Multi-species, Multi-tissue Meta-analysis of Bisphenol A Transcriptome Studies Reveals Species-and Tissue-specific Molecular Perturbations
- Author(s): Crymes, Anthony
- Advisor(s): Yang, Xia
- Collins, Michael
- et al.
The potential health impact of Bisphenol A (BPA) exposure remains a hotly debated issue. To explore the molecular actions of BPA in a data-driven manner, which may inform on pathway perturbations and health consequences, a systematic analysis of publicly available transcriptomic data was conducted. Species- and tissue-specific differential gene expression, biological pathways and processes, as well as transcriptional were reviewed across 19 datasets of BPA exposed tissues from rat, mouse, and human studies. A comparison of the data within and between species or tissues was conducted, revealing tissue-/species-specific molecular perturbation such as IL7 in human uterine tissue, or Wnt4 in mouse testis, or Tgfbr2 in rat breast tissues in response to exposure to BPA. In addition to such unique annotations, there were a few responses that were shared between tissues and between species such as common CYP26b1 or ALDH1a7 gene dysregulation, oxidative stress and insulin sensitivity related pathways in liver, and cytokine receptor activity in breast tissue, with differentially regulated genes such as IL1A being common across species that may point to a more conserved molecular response to BPA. In general, our results not only demonstrate complex species- and tissue-specific molecular activities of BPA, but also highlight some consistent transcription factors like SUZ12 and other PcG associated transcription factors as potential BPA targets across tissues and species. It is also apparent that there is a need for more comprehensive and systematic molecular investigations of BPA to better understand its mechanisms of action.