Gestational iron deficiency is a common occurrence during pregnancy, affecting nearly one in three women worldwide. It can lead to a host of adverse outcomes for both mother and baby, including impaired cognitive development, preterm birth, and low birth weight. Despite its prevalence, the cellular mechanisms underlying this condition remain poorly understood. Recent research has shed light on a potential cellular origin of gestational iron deficiency impairments, offering new insights into its pathogenesis and potential avenues for prevention and treatment.
Gestational iron deficiency (GID) is a condition that occurs when a pregnant woman does not have enough iron in her body to meet the demands of both herself and her growing fetus. This can lead to various impairments, including an increased risk of preterm delivery, low birth weight, and developmental delays in the baby. Despite numerous studies linking low iron levels in pregnant mothers to an increased risk of cognitive impairments, such as autism, attention deficit syndrome, and learning disabilities in their children, iron deficiency remains a widespread issue among pregnant women and young children.
The mechanisms by which GID contributes to cognitive impairment are not fully understood. However, researchers have identified a potential cellular source for the impairments related to GID. The laboratory of Margot Mayer-Proschel, Ph.D., a professor of Biomedical Genetics and Neuroscience at the University of Rochester Medical Center, was the first to demonstrate that the brains of animals born to iron-deficient mice react abnormally to excitatory brain stimuli, and that iron supplements given at birth does not restore functional impairment that appears later in life.
Most recently, her lab has made significant progress in the quest to find the cellular origin of the impairment and have identified a new embryonic neuronal progenitor cell target for GID. This study was recently published in the journal Development. By looking at the brains of adults and young mice born with known GID, Michael Rudy, Ph.D., and Garrick Salois, who were both graduate students in the lab and co-first authors of the study, found disruption of interneurons, cells that control the balance of excitation and inhibition and ensure that the mature brain can respond appropriately to incoming signals.
The researchers found that this specific progenitor cell pool was disrupted in embryonic brains exposed to GID. These findings provide evidence that GID affects the behavior of embryonic progenitor cells causing the creation of a suboptimal network of specialized neurons later in life. “Understanding that connection could lead to changes to healthcare recommendations and potential targets for future therapies,” said Mayer-Proschel.
Having identified cellular targets in a mouse model of GID, Neuroscience graduate student Salois in the Mayer-Proschel lab is now establishing a human model of iron deficiency using brain organoids—a mass of cells, in this case, that represent a brain. With these, researchers can mimic the development of the neuronal progenitor cells that are targeted by GID in the mouse.
“We believe this model will not only allow us to determine the relevance of our finding in the mouse model for the human system but will also enable us to find new cellular targets for GID that are not even present in mouse models,” said Mayer-Proschel. “Understanding such cellular targets of this prevalent nutritional deficiency will be imperative to take the steps necessary to make changes to how we think of maternal health. Iron is an important part of that, and the limited impact of iron supplementation after birth makes it necessary to identify alternative approaches.”
In conclusion, this groundbreaking research sheds light on the cellular processes involved in gestational iron deficiency impairments. Identifying the potential cellular origin of gestational iron deficiency impairments can pave the way for developing targeted therapies to mitigate the adverse effects experienced by pregnant women and their offspring. The findings of this study underscore the importance of prenatal care and the need to monitor hemoglobin levels during pregnancy rigorously. Now that we have a better understanding of the underlying mechanisms, researchers can work towards creating interventions that prevent long-term health consequences associated with gestational iron deficiency. We hope this research and the subsequent developments will positively impact the health outcomes of mothers and their babies in the coming years.
