Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Cells. 2023 Apr 11;12(8):1130. doi: 10.3390/cells12081130.
Intrauterine growth restriction (IUGR) and preeclampsia (PE) are placental pathologies known to complicate pregnancy and cause neonatal disorders. To date, there is a limited number of studies on the genetic similarity of these conditions. DNA methylation is a heritable epigenetic process that can regulate placental development. Our objective was to identify methylation patterns in placental DNA from normal, PE and IUGR-affected pregnancies. DNA was extracted, and bisulfite was converted, prior to being hybridized for the methylation array. Methylation data were SWAN normalized and differently methylated regions were identified using applications within the USEQ program. UCSC's Genome browser and Stanford's GREAT analysis were used to identify gene promoters. The commonality among affected genes was confirmed by Western blot. We observed nine significantly hypomethylated regions, two being significantly hypomethylated for both PE and IGUR. Western blot confirmed differential protein expression of commonly regulated genes. We conclude that despite the uniqueness of methylation profiles for PE and IUGR, the similarity of some methylation alterations in pathologies could explain the clinical similarities observed with these obstetric complications. These results also provide insight into the genetic similarity between PE and IUGR and suggest possible gene candidates plausibly involved in the onset of both conditions.
胎儿宫内生长受限 (IUGR) 和子痫前期 (PE) 是已知会使妊娠复杂化并导致新生儿疾病的胎盘病变。迄今为止，关于这些病症遗传相似性的研究数量有限。DNA 甲基化是一种可遗传的表观遗传过程，可调节胎盘发育。我们的目标是确定正常、PE 和 IUGR 受影响妊娠的胎盘 DNA 中的甲基化模式。提取 DNA，然后进行亚硫酸氢盐转化，然后进行甲基化阵列杂交。使用 SWAN 对甲基化数据进行标准化，并使用 USEQ 程序中的应用程序识别差异甲基化区域。UCSC 的基因组浏览器和斯坦福大学的 GREAT 分析用于识别基因启动子。通过 Western blot 确认受影响基因的共性。我们观察到 9 个明显低甲基化区域，其中 2 个在 PE 和 IGUR 中均明显低甲基化。Western blot 证实了共同调节基因的差异蛋白表达。我们得出结论，尽管 PE 和 IUGR 的甲基化谱具有独特性，但这些病理中的一些甲基化改变的相似性可以解释与这些产科并发症相关的临床相似性。这些结果还提供了关于 PE 和 IUGR 之间遗传相似性的见解，并提出了可能涉及两种情况发生的潜在基因候选者。
