br Materials and methods br Results br
Materials and methods
Discussion In our tissue array, we demonstrated that 14-3-3 tau mRNA and protein expression levels decreased in the preeclamptic placentas. 14-3-3 proteins are considered to be important in the functional regulation of trophoblasts and maybe associated with adverse pregnancy complications. Bin et al. indicated that 14-3-3 δ/ζ expression was up-regulated in the placental villi of gestational diabetes mellitus (GDM) compared with normal tissue . Park et al. reported an increase in 14-3-3 zeta expression in preeclamptic placentas compared with normal placentas . Another study showed that the 14-3-3 tau mRNA level was lower in preeclamptic placentas compared with controls , which was in agreement with our research. Additionally, animal experimentation has demonstrated that the 14-3-3 ε/ζ protein was clearly discriminating in the hypothalamus of in intrauterine growth retardation (IUGR) pups compared with the controls . Interestingly, 14-3-3 proteins have been found to exhibit anti-apoptotic characteristics . A decrease in the expression of 14-3-3 tau, as found in our research, could therefore increase apoptosis in placental MI-773 australia and subsequently cause an increase in the level of placental cellular debris shed into the maternal blood circulation. Furthermore, early detection of PE could be achieved by measuring placental DNA concentrations in maternal plasma, which has been indicated by several studies , . We theorize that in the present investigation, the reduced 14-3-3 tau gene expression in the PE placenta could be a result of hypermethylation of YWHAQ promoter. Although the methylation levels of these CpG sites were low, the cumulative effect of all CpG sites may impact the abnormal placental expression of 14-3-3 tau in PE patients. In general, methylation at CpG islands in a gene promoter favors transcriptional repression. Notably, the methylation status of the promoters of the 14-3-3 isoforms has been shown to influence their expression in various types of cancers , . In the multiple linear regression analysis, we identified a positive association between the methylation levels of the YWHAQ promoter and systolic/diastolic blood pressure in the PE group. Similarly, Kulkarni et al. revealed a positive correlation between global DNA methylation and systolic/diastolic blood pressure in a PE group . Altogether, this evidence supports a causal link between methylation modification of the YWHAQ promoters and the development of PE. The results of our study are encouraging; however, it must be noted that the small sample size limited the potential to detect between-group differences. Additionally, the global 5 mC was higher in the preeclamptic placentas compared with the normal placental tissues. An emerging concept within the field of placental epigenome is that epigenetic dysregulation occurs prior to conception or during pregnancy, and this dysregulation may increase the susceptibility to PE . Similarly, several studies have shown an increased global DNA methylation level in the PE group compared with the normotensive group , . However there were some other studies that show different results , . In the study of Nomura et al., global methylation of placenta tissue was analyzed using LUMA, and the difference was not statistically significant (57.43 vs. 54.02%, P = 0.05) . The Illumina HumanMethylation450 BeadChip was used to assess placental DNA methylation of early-onset preeclampsia (EOPE) in the research of Blair et al. . The effects of anti-hypertensive medicine on DNA methylation in the placenta are unstudied; however there are clear disruptions in the corticosteroid pathways in these samples , perhaps from the use of antenatal corticosteroids. In our study, bisulfite sequencing analysis was used to detect the 5 mC level. A mix of these factors, different participants criteria and different methods used driving the DNA methylation differences is plausible. Together, these studies imply that abnormal genomic methylation may contribute to the pathogenic process of PE.