Hyposecretion of cervical MUC5B is related to preterm birth in pregnant women after cervical excisional surgery.

Abstract

Excisional surgery for cervical intraepithelial neoplasia is a risk factor for preterm birth in subsequent pregnancies. However, the underlying mechanisms of this association remain unclear. We previously showed that cervical MUC5B, a mucin protein, may be a barrier to ascending pathogens during pregnancy. We thus hypothesized that hyposecretion of cervical MUC5B is associated with preterm birth after cervical excisional surgery. This prospective nested case-control study (Study 1) included pregnant women who had previously undergone cervical excisional surgery across 11 hospitals. We used proteomics to compare cervicovaginal fluid at 18-22weeks of gestation between the preterm and term birth groups. In another case-control analysis (Study 2), we compared MUC5B expression in nonpregnant uterine tissues between 15 women with a history of cervical excisional surgery and 26 women without a history of cervical surgery. The abundance of MUC5B in cervicovaginal fluid was significantly decreased in the preterm birth group (fold change=0.41, p=.035). Among the 480 quantified proteins, MUC5B had the second highest positive correlation with gestational age at delivery in the combined preterm and term groups. The cervicovaginal microbiome composition was not significantly different between the two groups. Cervical length was not correlated with gestational age at delivery (r=0.18, p=.079). Histologically, the MUC5B-positive area in the nonpregnant cervix was significantly decreased in women with a history of cervical excisional surgery (0.85-fold, p=.048). The distribution of MUC5B-positive areas in the cervical tissues of 26 women without a history of cervical excisional surgery differed across individuals. This study suggests that the primary mechanism by which cervical excisional surgery causes preterm birth is the hyposecretion of MUC5B due to loss of the cervical glands.