C/EBPd drives key endocrine signals in human fetal membranes at parturition [RNA-seq]

Amnion-derived prostaglandin E2 (PGE2) and cortisol are key to labor onset. Identification of the common transcription factor driving the expression of both cyclooxygenase-2 (COX-2) and 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1), the key enzymes in their production, may hold the key to the treatment of pre- and post-term labor. Here, we have found that the CCAAT enhancer binding protein d (C/EBPd) is such a transcription factor which underlies the feed-forward induction of COX-2 and 11ß-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/EBPd in amnion increases along with COX-2 and 11ß-HSD1 at term and further increases at parturition. Knockout of C/EBPd in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPd may serve as a novel pharmaceutical target in the amnion for treatment of pre- and post-term labor. Overall design: RNA sequencing of human amnion tissue obtained from TL and TNL patients