期刊
PLACENTA
卷 35, 期 12, 页码 981-988出版社
W B SAUNDERS CO LTD
DOI: 10.1016/j.placenta.2014.09.016
关键词
14-3-3 tau; Placenta; Preeclampsia; TETs; 5 hmC; Methylation
资金
- National Science Funds of China [81270712, 81100438, 81200449, 81200448]
- Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases
Introduction: Disruption of the 14-3-3 tau (YWHAQ) gene has been shown to be involved in preeclampsia (PE). The YWHAQ promoter could be differentially regulated by methylation in severe PE patients. Methods: Placental genomic DNA from patients with severe PE (n = 21) and controls who experienced a normal pregnancy (n = 16) was analyzed using dot-blot and immunohistochemistry. The placental methylation patterns of YWHAQ expression of 14-3-3 tau and ten-eleven translocation (TET), were confirmed by bisulfite sequencing, immunohistochemistry, western blot and real-time PCR, respectively. Results: Genomic 5 hmC (P < 0.001), expression of 14-3-3 tau (P < 0.01) and TET (P < 0.05) were downregulated, whereas 5 mC was up-regulated (P < 0.001) in preeclamptic placentas. Significant hypermethylation of the YWHAQ promoter was detected in PE placentas compared with control samples (19.1% vs. 9.4%, P = 0.0095). PE-specific hypermethylation of CpG2 - 4, CpG9, CpG17, CpG19 was identified in PE patients compared with controls (CpG2: 13.3% vs. 2.5%, P < 0.0001; CpG3: 14.8% vs. 3.1%, P < 0.0001; CpG4: 19.5% vs. 5.0%, P < 0.0001; CpG9: 15.7% vs. 5.0%, P = 0.0018; CpG17: 16.2% vs. 6.3%, P = 0.0003; and CpG19: 78.1% vs. 59.4%, P < 0.0001). Discussion: The observed participation of 14-3-3 tau in the regulation of the placental epigenome may participate in the molecular mechanisms that govern the pathological process of PE, although this requires further evaluation. (C) 2014 Elsevier Ltd. All rights reserved
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