Protein arginine methyl transferase and hemochorial placentation

The University of Kansas Medical Center Research Institute, Inc. received a $426,250 Project Grant award dated August 6, 2025, from the National Institute of Child Health and Human Development (NICHD) under the Child Health and Human Development Extramural Research program (CFDA 93.865). The award supports research through July 31, 2027, investigating the role of Protein Arginine Methyltransferase 1 (PRMT1) in regulating trophoblast development and placentation during pregnancy establishment.

The research deliverables include identification of PRMT1-regulated gene signatures critical for trophoblast cell biology through two primary aims: (1) using conditional PRMT1 knockout mouse models to elucidate the enzyme's function in optimizing placentation post-implantation, and (2) employing human trophoblast stem cells and primary mouse trophoblast cells to identify conserved gene expression programs mediated by PRMT1 across species. The project's ultimate objective is to define molecular mechanisms underlying trophoblast-specific dysfunction that may lead to pathological pregnancy outcomes such as early pregnancy loss, thereby advancing understanding of epigenetic regulation in human reproduction and development.

Abstract

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.