C/EBPδ drives key endocrine signals in the human amnion at parturition

Amnion-derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of a common transcription factor driving the expression of both cyclooxygenase-2 (COX-2) and 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1), the key enzymes in their production, may hold the key to the treatment of pre-term labor. Here, we have found that the CCAAT enhancer binding protein delta (C/EBP delta) is such a transcription factor which underlies the feed-forward induction of COX-2 and 11 beta-HSD1 expression by their own products PGE2 and cortisol in human amnion fibroblasts so that their production would be ensured in the amnion for the onset of labor. Moreover, the abundance of C/EBP delta in the amnion increases along with COX-2 and 11 beta-HSD1 at term and further increases at parturition. Knockout of C/EBP delta in mice delays the onset of labor further supporting the concept. In conclusion, C/EBP delta pathway may be speculated to serve as a potential pharmaceutical target in the amnion for treatment of pre-term labor.

Automated summary

The transcription factor C/EBPδ plays a critical role in inducing the expression of COX-2 and 11β-HSD1 in human amnion fibroblasts, ensuring their production for labor onset. The abundance of C/EBPδ in the amnion increases at term and further at parturition, with knockout of C/EBPδ in mice delaying the onset of labor. These findings suggest that the C/EBPδ pathway may serve as a potential pharmaceutical target for the treatment of pre-term labor.