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Environ Mol Mutagen. 2017 Jan;58(1):4-18. doi: 10.1002/em.22071. Epub 2017 Jan 12.

Developmental programming: Interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep.

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Departments of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.
Department of Pediatrics, Texas Tech Health Sciences Permian Basin, Odessa, Texas.
Departments of Pediatrics, University of Michigan, Ann Arbor, Michigan.
Departments of Environmental Health, University of Cincinnati, Cincinnati, Ohio.
Departments of Pharmacology and Cell Biophysics, University of Cincinnati, Cincinnati, Ohio.


Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85-141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding. Environ. Mol. Mutagen. 58:4-18, 2017.


DOHAD; cardiometabolic diseases; endocrine disruptors; myocardium; obesity

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