Fig. 2.

Transcriptome profiling analysis. A: list of top upregulated genes in pubertal lungs illustrates sex differences in differentially expressed genes (DEG) in pubertal vs. prepubertal infected lungs on day 9. B: Venn diagram analysis showing number of shared and distinct DEGs in infected lung samples (day 9) compared with their age-group matched uninfected controls. C: upstream regulator analysis using Ingenuity IPA analysis of DEG lists shows marked enrichment of hormonal regulators, especially estrogen and related molecules in both females and males. This is manifest as increased z-scores for estrogen, β-estradiol, or the estrogen receptor 1 (ESR1) across the time course of infection. The analysis also showed negative z-scores for the estrogen receptor antagonist fulvestrant on days 6 and 9, a finding consistent with enhanced estrogenic signaling. In addition, IL-1 signaling was also prominently identified as activated in both sexes. D: top 10 upstream regulators in normal blood transcriptomes based on an analysis of pubertal vs. prepubertal DEGs from P25 vs. P35 males, females, or pooled samples show considerable overlap; ESR1 is also identified as an upstream regulator in pubertal male and female samples.