PDF(Pubmed)
Abstract：
Male and female reproductive tracts develop from anterior intermediate mesoderm with similar differentiation processes. The anterior intermediate mesoderm develops into the mesonephros, and the Wolffian duct initiates by epithelialization in the mesonephros. The Müllerian duct invaginates from the coelomic epithelium of the cranial mesonephros for ductal formation and is then regionalized into proximal to caudal female reproductive tracts. In this study, we focused on the epithelialization of the Wolffian duct, initiation of the Müllerian duct, and the regionalization step of the Müllerian ducts as a continuous process. By using intermediate mesodermal cells from mouse pluripotent stem cells, we identified that inhibition of SMAD2/3 signaling might be involved in the differentiation into mesenchymal cells, after which mesonephric cells might be then epithelialized during differentiation of the Wolffian duct. Aggregation of coelomic epithelial cells might be related to initiation of the Müllerian duct. Transcriptomic analysis predicted that consensus sequences of SMAD3/4 were enriched among highly expressed genes in the proximal Müllerian duct. SMAD2/3 signaling to regulate differentiation of the Wolffian duct was continuously activated in the proximal Müllerian duct and was involved in proximal and oviductal regionalization. Therefore, SMAD2/3 signaling may be finely tuned to regulate differentiation from initiation to regionalization steps.
摘要：
男性和女性生殖道从前中间中胚层发育，分化过程相似。前中间中胚层发育成中肾,沃尔夫导管通过中肾上皮化启动。Müllerian导管从颅中肾的腔上皮侵入以形成导管，然后将其区域化为尾雌性生殖道的近端。在这项研究中,我们专注于沃尔夫导管的上皮化，穆勒导管的起始，以及苗勒管的区域化步骤是一个连续过程。通过使用小鼠多能干细胞的中间中胚层细胞，我们发现SMAD2/3信号的抑制可能参与分化为间充质细胞，之后，中肾细胞可能在Wolffian导管分化过程中被上皮化。体腔上皮细胞的聚集可能与苗勒管的启动有关。转录组学分析预测SMAD3/4的共有序列在Müller导管近端高表达基因中富集。调节Wolffian导管分化的SMAD2/3信号在Müller近端导管中连续激活，并参与近端和输卵管区域化。因此,可以精细地调节SMAD2/3信号传导以调节从起始到区域化步骤的分化。
