An early-onset preeclampsia study of C19MC: DNA methylation in the spermatozoa and, DNA methylation and expression in the placental villi.

Abnormal paternal methylation of imprinted genes is associated with preeclampsia. C19MC is an imprinted miRNA cluster that plays an important role in placental development. Thus, the present study investigated methylation of C19MC in the spermatozoa and placentae and, its expression in the placentae of early-onset preeclampsia (EOPE). The study was carried out with n = 25 (controls) and 14 (EOPE cases). Methylation study of C19MC differentially methylated region (DMR) was performed by pyrosequencing of spermatozoa and placental villi samples. Expression levels of C19MC miRNAs in the placental villi were measured by small RNA sequencing on Illumina NovaSeq 6000. Publicly available datasets of EOPE were examined. The mRNA targets of differentially expressed miRNAs (DEMs) that were expressed in these datasets were subject to gene ontology analysis. The expression levels of target genes were quantified by qPCR. C19MC was not differentially methylated in the preeclampsia group spermatozoa. The DMR showed hypomethylation and, elevated expression of miR-518a-5p/527 and miR-520a-5p in the placental villi of the case group. The targets DAB2IP, ACAA2, TRAF2, VCAM1, CADM3, TWIST1 and CUL3 were significantly downregulated in the preeclamptic placentae. Birth weight and systolic blood pressure had a significant association with methylation in placental villi. The study is the first to explore methylation of C19MC in the spermatozoa and placentae from EOPE couples. Aberrant expression of C19MC miRNAs and their targets could be associated with pathophysiology of EOPE. The study paves the way for assessment of C19MC DEMs and target mRNAs as potential therapeutic targets for EOPE.