Aging and estrogen effects on transcervical-transvaginal epithelial permeability

Abstract

The objective of the study was to understand age-related contributions of the resistance of the intercellular tight junctions (RTJ) and the resistance of the lateral intercellular space (RLIS) to the transcervical-transvaginal permeability. The experiments used normal human ectocervical epithelial cells obtained from women aged 36-65 yr. Twenty-four hours of treatment of cells with 10 nM 17β-estradiol decreased the R LIS, whereas longer treatments were required to decrease The R TJ. Aging had no effect on baseline or estrogen decrease in R TJ, but it blocked both baseline and the estrogen decrease in R LIS. Actin assays showed age-related decrease in the fraction of monomeric G-actin and attenuation of sodium-nitroprusside-induced increase in G-actin. These results suggest that the aging-related diminished capacity of human ectocervical epithelial cells to remodel cellular actin from polymerized actin toward monomeric G-actin confers increased cell rigidity and therefore increased RLIS. Therefore, the hypoestrogenism-related decrease in RTJ and the hypoestrogenism- and aging-related increase in R LIS could be the cellular mechanisms of decreased permeability that lead to decreased fluid transport and decreased lubrication of the lower genital tract in older postmenopausal women.