Developmental Programming: adipose depot-specific regulation of non-coding RNAs and their relation to coding RNA expression in prenatal testosterone and prenatal bisphenol-A -treated female sheep
John Dou*, Soundara Viveka Thangaraj*, Muraly Puttabyatappa, Venkateswaran Ramamoorthi Elangovan, Kelly Bakulski†, Vasantha Padmanabhan1†
*Co-first authors †Share equal credit
Dou J, Thangaraj SV, Puttabyatappa M, Elangovan VR, Bakulski KM*, Padmanabhan V*. Developmental Programming: adipose depot-specific regulation of non-coding RNAs and their relation to coding RNA expression in prenatal testosterone and prenatal bisphenol-A -treated female sheep. Molecular and Cellular Endocrinology. In press
Inappropriate developmental exposure to steroids is linked to metabolic disorders. Prenatal testosterone excess or bisphenol A (BPA, an environmental estrogen mimic) leads to insulin resistance and adipocyte disruptions in female. Adipocytes are key regulators of insulin sensitivity and tissue-specific differences in insulin sensitivity, coupled with adipose depot-specific changes in key mRNAs, were previously observed. We hypothesized that depot-specific changes in the non-coding RNA (ncRNA) regulators of gene expression would prevail to account for the direction of changes seen in mRNAs. Noncoding RNA (lncRNA, miRNA, snoRNA, snRNA) from various adipose depots of prenatal testosterone and BPA-treated animals were sequenced. Adipose depot-specific changes in the ncRNA that are consistent with the depot-specific mRNA expression in terms of directionality of changes and functional implications in insulin resistance, adipocyte differentiation and cardiac hypertrophy were found. Importantly, the adipose depot-specific ncRNA changes were model-specific that were mutually exclusive suggestive of different regulatory entry points in this regulation.
GEO: pending
Research reported in this publication was supported by Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (NIH) under award R01HD099096-02S1 and P01 HD44232, and National Institute of Environmental Health Sciences R01 ES016541, R01 ES 030374, and P30 ES017885. MP was supported via Ruth L. Kirschstein Institutional Training Grant T32 ES007062. TSV is a Cneter Scientist in M-LEEaD NIEHS Core Center P30 ES017885