Differential gene expression and limited epigenetic dysregulation at the materno-fetal interface in preeclampsia

Abstract

Despite the many advances made in the diagnosis and management of preeclampsia, this syndrome remains a leading cause of maternal mortality and life-long morbidity, as well as adverse fetal outcomes. Successful prediction and therapeutic intervention require an improved understanding of the molecular mechanisms, which underlie preeclampsia pathophysiology. We have used an integrated approach to discover placental genetic and epigenetic markers of preeclampsia and validated our findings in an independent cohort of women. We observed the microRNA, MIR138, to be upregulated in singleton preeclamptic placentas; however, this appears to be a female infant sex-specific effect. We did not identify any significant differentially methylated positions (DMPs) in singleton pregnancies, indicating that DNA methylation changes in mild forms of the disease are likely limited. However, we identified infant sex-specific preeclampsia-associated differentially methylated regions among singletons. Disease-associated DMPs were more obvious in a limited sampling of twin pregnancies. Interestingly, 2 out of the 10 most significant changes in methylation over larger regions overlap between singletons and twins and correspond to NAPRT1 and ZNF417.

Hemostasis in Pre-Eclamptic Women and Their Offspring: Current Knowledge and Hemostasis Assessment with Viscoelastic Tests

“…The familial form of PE is associated with a more severe phenotype [25][26][27]. Genes implicated in endothelial function, lipid metabolism, oxidative stress, immune response, and thrombophilia have been associated with PE [27][28][29][30][31][32][33]. Environmental factors affect the phenotypic expression; thus, it will vary among similar genotypes [34].…”

Significance of Sex Differences in ncRNAs Expression and Function in Pregnancy and Related Complications

“…MicroRNAs are single-stranded ncRNAs (~21-24 nt) that regulate gene expression at the post-transcriptional level by silencing specific target RNAs or by targeting regulatory RNAs such as lncRNAs [22]. Each miRNA can target hundreds or thousands of mRNAs, and their deregulation is associated with an increasing number of human diseases [24][25][26], including several pregnancy-associated disorders [14,27] namely, spontaneous preterm birth [28], small-for-gestational-age (SGA) births [29], ectopic pregnancy [30], GDM [31], and PE [32]. PIWI-interacting RNAs (piRNAs) are another class of short ncRNAs (26-31 nt) involved in the differentiation of embryonic stem cells and in early embryonic development.…”

“…Li H and colleagues did not find any difference in exosomal miRNA expression between female or male fetuses in plasma of women with PE [ 100 ], whereas Leseva’s group observed mir-138 upregulation in placentas of mothers carrying female fetuses. Mir-138 regulates many cellular processes, including cell migration, epithelial-to-mesenchymal transition, cell cycle progression, and cell differentiation, which are connected to placental adaption [ 32 ].…”