Conditions during fetal development influence health and disease in adulthood, especially during critical windows of organogenesis. Fetal exposure to the endocrine disrupting chemical, Bisphenol A ( ) affects the development of multiple organ systems in rodents and monkeys. However, effects of exposure on cardiac development have not been assessed. With evidence that maternal is transplacentally delivered to the developing fetus, it becomes imperative to examine the physiological consequences of gestational exposure during primate development. Herein, we evaluate the effects of daily, oral exposure of pregnant rhesus monkeys (Macaca mulatta) on the fetal heart transcriptome. Pregnant monkeys were given daily oral doses (400 Aug/kg body weight) of during early (50-100 A+- 2 days post conception, dpc) or late (100 A+- 2 dpc -- term), gestation. At the end of treatment, fetal heart tissues were collected and chamber specific transcriptome expression was assessed using genome-wide microarray. Quantitative real-time PCR was conducted on select genes and ventricular tissue glycogen content was quantified. Our results show that exposure alters transcription of genes that are recognized for their role in cardiac pathophysiologies. Importantly, myosin heavy chain, cardiac isoform alpha (Myh6) was down-regulated in the left ventricle, and 'A Disintegrin and Metalloprotease 12 ', long isoform (Adam12-l) was up-regulated in both ventricles, and the right atrium of the heart in exposed fetuses. induced alteration of these genes supports the hypothesis that exposure to during fetal development may impact cardiovascular fitness. Our results intensify concerns about the role of in the genesis of human metabolic and cardiovascular diseases.
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This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $900 million in funding from the federal government.