Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption

Anne Cooley; ShanmugaPriyaa Madhukaran; Elizabeth Stroebele; Mariano Colon Caraballo; Lei Wang; Yucel Akgul; Gary C Hon; Mala Mahendroo

doi:10.1016/j.isci.2023.105953

Dynamic states of cervical epithelia during pregnancy and epithelial barrier disruption

iScience. 2023 Jan 12;26(2):105953. doi: 10.1016/j.isci.2023.105953. eCollection 2023 Feb 17.

Authors

Anne Cooley¹, ShanmugaPriyaa Madhukaran², Elizabeth Stroebele¹, Mariano Colon Caraballo², Lei Wang¹, Yucel Akgul³, Gary C Hon^{1

2

4}, Mala Mahendroo^{1

2}

Affiliations

¹ Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
² Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
³ Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁴ Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract

The cervical epithelium undergoes changes in proliferation, differentiation, and function that are critical to ensure fertility and maintain pregnancy. Here, we identify cervical epithelial subtypes in non-pregnant, pregnant, and in labor mice using single-cell transcriptome and spatial analysis. We identify heterogeneous subpopulations of epithelia displaying spatial and temporal specificity. Notably in pregnancy, two goblet cell subtypes are present in the most luminal layers with one goblet population expanding earlier in pregnancy than the other goblet population. The goblet populations express novel protective factors and distinct mucosal networks. Single-cell analysis in a model of cervical epithelial barrier disruption indicates untimely basal cell proliferation precedes the expansion of goblet cells with diminished mucosal integrity. These data demonstrate how the cervical epithelium undergoes continuous remodeling to maintain dynamic states of homeostasis in pregnancy and labor, and provide a framework to understand perturbations in epithelial health that increase the risk of premature birth.

Keywords: Biological sciences; Genetics; Genomics; Pregnancy.

Abstract

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