Hyperosmolal vaginal lubricants markedly reduce epithelial barrier properties in a three-dimensional vaginal epithelium model

Abstract

Most of the widely used vaginal lubricants in the U.S. and Europe are strongly hyperosmolal, formulated with high concentrations of glycerol, propylene glycol, polyquaternary compounds or other ingredients that make these lubricants 4 to 30 times the osmolality of healthy vaginal fluid. Hyperosmolal formulations have been shown to cause marked toxicity to human colorectal epithelia in vivo, and significantly increase vaginal transmission of genital herpes infections in the mouse/HSV model. They also cause toxicity to explants of vaginal epithelia, to cultured vaginal epithelial cells, and increase susceptibility to HIV in target cells in cell cultures. Here, we report that the osmolality of healthy vaginal fluid is 370 ± 40 mOsm/Kg in women with Nugent scores 0-3, and that a well-characterized three-dimensional human vaginal epithelium tissue model demonstrated that vaginal lubricants with osmolality greater than 4 times that of vaginal fluid (>1500 mOsm/Kg) markedly reduce epithelial barrier properties and showed damage in tissue structure. Four out of four such lubricants caused disruption in the parabasal and basal layers of cells as observed by histological analysis and reduced barrier integrity as measured by trans-epithelial electrical resistance (TEER). No epithelial damage to these layers was observed for hypo- and iso-osmolal lubricants with osmolality of <400 mOsm/Kg. The results confirm extensive reports of safety concerns of hyperosmolal lubricants and suggest the usefulness of reconstructed in vitro vaginal tissue models for assessing safety of lubricants in the absence of direct clinical tests in humans.

Keywords: EpiVaginal tissue; Epithelial damage; Osmolality; Vaginal lubricant.

Fig. 1

Osmolality of unmodified vaginal secretions collected at random times during the menstrual cycles of women.

Fig. 2

Shows a trend line of a decrease barrier integrity (quantified by TEER measurement) and compromised tissue morphology (histology scores) as a function of an increase in osmolality of vaginal lubricants. Dark dots indicate% TEER measurement and Open circles indicate histological scores.

Fig. 3

A–L: H&E stained histological cross-sections of in vitro reconstructed Epivaginal epithelial tissue model treated with over the counter vaginal lubricants for 24 h. Water treated tissues were used as controls. Histology sections are arranged in order of increasing osmolality of the controls, and the lubricants.