PDF(Pubmed)
Abstract：
Pregnancy involving intricate tissue transformations governed by the progesterone hormone (P4). P4 signaling via P4 receptors (PRs) is vital for endometrial receptivity, decidualization, myometrial quiescence, and labor initiation. This study explored the role of TCF23 as a downstream target of PR during pregnancy. TCF23 was found to be expressed in female reproductive organs, predominantly in uterine stromal and smooth muscle cells. Tcf23 expression was high during midgestation and was specifically regulated by P4, but not estrogen. The Tcf23 knockout (KO) mouse was generated and analyzed. Female KO mice aged 4-6 months exhibited subfertility, reduced litter size, and defective parturition. Uterine histology revealed disrupted myometrial structure, altered collagen organization, and disarrayed smooth muscle sheets at the conceptus sites of KO mice. RNA-Seq analysis of KO myometrium revealed dysregulation of genes associated with cell adhesion and extracellular matrix organization. TCF23 potentially modulates TCF12 activity to mediate cell-cell adhesion and matrix modulation in smooth muscle cells. Overall, TCF23 deficiency leads to impaired myometrial remodeling, causing parturition delay and fetal demise. This study sheds light on the critical role of TCF23 as a dowstream mediator of PR in uterine remodeling, reflecting the importance of cell-cell communication and matrix dynamics in myometrial activation and parturition.
摘要：
妊娠涉及由孕酮激素（P4）控制的复杂组织转化。通过P4受体（PRs）的P4信号对子宫内膜容受性至关重要，判定化，子宫肌层静止，和劳动启动。本研究探讨了TCF23作为妊娠期间PR的下游靶标的作用。发现TCF23在女性生殖器官中表达，主要存在于子宫间质和平滑肌细胞。Tcf23在妊娠中期表达较高，并受P4而非雌激素特异性调节。产生并分析Tcf23敲除(KO)小鼠。4-6月龄的雌性KO小鼠表现出低生育力，减少产仔数，和有缺陷的分娩。子宫组织学显示子宫肌层结构破坏，改变胶原蛋白组织，并在KO小鼠的概念部位排列平滑肌片。KO子宫肌层的RNA-Seq分析显示与细胞粘附和细胞外基质组织相关的基因失调。TCF23可能调节TCF12活性以介导平滑肌细胞中的细胞-细胞粘附和基质调节。总的来说,TCF23缺乏导致子宫肌层重塑受损，导致分娩延迟和胎儿死亡.这项研究揭示了TCF23作为PR的下游介质在子宫重塑中的关键作用，反映了细胞间通讯和基质动力学在子宫肌层激活和分娩中的重要性。
