Placental function in brain development and damage

Our laboratory’s goal is to understand the hormonal factors that contribute to normal neurodevelopment and the impact of their loss following premature birth or placental compromise so that we can develop novel neuroprotective replacement therapies.

Many events including infection, malnutrition, and genetic abnormalities can disrupt the placenta’s function, or - as in preterm birth - can abruptly change the brain’s hormonal environment. Such changes may directly damage the developing brain or increase its susceptibility to the damage that leads to cerebral palsy or developmental delay. The laboratory has taken a multi-faceted approach to understanding these hormonal mechanisms and developing systems in which we can test potential interventions:

  • Supported by a 2009 National Institutes of Health Director’s New Innovator Award, our laboratory has developed genetic models to directly assess the impact of specific placental hormones on fetal brain development. The experiments demonstrate that the loss of a specific steroid from the placenta, allopregnanolone, changes cortical neural progenitor proliferation. This work has opened up the possibility of early replacement of this hormone, and others like it, to help normalize brain development. 
  • Our laboratory, led by Dr. Penn and her team, has initiated experiments to investigate sex differences in a chronic sub-lethal hypoxia mouse model that closely mimics the brain damage seen after preterm birth. This work has resulted in a series of papers in Pediatric Research on the short- and long-term sex-linked effects of hormones and hypoxia.
  • To facilitate the translation of this research, Dr. Penn collaborated with computer science colleagues at Stanford University to develop new and rapid ways to predict which preterm infants are most likely to suffer brain damage, and might benefit most from hormonal or other interventions. Their work on this method, dubbed ‘PhysiScore’ and published in Science Translational Medicine, received significant national and international press.
  • The pilot study on the correlation between neonatal Cerebrospinal Fluid (CSF) oxytocin levels and later behavioral outcomes was published in Psychoneuroendocrinology. At Children’s National the lab is taking this data back into the laboratory, working with models that display changes in placental oxytocin levels to investigate potential mechanisms of such long-term differences.

Dr. Penn's research interests include: