Protein Arginine Methyl Transferase and Hemochorial Placentation

Successful mammalian reproduction depends on establishment of trophoblast cell lineage, which assures anchorage of the embryo to the mother, establishes a vascular connection to transport nutrients and gases and secretes hormones that are required for the progression of pregnancy. However, we have a poor understanding of epigenetic mechanisms that regulate the biology of trophoblast cells and placentation in post-implantation embryos. Our preliminary studies establish that protein arginine methyltransferases 1 (PRMT1), is conserved in trophoblast cells of developing mouse and human placentae. Our loss-of-function studies indicate a critical role of PRMT1 in placentation after embryo implantation. The overarching goal of this proposal is to elucidate how PRMT1 function regulates trophoblast development and placentation to establishment of pregnancy. Two specific aims are proposed. In Aim 1 we will using a conditional Prmt1 knockout mouse model we will test the hypothesis that, PTMT1 function in trophoblast cells optimizes placentation in post-implantation embryos.. In Aim 2, using human trophoblast stem cells and primary trophoblast cells of a developing mouse placenta, we will test the hypothesis that PRMT1 establishes a conserved gene expression program in mouse and human trophoblasts and PRMT1-mediated transcriptional program is a key molecular regulator of trophoblast cell biology during human placentation. Successful completion of this proposal will define PRMT1-regulated gene signatures in trophoblast cells that are critical for establishment of pregnancy after implantation. Defining these gene signatures will be an important step in identifying trophoblast-specific causes that lead to pathological pregnancies, such as early pregnancy loss. Project Number: 1R21HD119510-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Soumen Paul | Institution: UNIVERSITY OF KANSAS MEDICAL CENTER, KANSAS CITY, KS | Award Amount: $426,250 | Activity Code: R21 | Study Section: Pregnancy and Neonatology Study Section[PN] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R21HD11951001