Spina bifida in fetus is associated with an altered pattern of DNA methylation in placenta

Failure in closure of neural tube leads to neural tube defects (NTDs), which are among the most common symptoms of human birth defects. Although epigenetic status in placenta is linked to fetal development, the mechanism behind this remains unknown. Because of the importance of DNA methylation in gene function, we set to explore whether or not DNA methylation in human placenta is also linked to fetal NTDs. Here we show for the first time that alteration of DNA methylation in placenta is closely associated with the phenotypes of fetal spina bifida (Sb). We found that patterns of DNA methylation for genes in neurological system process were differentially altered in the Sb placenta. In particular, the transcription regulatory regions of TRIM26 and GANS were kept at the hypomethylation status in Sb placenta alone. Accordingly, the protein levels of TRIM26 and GNAS were significantly elevated only in the Sb placenta but not in the Sb-affected fetuses. In cellular model of CHO cells deficient in Dihydrofolate reductase and treated with 5-aza-2'-deoxycytidine, the protein levels of GNAS and TRIM26 were significantly higher than those in normal control cells. These findings suggested that epigenetic status of genes in placenta have profound impacts on the development of NTDs.National Natural Science Foundation of China [31101013]; National Basic Research Program of China [2007CB511901, 2014CB138503]; State Key Laboratory for Molecular Developmental Biology [2013-MDB-ZD-04]SCI(E)PubMedARTICLExzheng@pku.edu.cn; rlma@genetics.ac.cn10605-6116