Systems-level proteomic profiling reveals modular control of human cervical remodeling during pregnancy†

Area of Science:

• Reproductive biology and proteomics.
• Human pregnancy and parturition research.

Background:

• Cervical remodeling (CR) is vital for pregnancy and childbirth, but its molecular mechanisms in humans are not fully understood.
• Existing knowledge lacks a detailed, longitudinal proteomic view of human CR throughout gestation.

Purpose of the Study:

• To create a high-resolution, longitudinal proteomic atlas of human cervical remodeling during normal pregnancy.
• To identify key molecular events and regulatory proteins driving CR across different gestational stages.

Main Methods:

• Retrospective analysis of cervical tissue samples from non-pregnant and pregnant individuals across three trimesters.
• Proteomic profiling using data-independent acquisition mass spectrometry.
• Comparative proteomic analysis, unsupervised clustering, collagen characterization, and protein-protein interaction network construction.

Main Results:

• Quantified 6092 proteins, identifying stage-specific changes in immune regulation, extracellular matrix remodeling, and hormone responsiveness.
• Revealed collagen disruption and coordinated remodeling of hyaluronan, enzymes, and elastic fibers.
• Identified fibronectin 1 (FN1), matrix-metalloproteases 9 (MMP9), and estrogen receptor 1 (ESR1) as central regulators of CR.

Conclusions:

• Established a comprehensive proteomic framework for understanding human cervical remodeling during gestation.
• Provided insights into progesterone withdrawal mechanisms and identified key protein regulators.
• Highlighted potential novel targets for predicting and managing CR disorders.