1. 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.
- Author
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Dou, John, Thangaraj, Soundara Viveka, Puttabyatappa, Muraly, Elangovan, Venkateswaran Ramamoorthi, Bakulski, Kelly, and Padmanabhan, Vasantha
- Subjects
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GENE expression , *NON-coding RNA , *RNA regulation , *BISPHENOL A , *TESTOSTERONE , *ESTROGEN receptors , *ADIPOGENESIS - Abstract
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 lambs. Adipocytes are key regulators of insulin sensitivity. Metabolic tissue-specific differences in insulin sensitivity coupled with adipose depot-specific changes in key mRNAs, were previously observed with prenatal steroid exposure. We hypothesized that depot-specific changes in the non-coding RNA (ncRNA) - regulators of gene expression would account for the direction of changes seen in mRNAs. Non-coding 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 and mutually exclusive, suggestive of different regulatory entry points in this regulation. [Display omitted] • Prenatal testosterone (T) excess programs adipose depot-specific changes in ncRNA. • Prenatal T induced ECAT miRNA changes is consistent with its cardioprotective role. • Prenatal T induced VAT ncRNA changes link to metabolism regulating coding genes. • Prenatal bisphenol A (BPA) programmed ncRNA changes was specific to VAT not SAT. • ncRNA changes in pre-T and BPA models indicate different mechanisms of action. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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