Myometrial activation: Novel concepts underlying labor.

Area of Science:

• Reproductive biology
• Immunology
• Molecular endocrinology

Background:

• Term labor is a physiological inflammatory process involving fetal and maternal uterine tissues.
• Increased cytokine and chemokine secretion by fetal membranes and uterine tissues precedes and accompanies labor onset.
• Leukocyte infiltration into the uterus, mediated by inflammatory signals, is crucial for labor initiation.

Purpose of the Study:

• To review known mechanisms regulating human term labor onset.
• To highlight the roles of progesterone signaling and cytokine signaling in myometrial activation.
• To discuss the potential for developing new therapeutics for preterm birth prevention.

Main Methods:

• Literature review of molecular mechanisms regulating human labor.
• Analysis of cytokine and chemokine signaling pathways.
• Examination of progesterone and progesterone receptor (PRA/B) roles.
• Investigation of the activator protein-1 (AP-1) mediated pathway in progesterone withdrawal.

Main Results:

• Term labor is orchestrated by a physiological inflammatory state.
• Pro-inflammatory cytokines and chemokines activate leukocytes and endothelium, facilitating uterine infiltration.
• Leukocyte-secreted matrix metalloproteinases induce cervical ripening and membrane rupture.
• Progesterone withdrawal, mediated by the AP-1 pathway, is critical for myometrial activation and labor contractions.

Conclusions:

• Myometrial activation and labor onset are linked to progesterone changes and cytokine signaling.
• Local functional progesterone withdrawal in the myometrium is supported by recent data.
• Understanding these molecular mechanisms can aid in developing therapies to prevent preterm birth.