Dysregulation of DNA methylation and expression of imprinted genes in mouse placentas of fetal growth restriction induced by maternal cadmium exposure. (1st September 2017)

• Record Type: Journal Article
• Authors: Xu, Peng; Wu, Zhongqiang; Yang, Weiwei; Wang, Lan
• Is Part Of: Toxicology. Volume 390(2017)
• Page Start: 109
• Page End: 116
• Publication Date: 2017-09-01
• Subjects: Cd cadmium -- FGR fetal growth restriction -- qPCR quantitative real-time PCR -- Slc38a4 solute carrier family 38 member 4 -- Grb10 Growth factor receptor-bound protein 10 -- Cdkn1c Cyclin dependent kinase inhibitor 1c -- IGF2R Insulin-like growth factor 2 receptor -- Phlda2 Pleckstrin homology like domain family A member 2 -- Peg10 Paternally expressed gene 10 -- Gpc3 Glypican 3 -- Chm Choroidermia -- Sgce Sarcoglycan epsilon -- Plagl1 PLAG1 like zinc finger 1 -- Dlk1 Delta like non-canonical Notch ligand 1 -- Esx1 ESX homeobox 1; Fetal growth restriction -- Placenta -- Imprinted gene -- DNA methylation -- Cadmium; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2017.08.003
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: FGR in Cd-treated mice is linked to a significant increase of Cdkn1c and a significant decrease of Peg10 in Cd-exposed placentas. The differential expression levels of Cdkn1c and Peg10 may be caused by the DNA methylation modification of the promoter region of these genes. The differential expression level of Cdkn1c is correlated with the DNA methylation changes of the site 2 but not site 1 of its promoter region. Abstract: 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.