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Hints of altered microRNA expression in women exposed to EDCs


 

Dr. Shelley R. Ehrlich, assistant professor of pediatrics and environmental health at Cincinnati Children’s Hospital Medical Center Cincinnati Children's Hospital Medical Center

Dr. Shelley R. Ehrlich

Studies have shown that BPA and other environmental phenols can induce insulin resistance and metabolic dysfunction by acting on several endogenous pathways, including that those regulate energy and glucose metabolism. EDCs also have been found to be epigenetically toxic. In a landmark study in the agouti mouse model, maternal BPA exposure was shown to alter the animals’ epigenetic programming, leading to offspring that had yellow coats and were obese, rather than brown and small (Nutr Rev. 2008;66[Suppl 1]:S7-11). (The agouti mouse model has been used to study the impact of nutritional and environmental influences on the fetal epigenome; fur-color variation is correlated to epigenetic marks established early in development.)

Despite the mounting evidence for an association between BPA and type 2 diabetes, and despite the fact that the increased incidence of GDM in the past 20 years has mirrored the increasing use of EDCs, there has been a dearth of research examining the possible relationship between EDCs and GDM. The effects of BPA on GDM were identified as a knowledge gap by the National Institute of Environmental Health Sciences after a review of the literature from 2007 to 2013 (Environ Health Perspect. 2014 Aug:122[8]:775-86).

To understand the association between EDCs and GDM and the underlying mechanistic pathway of EDCs, we are conducting research that uses a growing body of evidence that suggests that environmental toxins are involved in the control of microRNA (miRNA) expression in trophoblast cells.

MiRNA, a single-stranded, short, noncoding RNA that is involved in posttranslational gene expression, can be packaged along with other signaling molecules inside extracellular vesicles in the placenta called exosomes. These exosomes appear to be shed from the placenta into the maternal circulation as early as 6-7 weeks into pregnancy. Once released into the maternal circulation, research has shown that the exosomes can target and reprogram other cells via the transfer of noncoding miRNAs, thereby changing the gene expression in these cells.

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