Tracy Bale, PhD

Professor of Pharmacology & Psychiatry
Director, Center for Epigenetic Research in Child Health and Brain Development
University of Maryland

Faculty Profile
Tracy Bale, PhD

Preconception delivery: Somatic signals impacting neurodevelopment and stress circuitry

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 preconception environment can be transmitted at fertilization and impact embryo development. In our models of male and female preconception stress we have been able to identify molecular mechanisms critical for parental transmission of stress signals. In males, 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. 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 reprogramming. 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. utilizing within and between human subject comparisons of sperm samples and neuropsychiatric perceived stress reports collected repeatedly over six months. In our female preconception stress model, we have found similar evidence for germ cell programming of offspring stress circuitry and body weight dysregulation. Together, these studies demonstrate in both mice and humans a clear involvement of stress in the environment to alter germ cell programming and a novel role for reproductive tract EVs to harness changes in the parental milieu and integrate into germ cell signals.

Tracy L. Bale, Ph.D. is a Professor of Pharmacology and Psychiatry, and Director of the Center for Epigenetic Research in Child Health and Brain Development in the School of Medicine. Dr. Bale completed her Ph.D. at the University of Washington and her postdoctoral work at the Salk Institute with Dr. Wylie Vale. She was previously a Professor of Neuroscience at the University of Pennsylvania for 15 years. Dr. Bale was recruited to the University of Maryland School of Medicine as a STRAP recruit and the Director of the Center for Epigenetic Research in Child Health and Brain Development. Dr. Bale’s research focuses on understanding the role of stress dysregulation in neurodevelopmental and neuropsychiatric diseases, and the sex differences that underlie disease vulnerability. Her groundbreaking work has uncovered the molecular mechanisms by which the environment influences parental germ cell signals and placental trophoblast development, altering fetal brain development and maturation. She has been the recipient of numerous awards for her research including the Richard E. Weitzman Memorial award from the Endocrine Society, the Medtronic Award from the Society for Women’s Health Research, the Daniel H. Efron award from the American College of Neuropsychopharmacology, the NIH Award from the International Federation of Placenta Associations, and the Joseph Erlanger Distinguished Lecturer Award from the American Physiological Society.

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