Research Projects

Recurrent pregnancy loss (RPL), defined as two or more consecutive loss of clinical pregnancy before 20 weeks of gestation. Studies have proposed certain risk factors such as, hormonal and metabolic disorders, uterine anomalies, cytogenetic abnormalities and various immunological and genetic factors, responsible for RPL. Genetic alterations which are responsible for RPL, can be present in either of the 3 genomes: mother, father and their fetuses. In addition, environmental factors interacting with these three genomes can affect germline cells. In this context, we have done extensive research to investigate the genetics of RPL through Next Generation Sequencing (NGS; couple exome and TRIO exomes) in combination with cytogenetic tests (Karyotyping and chromosomal microarray) which helped us in understanding the underlying etiology of RPL. Our preliminary findings under CRG/2020/002787 project indicated mutations in few important genes which are involved in vital pathways, placental development, immunomodulation, early embryonic development and fetal demise. Despite the multiple causes listed above, there remains a significant challenge in determining the cause in approximately 40–60% of patients with RPL, commonly referred to as recurrent unexplained pregnancy loss (URPL). Therefore, the pathogenesis of RPL remains to be elucidated. The placenta and maternal decidua undergo remarkable transformations in order to establish and sustain pregnancy. They work dynamically in a highly regulated manner to detect pregnancy; provide bodily support and immune tolerance; facilitate maternal-fetal transfer of nutrients, waste products and gas exchange; and produce hormones and other physiologically active factors. Abnormalities in the early stages of placental development can manifest as RPL and pregnancy-related complications. This provides a rationale only for studying pregnancy, analyzing various cell types, cell subpopulations, and factors such as variability in gene expression at the level of individual cells in the feto-maternal interface will help in the understanding of intercellular and intracellular mechanisms and interactive dialogue to facilitate cell differentiation to better understand cell development and fate at the maternal-fetal interface. The diversity of cell types, lineage and differentiation stage-specific molecular properties, and functional interactions between cell types are well studied. Two recent studies using scRNA-seq have identified a subset of CD39+ dNK cells supporting embryonic growth that is proportionally reduced in RPL patients. However, the global immune variations at the maternal-fetal interface of RPL remains elusive. In this study, scRNA-seq will be leveraged to unravel the cell heterogeneity of maternal decidua and chorionic villi in normal and URPL groups in the first trimester, along with comprehensive profiling of the decidual CD45+ immune cells to understand the immune microenvironment at feto-maternal interface.