N-glycosylation of cervicovaginal fluid reflects microbial community, immune activity, and pregnancy status

Human cervicovaginal fluid (CVF) is a complex, functionally important and glycan rich biological fluid, fundamental in mediating physiological events associated with reproductive health. Using a comprehensive glycomic strategy we reveal an extremely rich and complex N-glycome in CVF of pregnant and non-pregnant women, abundant in paucimannose and high mannose glycans, complex glycans with 2-4 N-Acetyllactosamine (LacNAc) antennae, and Poly-LacNAc glycans decorated with fucosylation and sialylation. N-glycosylation profiles were observed to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome. Compared to CVF from women experiencing term birth, CVF from women who subsequently experienced preterm birth showed lower sialylation, which correlated to the presence of a diverse microbiome, and higher fucosylation, which correlated positively to pro-inflammatory cytokine concentration. This study is the first step towards better understanding the role of cervicovaginal glycans in reproductive health, their contribution to the mechanism of microbial driven preterm birth, and their potential for preventative therapy.

Automated summary

This study used a comprehensive glycomic strategy to reveal the complex and abundant N-glycome in cervicovaginal fluid (CVF) of pregnant and non-pregnant women. The N-glycosylation profiles were found to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome. Additionally, lower sialylation and higher fucosylation were observed in CVF from women who subsequently experienced preterm birth, indicating their potential roles in the mechanism of microbial driven preterm birth.