The role of IL-15 on vulvovaginal candidiasis in mice and related adverse pregnancy outcomes

Abstract

Vulvovaginal candidiasis (VVC), a major gynecological disease with high recurrence rate, increases the risk of abortion, intrauterine infection, premature rupture of membranes, and premature birth in pregnancy. However, the exact pathogenesis of this disease has yet to be elucidated. To facilitate understanding of the pathogenesis of VVC in pregnancy, this study sought to establish an animal model of vaginal infection with Candida albicans in pregnant mice. Female mice were mated with male mice, and female mice were infected with C. albicans at E4.5 (embryonic day 4.5). The weight and abortion rate of pregnant mice at E0.5, E4.5, E8.5, E11.5, and E18.5 were recorded, respectively, as well as the weights of fetus and placenta on E18.5. Fetal weight at E18.5 and the weight growth rate in the experimental mice was lower than those in the control mice, but the placenta weight at E18.5 and the abortion rate in the experimental mice were increased with those of the control mice. Hematoxylin-eosin (H&E) staining, Gomori-Grocott staining and vaginal lavage culturing were conducted to verify that the experimental mice were infected with C. albicans. Differentially expressed gene IL-15 was screened out by polymerase chain reaction (PCR) array between the two groups. Enzyme-linked immunosorbent assay (ELISA) showed that IL-15 expression in plasma of the mice was decreased in the experimental group compared with the control group. RT-qPCR confirmed that IL-15 mRNA expression was increased in placental tissues, while mRNA expression of IL-15R/JAK1-JAK3/PI3K/PDK1/AKT/P70S6K-mTOR was decreased in placental tissues. In conclusion, this study demonstrated that VVC in BALB/c pregnant mice led to a series of adverse pregnancy outcomes that were related to changes in IL-15 and its downstream signaling pathways, which may indicate a potential therapy for VVC during pregnancy in humans.

Keywords: Candida albicans; IL-15; Inflammation; Pregnancy; Vulvovaginal candidiasis.