Molecular characterization of human pregnancy-induced cervical epithelium

The cervical epithelium serves as the first line of defense to limit ascending infections into the upper reproductive tract. Previous animal studies have demonstrated the functional role of cervical epithelial cells in protecting against ascending infection-mediated PTB. However, there remains a gap in our understanding of the molecular mechanisms regulating cervical epithelial cell barrier function in human pregnancy due to ethical constraints and a lack of proper tools. To fill the knowledge gap, organoid models from nonpregnant human cervix have been established. However, there are currently no organoid models of human cervix that recapitulate the dynamic molecular states of epithelial cells during pregnancy. We reason that the primary obstacle that prevents the establishment of such a human in vitro cervix model is a scarcity of in vivo molecular information on the human cervical epithelium before and during pregnancy. To this end, we aim to build novel in vitro human cervical organoid-stromal cell co-culture models relevant to pregnancy and nonpregnancy through a two-pronged approach. First, we will apply single cell and spatial transcriptomics technologies to cervical tissue samples from nonpregnant and term pregnant women to molecularly characterize the human endocervix and ectocervix and to delineate the cervical epithelium-stroma interactions before and during pregnancy (Aim 1). Second, we will develop a co-culture model of human cervix epithelia and fibroblasts to better model the cervical epithelium-stroma interactions before and during pregnancy (Aim 2). The overall impact of this work is to lay a solid foundation for the identification of molecular mechanisms required for epithelial barrier function which is necessary to identify potential disruptors of epithelial barrier function that predispose women to ascending infection mediated preterm birth. Project Number: 1R21HD118291-01A1 | Fiscal Year: 2026 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: MALA MAHENDROO (+1 co-PI) | Institution: UT SOUTHWESTERN MEDICAL CENTER, DALLAS, TX | Award Amount: $456,500 | Activity Code: R21 | Study Section: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER] View on NIH RePORTER: https://reporter.nih.gov/project-details/11303783