Executive Summary : | Recurrent pregnancy loss (RPL) is a distressing condition affecting 1-2% of women globally and 7.46% in the Indian population. 50% of cases remain idiopathic, indicating a need to identify more factors contributing to the disease aetiology. Parental epigenetic factors, such as DNA methylation, ncRNAs, and histone modifications, play a critical role in embryo development, implantation, and placental development. In such cases, male factors may play a role in the disease etiology. Using Whole Genome Bisulfite Sequencing (WGBS), researchers explored genome-wide sperm methylation signatures in iRPL and their possible implications in 1st trimester recurrent pregnancy loss. They obtained differentially methylated CpGs within genes involved in embryo and placental development and a long list of differentially methylated non-coding RNA (lncRNA) genes. Alterations in methylation of spermatozoan lncRNA genes could persist during early gestation and hinder normal placental and embryonic development. Currently, no human studies on sperm lncRNA gene methylation and their implications in iRPL are available. The researchers aim to screen differentially methylated lncRNA genes involved in embryo and placenta development and those implicated in RPL pathology, validate these in a larger number of iRPL and fertile study populations, and evaluate their expression profiles in paired placental samples. In vitro studies will be conducted to understand the functional roles of selected lncRNA. |