1. Comparison of key events involved in normal parturition and inflammation-induced parturition.
Comparison of key events involved in normal parturition and inflammation-induced parturition. Normal parturition is initiated by the increased placental synthesis of CRH at term, which causes the production of cortisol. Cortisol induces the production of prostaglandin E2 and prostaglandin F2α and works in a positive-feedback loop to further stimulate placental CRH production. Prostaglandins induce the production of matrix metalloproteases, which facilitate membrane rupture and cervical remodeling. In concert, activation of the fetal HPA axis leads to a functional progesterone withdrawal and production of contraction-associated proteins, which cause myometrial activation and uterine contractility. During chorioamnionitis, inflammatory cytokines and chemokines produced in response to microbial invasion of the chorioamnion and/or amniotic fluid stimulate prostaglandin production and neutrophil infiltration, leading to the synthesis of matrix metalloproteases and subsequent membrane weakening. Recognition of pathogen-associated molecular patterns by pattern recognition receptors (such as TLRs) is critical for the initiation of inflammation-induced parturition. CAPs, contraction-associated proteins; CRH, corticotropin-releasing hormone; HPA, hypothalamic-pituitary-adrenal; MMPs, matrix metalloproteases; NF-κB, nuclear factor kappa B; PGDH, prostaglandin dehydrogenase; PGs, prostaglandins; PGS2, prostaglandin-endoperoxide synthase 2; TLR, Toll-like receptor. The direction of the arrows within boxes represents either an increase or a decrease in expression.
Emma L. Sweeney et al. Clin. Microbiol. Rev. 2017; doi: /CMR