BMC Genomics 2009, 10:150 http://www.biomedcentral.com/1471-2164/10/150 cRFmaeiaRsgaltNuelr-artACiteme5td8e7r)aBRnLTs/c6-rPJiCpantRsdoqCfu5aD7nd.tYxifiA3caa(tnei oditnhEseifro2fisn3tthyaecintabsthuaenmdha-enoacpreetsroaoftfeaddouflt Real-time RT-PCR quantifications of the abundance of mRNA transcripts of Ddx3 and Eif2s3y in the hearts of adult male C57BL/6J and C57.YA (either intact sham-operated of castrated). The figures repre- sent values obtained with samples from individual animals, scattered around the mean of the group. could not be explained on the basis of an insensitivity of cells from C57BL/6J-chrYA to androgens, because post- pubertal testosterone affected the expression of more genes in hearts from in C57BL/6J-chrYA than in that from C57BL/6J. Moreover, several cardiac genes responded to post-pubertal testosterone in a strict strain-selective man- ner. These findings provide possible mechanisms explain- ing how chrY may, in part via interference with androgen regulatory events, be linked to morphologic differences of cardiac cells of adult male mice. Of note, there are well- known differences in the manifestations of cardiovascular diseases between men and women [34,35]. Despite the important contributions of post-pubertal sex steroids, the latter do not account for all differences, and there is now evidence that genes present on sex chromosomes also play important roles as well [36]. In light of the current data, it becomes worth testing further to which extent: 1) chrY related associations can be explained in terms of modula- tion of the effects of androgens, and 2) chrY may partici- pate to male/female differences in cardiovascular diseases. Methods Experimental animals All procedures on animals were approved by the Institut de Recherches Cliniques de Montréal (IRCM) Institu- tional Animal Care Committee and conducted according to guidelines issued by the Canadian Council on Animal Care. All mice were obtained from The Jackson Laboratory (Bar Harbor, ME). In addition to the parental A/J and C57BL/6J strains, we used their respective chromosome- substitution strains (also known as consomic strains) A/J- chrYC57BL/6J/NaJ and C57BL/6J-chrYA/J/NaJ strains (previ- ously simply identified as A.YC57 and C57.YA). The latter corresponded to either A/J or C57BL/6J male mice whose chrY has been switched by inbreeding for that of the other strain [37]. To evaluate the effect of post-pubertal testo- sterone, all animals were operated between 3 and 4 weeks of age, with castration being performed in some mice to prevent the rise of testosterone that normally occurs at puberty, and sham-operated mice being used as controls. To evaluate the effects of testosterone replacement, all ani- mals were castrated between 3 and 4 weeks of age, and subcutaneous injections of either vehicle (i.e. vegetable oil) or testosterone cypionate (0.5 and 2 mg/kg) were per- formed 3 times per week between 8 and 12 weeks of age. CFRei5ga7ulB-rtLiem/69eJ aRnTd-PCC5R7.YquAatnatkiefincaattiodnisffeorfetnhtetaimbuensddaunrcinegodf emveRlNopAmternantscripts of Ddx3 and Eif2s3y in the hearts of intact male Real-time RT-PCR quantifications of the abundance of mRNA transcripts of Ddx3 and Eif2s3y in the hearts of intact male C57BL/6J and C57.YA taken at different times during development. The points represent means ± SD (n = 5). Page 8 of 11 (page number not for citation purposes)