Growth of Oxygen Environment of the Newborn Vocal Fold Maculae Flavae as a Stem Cell Niche

Accumulating evidence indicates that the anterior and posterior maculae flavae of the human vocal fold mucosa function as niches for tissue stem cells. This study aimed to characterize the oxygen microenvironment of the maculae flavae in the newborn vocal fold and to clarify its potential involvement in metabolic regulation and the preservation of stem cell characteristics at birth.

Immunohistochemical analyses were performed on vocal fold specimens obtained from five normal human newborns at birth.

Cells located within the maculae flavae demonstrated immunoreactivity for hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), supporting the presence of a hypoxic microenvironment. These cells also expressed lactate dehydrogenase A (LDHA), a key enzyme in anaerobic glycolysis, and pyruvate dehydrogenase kinase 1 (PDK1), which inhibits mitochondrial pyruvate oxidation, indicating a metabolic preference for glycolysis over oxidative phosphorylation. In addition, cytoglobin, an oxygen-binding protein known to modulate intracellular oxygen homeostasis and suppress mitochondrial activity, was also expressed.

The findings indicate that the maculae flavae of the human newborn vocal fold are characterized by a hypoxic microenvironment in which resident cells predominantly depend on anaerobic glycolysis for energy production. This HIF-1α-mediated hypoxic condition may contribute to the maintenance of stem cell properties by limiting oxidative metabolism and reducing the accumulation of reactive oxygen species. Already at birth, such metabolic regulation is likely essential for preserving the undifferentiated state of stem cells and supporting the regenerative potential of the vocal fold mucosa.

NA.