Figure 2

The neonatal brain displays extensive sex bias in miR expression, which appears to result from both gonadal hormone and sex chromosomal regulation. In our previous studies, the expression of 240 miRs was assayed in postnatal day 2 whole brains from male and female mice. To determine the role of organizational estradiol in the male brain to program the miR environment, the aromatase inhibitor, formestane, was administered to males at this time and brain tissue compared with that from control males and females. Of these 240 miRs, 149 showed sex-biased expression. These 149 miRs were then further subdivided by: 1) their apparent responsiveness to estradiol, where detected sex differences were ameliorated by formestane treatment making them regulated at some level by gonadal hormones, 2) as likely attributable to X chromosome differences where females showed higher levels (likely due to X gene dosage) and showed no changes in males treated with formestane, or 3) uncategorized effect where the pattern of change did not fit either model of gonadal hormone effect or X-linkage. Of the 149 miRs with a basal sex difference, changes related to estradiol occurred for almost half of these genes (72 miRs), where aromatase inhibition dysmasculinized male expression patterns to look more like that of the females. An effect of sex chromosomes was estimated for 47 miRs, where aromatase inhibition had no affect on male expression. Analysis criteria found that neither regulatory mechanism could be attributed to 30 miRs. (Adapted from Morgan and Bale, 2011 [11]).