Effects of menopause and estrogen on cervical epithelial permeability

The objective of the study was to characterize the effect and explore the m echanisms by which menopause affects paracellular permeability of cultured human cervical epithelium. The experimental system was cultures of human ec tocervical epithelial (hECE) cells on filters. Assays included flux measure ments of cell-impermeable molecules and determinations of transepithelial e lectrical conductance. hECE cells of postmenopausal women formed epithelia with lower paracellular permeability than hECE cells of premenopausal women . Treatment with estrogen increased paracellular permeability, but levels r emained lower compared to cultures from premenopausal women. Lowering extra cellular calcium or treatment with cytochalasin-D, conditions that decrease the tight junctional resistance (R-TJ), increased the permeability and the relative effects were greater in cells of premenopausal women than in post menopausal women. Treatment of cells with sn-1,2-dioctanoyl diglyceride, an agent that increases the R-TJ decreased the permeability, and the relative effect was greater in cells of postmenopausal women than in cells of preme nopausal women. Estrogen had no significant effect on the responses to low calcium, cytochalasin-D, or sn-1,2-dioctanoyl diglyceride. Hydrostatic and hypertonic gradients in the subluminal to luminal direction, conditions tha t decrease the resistance of the lateral intercellular space increased the permeability to a similar degree in cultures of cells from premenopausal an d from postmenopausal women. Pretreatment with estrogen augmented the incre ases in permeability in response to hydrostatic and hypertonic gradients. I n cells exposed to low extracellular calcium, hydrostatic gradients had an additive increase in permeability. By extrapolation it was determined that in cultures of postmenopausal women R-TJ contributes 97% to the total parac ellular resistance, whereas in hECE cultures of premenopausal women the R-T J contributes only 84%. These results indicate that after menopause the tra nscervical paracellular permeability decreases significantly; this can expl ain the decrease in lubrication of the cervix and vagina in postmenopausal women. Part of the effect is due to lack of estrogen, and it can be reverse d by treatment with the hormone. However, most of the effect is unrelated t o estrogen and is caused by an increase in R-TJ.