MaterMeta · Elucidating the role of maternal nutrient stores in the metabolism of the preimplantation embryo

The first cell divisions of an embryo occur in the absence of transcription. Therefore, early embryonic development is dependent on maternally stored proteins and mRNA. Recent findings have shown that maternally deposited proteins are long-lived, suggesting that they play critical roles beyond fertilization. Interestingly some of these long-lived proteins play a role in metabolism. Maternal nutrient stores such as lipids and glycogen are available in the oocyte, however to what degree and when they contribute to the metabolism and epigenetic state of the embryo is poorly defined. In metabolic disorders linked to infertility such as obesity, diabetes and polycystic ovarian syndrome (PCOS) these maternal stores are changed. This project aims to investigate how maternal glycogen and lipid stores regulate the metabolic reprogramming of preimplantation embryos and characterize the metabolic awakening of the embryo. First, I will use 13C isotope-labeled nutrients and MALDI-MSI to trace when maternal stores are utilized in preimplantation mouse embryos. Second, I will perturb glycogen and lipid stores using dietary, mRNA or protein depletion (siRNA/TRIM-Away), and pharmacological tools to determine their functional role in development. Overall, this study will provide the first spatio-temporal map of maternal nutrient utilization in early embryos and functionally define the role of metabolic stores. The insights gained will improve our understanding of metabolic regulation during early development and may inform future strategies for enhancing IVF outcomes and reproductive health.