Oxytocin shifts human myometrial cells from oxidative phosphorylation to glycolysis for energy during contraction.

The uterine myometrium requires substantial energy for sustained contractions during labor, crucial for fetal delivery and preventing postpartum hemorrhage. Current understanding of specific energy substrate preferences and metabolic flexibility in these cells, particularly under oxytocin stimulation, remains incomplete. This knowledge gap hinders the development of targeted interventions for conditions like uterine atony, where insufficient contractile force leads to excessive bleeding. Understanding how myometrial cells adapt their metabolism to meet high energy demands could reveal novel therapeutic targets.

Researchers investigated energy substrate preference and metabolic flexibility in quiescent and oxytocin-stimulated human myometrial cells. They assessed oxygen consumption rate (OCR) and metabolic shifts using mitochondrial oxidation inhibitors. Cells were treated with the glucose oxidation inhibitor UK5099, the long-chain fatty acid oxidation inhibitor etomoxir, and the glutamine oxidation inhibitor BPTES. The primary endpoints included changes in OCR and the impact on myometrial contractility, comparing responses in both quiescent and oxytocin-treated conditions to understand metabolic adaptation.

Human myometrial cells primarily rely on oxidative phosphorylation during quiescence, but demonstrate metabolic flexibility by shifting towards glycolysis when stimulated with oxytocin to meet higher energy demands. Basal oxygen consumption rate (OCR) significantly decreased upon treatment with the glucose oxidation inhibitor UK5099, but not with the long-chain fatty acid oxidation inhibitor etomoxir or the glutamine oxidation inhibitor BPTES. This indicates a strong dependence on glucose oxidation in quiescent cells. However, in oxytocin-treated myometrial cells, the OCR decrease was observed with BPTES treatment in addition to UK5099, suggesting that contractile myometrial cells can also utilize glutamine as an energy source.

Functionally, myometrial contractility was significantly reduced by UK5099, further confirming the critical role of glucose utilization in uterine muscle function. The lack of effect from etomoxir on contractility reinforces the minimal reliance on fatty acid oxidation for this process.