Embryopause · Decoding Stress and Chromatin Dynamics in Embryonic Dormancy: Unlocking resilience to improve implantation success

Embryo-endometrium asynchrony and implantation failure are major contributors of infertility, affecting over 15% of the EU population. Yet, how embryos sense and integrate maternal cues during the critical implantation window remains unclear. Over 130 mammalian species have evolved embryonic dormancy (diapause), a reversible developmental arrest at implantation triggered by maternal environment stressors such as nutrient deprivation. In this dormant state, embryos adapt to metabolic stress by reducing global RNA and protein synthesis, remodelling chromatin, arresting the cell cycle and maintaining the epiblast in a pluripotent, undifferentiated state. Dormancy integrates stress sensing, metabolic adaptation, and developmental coordination, offering a powerful model to study how embryos survive adverse maternal conditions. While diapause may not occur in humans, its molecular pathways are conserved, offering a comparative framework to investigate how stress influences cell fate decisions, preserves developmental potential, and coordinates survival processes essential for implantation success. This project will pioneer a mechanistic understanding of how pluripotency and chromatin architecture are maintained and reconfigured under stress while preserving embryo viability. I will address this critical gap by investigating three central questions: (1) What is the contribution of the Integrated Stress Response (ISR) to dormancy and survival? (2) How is the pluripotency network reconfigured under stress? and (3) What chromatin features are dynamically altered during dormancy? Using state-of-the-art genetic and pharmacological perturbations alongside cutting-edge proteomic, transcriptomic and epigenomic approaches in both mouse and stem cell-based dormancy models and supported by my host lab with expertise in early development and epigenetics, this work will uncover fundamental principles of embryogenesis and inform novel strategies to improve implantation outcomes.