Effects of reproductive hormones on experimental vaginal candidiasis - PubMed (original) (raw)
Effects of reproductive hormones on experimental vaginal candidiasis
P L Fidel Jr et al. Infect Immun. 2000 Feb.
Abstract
Vulvovaginal candidiasis (VVC) is an opportunistic mucosal infection caused by Candida albicans that affects large numbers of otherwise healthy women of childbearing age. Acute episodes of VVC often occur during pregnancy and during the luteal phase of the menstrual cycle, when levels of progesterone and estrogen are elevated. Although estrogen-dependent experimental rodent models of C. albicans vaginal infection are used for many applications, the role of reproductive hormones and/or their limits in the acquisition of vaginal candidiasis remain unclear. This study examined the effects of estrogen and progesterone on several aspects of an experimental infection together with relative cell-mediated immune responses. Results showed that while decreasing estrogen concentrations eventually influenced infection-induced vaginal titers of C. albicans and rates of infection in inoculated animals, the experimental infection could not be achieved in mice treated with various concentrations of progesterone alone. Furthermore, progesterone had no effect on (i) the induction and persistence of the infection in the presence of estrogen, (ii) delayed-type hypersensitivity in primary-infected mice, or (iii) the partial protection from a secondary vaginal infection under pseudoestrus conditions. Other results with estrogen showed that a persistent infection could be established with a wide range of C. albicans inocula under supraphysiologic and near-physiologic (at estrus) concentrations of estrogen and that vaginal fungus titers or rates of infection were similar if pseudoestrus was initiated several days before or after inoculation. However, the pseudoestrus state had to be maintained for the infection to persist. Finally, estrogen was found to reduce the ability of vaginal epithelial cells to inhibit the growth of C. albicans. These results suggest that estrogen, but not progesterone, is an important factor in hormone-associated susceptibility to C. albicans vaginitis.
Figures
FIG. 1
Effect of estrogen concentration on the induction and maintenance of experimental vaginal C. albicans infection. Animals were treated subcutaneously with various concentrations of estradiol valerate or sesame seed oil alone (none) 72 h prior to vaginal inoculation and weekly thereafter until completion of the study. At days 7, 14, and 35 postinoculation, groups of five to six randomly selected animals per group were sacrificed, and vaginal fungal burden was determined by quantitative vaginal lavage culture. CFU ± standard errors of the means (SEM) from five separate experiments are shown.
FIG. 2
Effects of progesterone on experimental C. albicans vaginal infections. Animals were treated with estrogen (Est; 0.2 mg/mouse) and/or progesterone (Pro; 1.0 mg/mouse) or sesame seed oil alone (none) subcutaneously 72 h prior to vaginal inoculation and weekly thereafter until completion of the study. At days 6, 13, and 20 postinoculation, five to six randomly selected animals per group were footpad challenged with CaCF, and DTH was measured 24 h later. Thereafter, mice were sacrificed and vaginal fungal burden was determined by quantitative vaginal lavage culture. (A) CFU ± standard errors of the means (SEM) from two experiments. (B) DTH (difference in thickness of footpad given Candida antigen versus footpad given PBS) ± SEM from estrogen-treated, progesterone-treated, or estrogen-plus-progesterone-treated mice.
FIG. 3
Effect of progesterone (Pro) on secondary (Sec) vaginal C. albicans infections. Animals were vaginally inoculated in the absence of estrogen. Four weeks later the mice received the first of weekly injections of estrogen (Est; 0.02 mg/mouse) or estrogen plus progesterone (1.0 mg/mouse), and they were inoculated intravaginally a second time 72 h later. Controls included animals given a primary C. albicans inoculation in the presence of estrogen (0.02 mg/mouse) (Pri Est) at the time of secondary challenge. At days 3 and 9 postinoculation, 10 mice per group were footpad challenged with CaCF, and DTH was measured 24 h later. Thereafter the mice were sacrificed, and vaginal fungal burdens were determined by quantitative vaginal lavage culture. (A) CFU ± standard errors of the means (SEM) from three experiments. (B) DTH ± SEM from the same mice.
FIG. 4
Effect of C. albicans inocula on induction and maintenance of experimental C. albicans vaginal infections. Animals received the first of weekly subcutaneous injections of estradiol valerate at 0.2 (A) or 0.02 (B) mg/mouse and were inoculated intravaginally 72 h later with various concentrations of C. albicans blastoconidia in a volume of 20 μl of PBS. At days 7, 14, and 21 postinoculation, five to six randomly selected animals per group were sacrificed, and vaginal fungal burdens were determined by quantitative vaginal lavage culture. Shown are CFU ± standard errors of the means (SEM) for two experiments.
FIG. 5
Effect of estrogen withdrawal on maintenance of experimental vaginal C. albicans infections. Two groups of animals were treated with the first of weekly subcutaneous injections of estradiol valerate (0.02 mg/mouse) and were inoculated intravaginally 72 h later. On days 7 and 14 postinoculation, randomly selected animals (5 mice/group/day) were sacrificed, and vaginal fungal burdens were determined by quantitative vaginal lavage culture. For the remaining mice, estrogen treatments were discontinued after day 11 (three injections) in one group, while the other group had two additional treatments (days 18 and 25). Animals were sacrificed on day 32, and vaginal fungal burdens were determined. Shown are CFU ± standard errors of the means (SEM) for two experiments.
FIG. 6
Effects of pseudoestrus on vaginal epithelial-cell-mediated anti-Candida activity. Groups of 10 to 12 mice were treated with 2 weekly subcutaneous injections of estradiol valerate (0.2 mg/mouse) (Est) or sesame seed oil alone (Non-est). Animals were sacrificed, and vaginal epithelial cells were isolated from excised vaginas. Epithelial cells were cultured in triplicate together with C. albicans blastoconidia for 9 h at various E:T ratios in the presence of [3H]glucose. At the conclusion of the culture period, the cultures were harvested and [3H]glucose uptake by C. albicans was determined by liquid scintillation. Each point is the mean percent inhibition ± standard error of the mean (SEM) for three experiments. Asterisks, significant differences (P < 0.05).
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