title: Dynamic changes in the cervical epithelial tight junction complex and differentiation occur during cervical ripening and parturition.
abstract: Cervical epithelia have numerous functions that include proliferation, differentiation, maintenance of fluid balance, protection from environmental hazards, and paracellular transport of solutes via tight junctions (TJs). Epithelial functions must be tightly regulated during pregnancy and parturition as the cervix undergoes extensive growth and remodeling. This study evaluated TJ proteins, as well as markers of epithelial cell differentiation in normal and cervical ripening defective mice to gain insights into how the permeability barrier is regulated during pregnancy and parturition. Although numerous TJ proteins are expressed in the nonpregnant cervix, claudins 1 and 2 are temporally regulated in pregnancy. Claudin 1 mRNA expression is increased, whereas claudin 2 expression declines. The cellular localization of claudin 1 shifts at the end of pregnancy (gestation d 18.75) to the plasma membrane in a lattice pattern, consistent with TJs in the apical cells. The timing of claudin 1-enriched TJs coincides with initiation of terminal differentiation of cervical squamous epithelia as evidenced by the increased expression of genes by differentiated epithelia late on gestation d 18. The cervical ripening defective steroid 5alpha-reductase type 1 deficient mouse, which has an elevated local progesterone concentration, also has aberrant claudin 1 and 2 expressions, fails to form claudin 1-enriched TJs, and lacks normal expression of genes involved in epithelial terminal differentiation. These data suggest that changes in permeability barrier properties during cervical ripening are, in part, negatively regulated by progesterone, and that dynamic changes in barrier properties of the cervix occur during pregnancy and parturition.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032, USA.
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Timmons
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Mitchell
authors.forename: Christopher
authors.initials: C
authors.lastname: Gilpin
authors.forename: Mala S
authors.initials: MS
authors.lastname: Mahendroo
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D020070:Cervical Ripening / Q000378:metabolism / Q000502:physiology*; D002584:Cervix Uteri / Q000166:cytology* / Q000378:metabolism; D062445:Claudin-1; D062506:Claudin-4; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000235:genetics; D036801:Parturition / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D019108:Tight Junctions / Q000737:chemistry* / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein
chemical_list: D062445:Claudin-1; D062506:Claudin-4; C568113:Cldn1 protein, mouse; C568158:Cldn4 protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D010088:Oxidoreductases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C518406:Srd5a1 protein, mouse