Grant Project Title:
Identification of transcriptomic and epigenetic coordinates for post-implantation human embryonic development
Post-implantation human embryonic development beyond the blastocyst stage is pertinent to a variety of disorders in human reproduction such as implantation failure, fetal defects, placental insufficiencies and early pregnancy loss. However, our knowledge of cell-lineage decisions in the post-implantation human embryo remains severely limited and there is a critical need to explore the molecular control underlying the formation of trophoblast, epiblast and hypoblast lineages and the events surrounding implantation and gastrulation. In addition, it remains one of the premier goals of reproductive medicine to identify effective biomarkers that predict successful post-implantation development and pregnancy following uterine transfer of in-vitro fertilization (IVF) embryos. Our long-term goal is to understand cellular differentiation in the post-implantation human embryo at the molecular level and develop novel genomic predictors of pregnancy outcomes for pre-implantation testing of IVF embryos. This project aims to delineate the transcriptomic and epigenomic changes underlying human post-implantation lineage development and use this dataset to develop transcriptional and epigenetic predictors of successful implantation and gastrulation using a human post-implantation model in vitro.
We are immensely grateful to the ASRM Research Institute for supporting this project. It is very difficult to obtain funding for this line of research because the NIH currently restricts research projects involving reproductive medicine. As such, the ASRM Research Institute plays an important and unique role in funding basic research in human embryology and this support will unlock the tremendous translational potential in this field going forward. In our case it allows us to use cutting edge single cell multiome sequencing technology to address a fundamental question in reproductive biology – what are the molecular building blocks of a successful post-implantation human embryo and how can these single cell genomic technologies be used to identify high implantation potential embryos prior to uterine transfer?
Werner Neuhausser, MD PhD
Instructor in Obstetrics, Gynecology and Reproductive Biology
Division of Reproductive Endocrinology & Infertility
Beth Israel Deaconess Medical Center
Harvard Medical School