Dysregulation of DNA methylation and expression of imprinted genes in mouse placentas of fetal growth restriction...

Cadmium (Cd) is one of the most toxic environmental pollutants that cause fetal malformation and growth restriction. However, the molecular mechanisms underlying maternal Cd toxicity on fetal growth remain largely unknown. Specifically, the expression profiles and the regulation mechanisms of the imprinted genes, have been poorly characterized in the etiology of Cd-induced fetal growth restriction (FGR). In the present study, 13 imprinted genes associated with the fetal growth and placenta development were selected and their expression patterns were examined in the Cd-exposed placentas. Quantitative real-time PCR and western blot results showed that the maternally expressed gene, Cyclin dependent kinase inhibitor 1c (Cdkn1c), and paternally expressed gene, Paternally expressed gene 10 (Peg10), were significantly upregulated and downregulated respectively in the Cd-exposed placentas when compared to the normal ones respectively. Moreover, data from bisulfate PCR demonstrated the changes of the methylation levels of the promoter regions of Cdkn1c and Peg10 in the Cd-exposed placentas. In addition, the expression profile of Cdkn1c was correlated with the methylation levels of site 2 (-837--692) but not site 1 (-389--185) of its promoter region. Therefore, our results suggest that changes of the DNA methylation levels of the promoter regions and the expression patterns of Cdkn1c and Peg10 may be involved in the etiology of Cd-induced fetal growth restriction.