The Non-pregnant and Pregnant Human Cervix: a Systematic Proteomic Analysis

Appropriate timing of cervical remodeling (CR) is key to normal term parturition. To date, mechanisms behind normal and abnormal (premature or delayed) CR remain unclear. Recent studies show regional differences exist in human cervical tissue structure. While the entire cervix contains extracellular matrix (ECM), the internal os is highly cellular containing 50-60% cervical smooth muscle (CSM). The external os contains 10-20% CSM. Previously, we reported ECM rigidity and different ECM proteins influence CSM cell function, highlighting the importance of understanding not only how cervical cells orchestrate cervical ECM remodeling in pregnancy, but also how changes in specific ECM proteins can influence resident cellular function. To understand this dynamic process, we utilized a systematic proteomic approach to understand which soluble ECM and cellular proteins exist in the different regions of the human cervix and how the proteomic profiles change from the non-pregnant (NP) to the pregnant (PG) state. We found the human cervix proteome contains at least 4548 proteins and establish the types and relative abundance of cellular and soluble matrisome proteins found in the NP and PG human cervix. Further, we report the relative abundance of proteins involved with elastic fiber formation and ECM organization/degradation were significantly increased while proteins involved in RNA polymerase I/promoter opening, DNA methylation, senescence, immune system, and compliment activation were decreased in the PG compared to NP cervix. These findings establish an initial platform from which we can further comprehend how changes in the human cervix proteome results in normal and abnormal CR.

Automated summary

Appropriate timing of cervical remodeling is important for normal term parturition. Recent studies have shown regional differences in human cervical tissue structure and the distribution of extracellular matrix (ECM) and cervical smooth muscle (CSM) cells. This study used a systematic proteomic approach to identify the soluble ECM and cellular proteins in different regions of the human cervix and compare the proteomic profiles between non-pregnant and pregnant states. The findings suggest that the abundance of proteins involved in elastic fiber formation and ECM organization/degradation increases, while proteins involved in RNA polymerase I/promoter opening, DNA methylation, senescence, immune system, and complement activation decrease in the pregnant cervix compared to the non-pregnant cervix.