# Project 2: Epigenetic, Behavioral, and Physiological Outcomes in a Mouse ART Model > **NIH NIH P50** · UNIVERSITY OF PENNSYLVANIA · 2024 · $270,938 ## Abstract Abstract Assisted Reproductive Technologies (ART) are invaluable for the increasing number individuals who require interventions to treat their infertility. Nevertheless, ART-conceived children are at increased risk for loss-of- imprinting disorders, e.g., Angelman Syndrome, resulting from epigenetic errors, as well as placental disorders, abnormal growth, congenital malformations, and postnatal cardiac and metabolic disorders. These problems likely arise because ART procedures take place when the preimplantation embryo is being epigenetically reprogrammed. Because it is difficult to conduct studies using human embryos, a mouse model system, which anticipated risks associated with ART, will be used to assess the effect of ART interventions on placental morphology, imprinted gene regulation, growth, physiological phenotypes of the offspring, and epigenetic gene regulation, including DNA methylation and chromatin structure genome-wide. Oocyte vitrification is being increasingly used for donors as well as older women to prolong their fertility. Little is known, however, about its effects on embryo development and resulting offspring. Specific Aim 1 will use our mouse model to assess whether oocyte vitrification in the context of IVF exerts additional dysregulation of epigenetic profiles, placental morphology and fetal sufficiency. Moreover, although the majority offspring conceived using ART are healthy, a small percent have abnormal imprinted gene regulation and outlier DNA methylation phenotypes. Specific Aim 2 will characterize phenotypes associated with mice that have extremely abnormal DNA methylation at ICRs to determine if they too exhibit adverse metabolic and epigenetic outcomes as they age. Finally, very little work has addressed the mechanism(s) of adverse epigenetic patterns in ART conceptuses. Embryo culture disproportionately contributes to adverse phenotypes of IVF offspring, i.e., abnormal morphological and epigenetic patterns. We hypothesize that elevated oxygen concentration during embryo culture contributes to this phenotype via dysregulation of oxygen-sensitive proteins. Specific Aim 3 will examine the role of O2 environment in mediating adverse placental and embryonic outcomes in ART by adjusting oxygen concentration and assaying gestational outcomes. Additionally, to address the mechanism of elevated O2 in the extensive epigenetic dysregulation we observe in cultured embryos, we will focus on the histone demethylases, KDM6A (H3K27me2/3 demethylase) and KDM5A (H3K4me2/3 demethylase), whose enzymatic activity depends on O2 concentration, and determine changes in the global chromatin landscape of these two histone marks in blastocysts as a function of O2 concentration. Results of these experiments will provide information regarding the linkage between epigenetic changes and health of offspring conceived by ART. Together with results from other projects in this P50, our findings may identify experimental modifications to ART proced... ## Key facts - **NIH application ID:** 10992942 - **Project number:** 2P50HD068157-11A1 - **Recipient organization:** UNIVERSITY OF PENNSYLVANIA - **Principal Investigator:** MARISA S. BARTOLOMEI - **Activity code:** P50 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $270,938 - **Award type:** 2 - **Project period:** 2011-05-01 → 2028-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10992942 ## Citation > US National Institutes of Health, RePORTER application 10992942, Project 2: Epigenetic, Behavioral, and Physiological Outcomes in a Mouse ART Model (2P50HD068157-11A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10992942. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*