Gestational diabetes mellitus: intracellular pH and hydrogen sulfide as determinants of endothelial function and nitric oxide synthase regulation
Gestational diabetes mellitus: intracellular pH and hydrogen sulfide as determinants of endothelial function and nitric oxide synthase regulation
Gestational diabetes mellitus (GDM) is a pregnancy-related condition that impacts both maternal and fetal health. It is marked by elevated maternal blood sugar and increased insulin levels in the fetus. This thesis of Gonzalo Fuentes Rodríguez explores how GDM alters the function of the umbilical vein, particularly the endothelium—a layer of cells essential for nutrient and oxygen transport between mother and baby. In GDM, this layer becomes dysfunctional, impairing vascular tone and nutrient transport.
A central issue identified is the disruption of intracellular pH (pHi), driven by overactive sodium/proton exchangers (NHEs), which make the internal environment of endothelial cells too alkaline. The naturally produced gas molecule hydrogen sulfide (H₂S) was found to help correct this imbalance by inhibiting NHE activity, thereby lowering pHi and helping restore normal cell behavior. The thesis also considers how environmental exposures—such as vitamin and mineral deficiencies or pollutants like heavy metals—may worsen placental dysfunction in GDM.
Using human umbilical vein endothelial cells (HUVECs) from both normal and GDM pregnancies, the research demonstrates that maternal pre-pregnancy body mass index significantly affects pHi regulation and adenosine transport—both vital for vascular health. The study also reveals that H₂S modulates nitric oxide (NO) production through its effects on pHi, either promoting or suppressing NO synthesis depending on the cellular context.
Overall, the findings suggest that targeting pHi regulation and H₂S signaling could offer novel strategies for preventing or reducing vascular complications associated with GDM, while also underscoring the influence of maternal health and environmental exposures during pregnancy.