Functional and Molecular Characterization of Epithelial Subtypes in Cervical Remodeling and Preterm Birth

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Abstract Preterm birth due to an ascending infection accounts for 25-40% of spontaneous preterm births. Disruptions in the cervical epithelia that perturb its barrier and immune function is a risk factor for an ascending infection. Using single cell transcriptomic and spatial approaches, epithelia subpopulations were identified in cervices from nonpregnant mice and mice at gestation days 6, 12, 15, 18 and in labor. Unique to pregnancy was the expansion of two populations of secretory goblet cells which produce a distinct mucus network and immune surveillance factors. In the current proposal, we aim to identify the lineage of these secretory cells which express markers of both squamous and columnar epithelia, and to define the progesterone and estrogen dependent gene regulatory networks that regulate proliferation and differentiation of the two goblet subtypes. Using single cell datasets from mice with epithelial barrier defects or mice with exposure to lipopolysaccharide to induce inflammation, we will define perturbations in epithelial subtype functions that contribute to ascending infection risk. Finally, the expression of olfactomedin 4, one immune surveillance factor upregulated in the goblet cells in pregnancy, will be measured in cervico-vaginal fluid from women in each trimester of a term or preterm pregnancy to determine its utility to monitor cervical epithelial cell health and risk of spontaneous preterm births.