The Cervicovaginal Mucus Barrier

Abstract

Preterm births are a global health priority that affects 15 million babies every year worldwide. There are no effective prognostic and therapeutic strategies relating to preterm delivery, but uterine infections appear to be a major cause. The vaginal epithelium is covered by the cervicovaginal mucus, which is essential to health because of its direct involvement in reproduction and functions as a selective barrier by sheltering the beneficial lactobacilli while helping to clear pathogens. During pregnancy, the cervical canal is sealed with a cervical mucus plug that prevents the vaginal flora from ascending toward the uterine compartment, which protects the fetus from pathogens. Abnormalities of the cervical mucus plug and bacterial vaginosis are associated with a higher risk of preterm delivery. This review addresses the current understanding of the cervicovaginal mucus and the cervical mucus plug and their interactions with the microbial communities in both the physiological state and bacterial vaginosis, with a focus on gel-forming mucins. We also review the current state of knowledge of gel-forming mucins contained in mouse cervicovaginal mucus and the mouse models used to study bacterial vaginosis.

Keywords: bacterial vaginosis; cervical mucus plug; cervix; microbiota; mouse model; mucin.

Figure 1

Women have a large pear-shaped uterine cavity. The transition between the uterus and vagina occurs in the cervical canal between the mucus-secreting endocervical epithelium and the stratified squamous epithelium of the ectocervix. The vagina is lined by a squamous and muscular epithelium that is not keratinized. The mouse uterus is bicornuate. As for the woman, the lower genital tract in the mouse contains the cervix, which includes the endocervix and the ectocervix, and opens into the vaginal cavity. The mouse vaginal epithelium is keratinized.

Figure 2

Oligosaccharide chains of human GFMs. (a) Theoretical O-glycosylation. The backbone is made of repeated units, which are not represented. Among the eight known types of mucin core structure, cores 1–4 are the most common. (b) Examples of the main GFM glycans of cervicovaginal mucus (CVM), which are mainly sialylated and fucosylated. More neutral oligosaccharides than sialylated oligosaccharides are detected at midcycle than at pre- or post-ovulation. The sugar code letter and O-glycan structure are from Kaltner et al. [17].

Figure 3

Hormonal regulation of GFMs in the woman’s genital tract. MUC5B was the main GFM in the woman’s genital tract, and its expression peaked at midcycle. MUC5AC was highly expressed and appeared to have little variation through the menstrual cycle. MUC6 and MUC2 were detected in small amounts. MUC6 was observed during the proliferative and secretory phases, and MUC2 during the secretory phase. AU, arbitrary units.

Figure 4

Bacterial vaginosis in the pregnant woman predisposes to ascending bacterial infection. During a healthy pregnancy, women produce a dense cervical mucus plug (green) that prevents vaginal flora from reaching the uterine cavity (left). During vaginal dysbiosis (right), the depletion of lactobacilli (blue) promotes the proliferation of pathogens in the vagina (red and yellow), which can more easily reach the uterine compartment if the cervical mucus plug (CMP) is smaller and/or too porous.