; Chromosome Y substituted mouse strains; Circadian genes; Circadian rhythms; Genetic variants; Heart; Male-specific portions of chromosome Y; Myocardial contractile reserve