From Neurodevelopmental Models to Endocrine Disruption: Metabolomic Insights from In Vitro and In Vivo Studies
Chemist Sara Evangelista focused on how endocrine disrupting chemicals (EDCs) can affect early brain development and contribute to long-term cognitive and behavioral problems. Early life is a vulnerable period in which hormones, neurotransmitters, and lipids govern key neurodevelopmental processes, making these systems potential targets for chemical disruption.
To better understand the underlying mechanisms, Evangelista combined rat studies with human cortical brain organoids (CBOs), an emerging model that mimics early human brain development. The CBO research provided a metabolic and lipidomic reference framework for evaluating the extent to which this model reflects the neurodevelopmental pathways relevant to toxicity testing. Parallel to this, she investigated how perinatal exposure to selected EDCs alters metabolic and hormonal pathways in the developing rat hippocampus and whether these early changes are associated with later behavioral deficits. The overarching motivation was to generate mechanistic insights that would support more predictive and human-relevant approaches to assessing developmental neurotoxicity.
Normal Brain Development Can Be Disrupted
The research demonstrated that certain chemicals we are exposed to daily—known as endocrine disruptors (EDCs)—can disrupt normal brain development when exposure occurs very early in life. In rats, Evangelista found that these chemicals altered key molecules in the developing brain, such as hormones, lipids, and neurotransmitters, all of which are necessary for healthy growth. Some of these early changes were associated with learning and memory problems later in life, demonstrating that early disruption can have lasting consequences.
Promising Laboratory Models
Human stem cell-derived brain organoids ("mini-brains") have also been shown to develop metabolic characteristics similar to those observed in early human brain development. This means they can serve as promising laboratory models for studying how chemicals can affect the developing brain without relying solely on animal testing. Overall, my work provides early warning signs and tools to better identify chemicals that can harm brain development.
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