Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, P.R. China.
Clin Transl Med. 2021 Jun;11(6):e416. doi: 10.1002/ctm2.416.
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 11β-hydroxysteroid dehydrogenase 1 (11β-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 δ (C/EBPδ) is such a transcription factor which underlies the feed-forward induction of COX-2 and 11β-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/EBPδ in the amnion increases along with COX-2 and 11β-HSD1 at term and further increases at parturition. Knockout of C/EBPδ in mice delays the onset of labor further supporting the concept. In conclusion, C/EBPδ pathway may be speculated to serve as a potential pharmaceutical target in the amnion for treatment of pre-term labor.
羊膜衍生的前列腺素 E2（PGE2）和皮质醇是分娩开始的关键。鉴定一种共同的转录因子，驱动其产生的关键酶环氧化酶-2（COX-2）和 11β-羟类固醇脱氢酶 1（11β-HSD1）的表达，可能是治疗早产的关键。在这里，我们发现 CCAAT 增强子结合蛋白 δ（C/EBPδ）就是这样一种转录因子，它通过自身产物 PGE2 和皮质醇在人羊膜成纤维细胞中对 COX-2 和 11β-HSD1 表达进行正反馈诱导，从而确保羊膜中分娩所需的产物的产生。此外，C/EBPδ 在足月时与 COX-2 和 11β-HSD1 一起增加，并在分娩时进一步增加。在小鼠中敲除 C/EBPδ 进一步支持了这一概念，即进一步延迟了分娩的开始。总之，C/EBPδ 通路可能被推测为羊膜中用于治疗早产的潜在药物靶点。
