BMC Genomics 2009, 10:150 http://www.biomedcentral.com/1471-2164/10/150 Background Chromosome Y (chrY) stands out from all other chromo- somes: it is comprised for most of its length of sequences that do not recombine (the so-called "male-specific part"), it contains many repetitive DNA sequences of unclear significance, and it harbors only a small number of active genes [1]. Genes from the male-specific part of chrY are clearly not essential for life, as demonstrated in female organisms. Besides Sry (the master gene in sex determination), most of what is known about the func- tions of other chrY genes relates to their effects on male reproductive and sex accessory organs [2-4]. Nonetheless, genetic variants of chrY have been shown to have an impact on functions unrelated to male reproductive biol- ogy, including the severity of experimental allergic encephalomyelitis in mice [5], the incidence of prostate cancer in humans [6,7], and several cardiovascular condi- tions such as hypertension and high plasma cholesterol in either humans or animal models [8-10]. The mechanism explaining these particular effects of chrY genes are still unclear, and cannot be explored by using classical genetic methods because chrY genes do not recombine. Recently, we have reported that chrY accounts for a large part of the genetic variance of the size of adult male heart muscle cells [i.e. cardiomyocytes (CMs)] isolated from mice derived from crosses between A/J and C57BL/6J [11]. In agreement with the linkage mapping results, we also found that when chrY from the parental strain C57BL/6J (ChrYC57) was substituted for that of A/J mice (ChrYA), CMs from the resulting "chromosome substitution" (or "consomic") C57BL/6J-chrYA strain (C57.YA) were smaller than that of their C57BL/6J counterparts. In reverse, when chrYA from A/J mice was substituted for that of chrYC57, CMs from the resulting A/J-chrYC57 strain (A.YC57) were larger than in their A/J counterparts. Since the only genetic differences in these unique animal models are those pos- sibly existing between C57BL/6J and C57.YA, we used these strains to further test whether, in addition to affect- ing the size of CMs, the origin of chrY could also be linked to differences in the profile of gene expression in the hearts of adult male mice. Moreover, since: 1) one of the most obvious consequences of chrY is to foster the devel- opment of male gonads and the production of testoster- one, and 2) there is preliminary evidence that chrY polymorphisms may interfere with some biologic effects of testosterone [10,12], we tested whether postpubertal testosterone could play a role in the differential morpho- logic and/or molecular effects of chrYC57 and chrYA on car- diac cells. Results and discussion In extension to our previous findings showing that CMs from strains carrying chrYC57 were larger than that from their counterparts carrying chrYA [11], we found that pre- pubertal castration (which prevents the increase in plasma testosterone that normally occurs at puberty) decreased the size of CMs in adult animals from strains carrying YC57 (i.e. C57BL/6J and A.YC57 mice), but not in their counter- parts carrying chrY from A/J (YA), i.e. A/J and C57.YA mice (Figure 1). The effect of castration (CX) was not the result of testosterone production being higher in C57BL/6J mice, as plasma testosterone in adult male C57BL/6J mice (2.5 ± 1.7 ng/ml) was in fact lower than in their A/J (10.8 ± 3.6) or C57.YA (9.6 ± 4.5) counterparts, this result being in agreement with another report showing that the levels of plasma testosterone are lower in male C57BL/6J mice than in several other mouse inbred strains [13]. Likewise, the abundance of androgen receptor mRNA and protein was similar in the hearts of all strains (not shown). How- ever, chronic treatment of mice that had been castrated at 3 weeks of age with 2 dosages of testosterone from 8 to 12 weeks of age increased the size of CMs of C57BL/6J in a dose-dependent fashion, but not in the consomic strain C57.YA (Figure 2). In contrast, testosterone also increased the size of CMs from consomic A.YC57 in a dose-depend- ent fashion, although we had found that cardiomyocytes from the parental A/J strain were not affected by CX. Alto- gether, these results showed that the difference in size of CMs from intact (sham-operated) C57BL/6J and C57.YA male mice resulted from the fact that cardiomyocytes from C57.YA were not sensitive to the hypertrophic effects of post-pubertal testosterone. We next compared the cardiac transcriptosomes of 4 sham-operated and 4 CX adult male mice from the C57BL/6J and C57.YA strains. The numbers of probes and corresponding genes showing differential expression between groups (selected on the basis of a FDR < 0.1) are summarized in Table 1. We found that the effects of post- pubertal testosterone and/or the origin of chrY affected the profile of cardiac gene expression in a manner that was SCFui5gr7fuaBrcLe/6a1Jr,eAa/oJ.YfCca57rdoiromCy5o7c.YyAtemsifcreom 12 week-old male A/J, Surface area of cardiomyocytes from 12 week-old male A/J, C57BL/6J, A/J.YC57 or C57.YA mice. All ani- mals have undergone surgery (either sham or castration) at 4 weeks of age. The figures represent values for individual ani- mals scattered around the mean value of the group. ***P < 0.001 vs. sham-operated. Page 2 of 11 (page number not for citation purposes)