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EMBL - Sapienza Lecture
Postponed - Friday, 2 October 2020, 11:00Add to calendarEpigenetics of stress allostasis: somatic mechanisms for germ cell programming of offspring developmentTracy L. Bale, Center for Epigenetic Research in Child Health and Brain Development, University of Maryland School of Medicine, USAHost: Cornelius Gross / Andrea MeleSapienza Università di Roma - Aula Odeion - Museo dell'Arte Classica - P.le Aldo Moro, 5 - Roma, EMBL Rome
Abstract: Epigenetics of stress allostasis: somatic mechanisms for germ cell programming of offspring development

Tracy L. Bale, J. Chan, C. Morgan, N.A. Leu, S. Ament, B. Garcia, M. Kane, C.N. Epperson

Parental lifetime exposures to perturbations such as stress, infection, malnutrition, and advanced age have been linked with an increased risk for offspring disease, including a strong association with neurodevelopmental disorders. Our studies have focused on identifying the causal biological mechanisms whereby information in the environment can be transmitted in sperm. In these studies, we demonstrate a causal role for somatic-to-germline transmission of stress information capable of altering fetal neurodevelopment via extracellular vesicles (EVs) in a preclinical model, and we further establish the translational potential of this model in a human cohort. We identified broad histone and transcriptomic alterations in mouse epididymal epithelial cells (EECs) in vivo, with corresponding persistent changes in miRNA and proteomic extracellular vesicle cargo secreted from pure caput EEC populations in vitro. In these studies, the transmission of paternal stress and changes in epigenetic marks only occur following a stress recovery period suggesting a cellular allostatic shift in chromatin programming. Using a transgenic approach, we demonstrated in vivo that the EEC glucocorticoid receptor, a central node of cellular stress mechanisms, serves a key role in this cellular programming where genetic knockdown of this receptor rescued the germline transmission of the offspring stress phenotype. We further established the causal involvement of EEC EVs utilizing intracytoplasmic sperm injection of caput sperm incubated with EVs secreted following stress treatment recovery. Translationally, we have examined similar stress programming changes in human sperm miRNA content. We utilized within and between human subject comparisons of sperm samples and neuropsychiatric perceived stress reports collected repeatedly over six months to identify a distinct miRNA expression pattern from subjects showing a post-stress recovery state.
EMBL - Sapienza Lecture
Friday, 7 May 2021, 11:00Add to calendarTony Kouzarides , Gurdon Institute, Cambridge CB2 1QN, UK, United KingdomHost: Mathieu Boulard / Irene BozzoniCNR Seminar Room, EMBL Rome