Cervical function in pregnancy and disease: new insights from single-cell analysis

The uterine cervix plays an essential role in regulating fertility, maintaining pregnancy, remodeling in preparation for parturition, and protecting the reproductive tract from infection. A compromise in cervical function contributes to adverse clinical outcomes. Understanding molecular events that drive the multifunctional and temporally defined roles of the cervix is necessary to effectively treat infertility, reproductive tract infections, preterm birth, labor dystocia, and cervical cancer. The application of single-cell technologies to study cervical pathophysiology, while in its infancy, underscores the potential of these approaches in developing clinically relevant biomarkers of disease and preventative therapies. This review focuses on insights gained from single-cell transcriptomic studies in human and mouse cervical tissue and highlights outstanding questions in the field. One collective advance from single-cell analysis is the dynamic plasticity of cervical epithelial cells during the reproductive cycle in health and disease. Single-cell comparisons between upper and lower regions of the reproductive tract also highlight the distinct and divergent immunological responses elicited in the cervix during the reproductive lifespan. These findings may reconcile prior controversies in the role of proinflammatory mediators during parturition. In addition to providing obstetric insights, single-cell technologies elucidate the molecular pathways that drive cervical cancer progression. Thus far, these technologies have uncovered cellular heterogeneity in the tumor microenvironment and have identified potential cancer stem cells. While single-cell technology alone will not uncover all the molecular underpinnings contributing to preterm birth or cervical cancer, the insights derived from this valuable technology will accelerate our understanding of cervical biology in health and disease, which ultimately will help develop biomarkers for disease prediction and prevention therapies.