Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption

The cervical epithelium undergoes continuous changes in proliferation, differentiation and function that is critical before pregnancy to ensure fertility and during pregnancy to provide a physical and immunoprotective barrier for pregnancy maintenance. Barrier disruption can lead to the ascension of pathogens that elicit inflammatory responses and preterm birth. Here we identify epithelial subtypes in the cervix of nonpregnant, pregnant and laboring mice using single cell- transcriptome and spatial analysis. We identify heterogeneous subpopulations of epithelia displaying spatial and temporal specificity in cell proliferation, turnover and transcriptional programs. Further we identify untimely proliferation and function of epithelial cells in a model of cervical epithelial barrier disruption. Together these data provide insights as to how the cervical epithelium undergoes a continuous remodeling to maintain a dynamically shifting state of homeostasis in pregnancy and labor and provide a framework by which to understand perturbations in epithelial cell health and host-microbe interactions that contribute to risk of premature birth. Single-cell sequencing of mouse cervices from six wild type timepoints: non-pregnant (diestrus (n=7) and estrus (n=2)), gestation day (GD) 6 (n=5), GD12 (n=4), GD15 (n=3), GD18 (n=3), and in-labor (n=3), and 2 HA KO timepoints: GD15 & GD18.