Methylation Status at DMRs of C14MC and C19MC in Spermatozoa and Chorionic Villi of Individuals Experiencing Recurrent Spontaneous Abortions.

Abstract

Recurrent spontaneous abortions (RSA) is defined as a loss of two or more consecutive clinically recognized pregnancies before the 20th week of gestation. In RSA, several causative maternal factors are known, but still, 50% of the cases remain unexplained. Evidence suggests that paternal factors are also equally important. Epigenetic phenomenon such as genomic imprinting and regulation of gene expression by miRNAs plays an important role in embryonic and placental development. Two large miRNA clusters, C14MC (Chromosome 14 microRNA cluster) and C19MC (Chromosome 19 microRNA cluster) are imprinted and expressed in the placenta during pregnancy and are known to regulate functionally important processes such as the trophoblast proliferation, adhesion, and migration. Hence, we studied the DNA methylation at the Differentially Methylated Regions (DMRs) of these clusters in spermatozoa and chorionic villi by pyrosequencing. In Spermatozoa, few Cytosine followed by Guanosine (CpG) sites at DMRs of C14MC and C19MC showed significant hypermethylation. In Chorionic villi, CpG sites showed significant hypomethylation in the RSA group as compared to control group. Semen parameters like sperm concentration, sperm motility, morphology, and chromatin compaction were comparable in control and RSA groups. The study suggests aberrant DNA methylation in spermatozoa and chorionic villi at DMRs of both miRNA coding clusters to be associated with RSA.