Protein profiling underscores immunological functions of uterine cervical mucus plug in human pregnancy

Abstract

The cervical mucus plug (CMP) differs from the cervical secretions of non-pregnant women, and is the ultimate sealant of the uterine cavity during pregnancy. Although several studies have analyzed biochemical properties of large glycoproteins in the CMP, comprehensive information about its protein composition is yet unavailable. We hypothesized that protein profiling of the CMP could provide key clues to its physiological functions in pregnancy. For this purpose, five CMPs obtained from women in labor at term were analyzed by LC-MS/MS. Out of 291 total proteins identified, 137 were detected in two or more samples, which included S100A8, S100A9, and complement proteins (C3, C4a, C4b, C6, C8g). Several proteins, which have not been described in the cervical mucus of non-pregnant women or in cervicovaginal fluids, such as CD81 antigen and pregnancy zone protein, were also identified. Gene ontology analysis of identified proteins showed significant enrichment of 28 biological processes such as ‘activation of plasma proteins involved in acute inflammatory response’ and ‘positive regulation of cholesterol esterification’. We report the proteome of CMPs from pregnant women at term for the first time, and the overall findings strongly suggest an important role for the CMP in the maintenance of pregnancy and parturition.

Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance

“…Patients with a CL 15 mm had a higher rate of positive AF culture [26% (15/57)] than patients with a CL !15 mm [3.8% (13/344)] [220]. It is unclear if a short cervix leads to compromised innate immunity following the loss of the anti-microbial properties of the cervical mucus plug [224][225][226][227][228][229] and predisposes to ascending intra-amniotic infection, or alternatively, if intra-amniotic infection leads to a short cervix.…”

Viral Infection of the Pregnant Cervix Predisposes to Ascending Bacterial Infection

“…Bacterial infections that ascend from the lower FRT are the most common route of uterine infection, and it is not known why some women suffer such infections that threaten pregnancies and fetal survival (15). In a healthy pregnancy, the uterus and growing fetus are protected from ascending infection by the cervix (12, 16) (17). The cervix has a unique role in the FRT in that it actively controls and limits microbial access by the production of mucus, inflammatory cytokines and anti-microbial peptides (AMP)(18) (17).…”

“…In a healthy pregnancy, the uterus and growing fetus are protected from ascending infection by the cervix (12, 16) (17). The cervix has a unique role in the FRT in that it actively controls and limits microbial access by the production of mucus, inflammatory cytokines and anti-microbial peptides (AMP)(18) (17). In non-pregnant women, the cervical mucus is a viscous fluid in the endocervical canal; however after conception the endocervical canal develops a structure called the cervical mucus plug, which is an anatomical and immunological barrier against ascending infection(19).…”

Genome sequencing of the perciform fishLarimichthys croceaprovides insights into stress adaptation

“…These results expand our knowledge of skin mucus secretion and function in fish, highlighting its importance in response to stress. In addition, the mucus proteome shares many proteins with the mucus from humans and other animals (Lee et al 2011; Rodriguez-Pineiro et al 2013). These characteristics thus make L. crocea a pertinent model for studying mucus biology.…”