Transcription factors as essential regulators of myometrial smooth muscle cell function during pregnancy and labor

Parturition is a tightly regulated process coordinated by myometrial smooth muscle cells, which generate the uterine contraction required for birth. Preterm labor, defined as labor occurring before 37 weeks of gestation, remains a significant clinical challenge due to its association with adverse short and long-term risks on neonatal and maternal health. Earlier and recent studies provide strong evidence that transcription factors are performing crucial functions in uterine smooth muscle cells. In this review, we focus on the PR/ER, PPAR, NF-κB, AP-1, NFE2L2, and MAFF transcription factors and provide a comprehensive overview of their respective roles in myometrial smooth muscle cell function and the labor process. We also briefly discuss other transcriptional regulators that have been linked to uterine quiescence during pregnancy, to activation of the labor process or to both functions. Collectively, these transcription factors control various cellular processes, including inflammation, regulation of cytokine, chemokine and metalloproteinase expression, oxidative stress response, prostaglandin synthesis, calcium signaling, and contractility. Monitoring and targeting these transcription factors and associated pathways in the uterus are key for delaying or preventing preterm labor through the design of novel diagnostic and therapeutic tools to improve birth outcomes.