Transforming growth factor beta (TGFβ) signaling regulates multifaceted reproductive processes. It has been shown that the type 1 receptor of TGFβ (TGFBR1) is indispensable for female reproductive tract development, implantation, placental development, and fertility. However, the role of TGFβ signaling in decidual development and function remains poorly defined. Our objective is to determine the impact of uterine-specific deletion of Tgfbr1 on decidual integrity, with a focus on the cellular and molecular properties of the decidua during development. Our results show that the developmental dynamics of the decidua is altered in TGFBR1 conditionally depleted uteri from embryonic day (E) 5.5 to E8.5, substantiated by downregulation of genes associated with inflammatory responses and uterine natural killer cell abundance, reduced presence of nondecidualized fibroblasts in the antimesometrial region, and altered decidual cell development. Notably, conditional ablation of TGFBR1 results in the formation of decidua containing more abundant alpha smooth muscle actin (ACTA2)-positive cells at the peripheral region of the antimesometrial side versus controls at E6.5–E8.5. This finding is corroborated by upregulation of a subset of smooth muscle marker genes in Tgfbr1 conditionally deleted decidua at E6.5 and E8.5. Moreover, increased cell proliferation and enhanced decidual ERK1/2 signaling were found in Tgfbr1 conditional knockout mice upon decidual regression. In summary, conditional ablation of TGFBR1 in the uterus profoundly impacts the cellular and molecular properties of the decidua. Our results suggest that TGFBR1 in uterine epithelial and stromal compartments is important for the integrity of the decidua, a transient but crucial structure that supports embryo development.

中文翻译：

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转化生长因子β信号和小鼠蜕膜完整性†。

转化生长因子 β (TGFβ) 信号调节多方面的生殖过程。研究表明，TGFβ 1 型受体 (TGFBR1) 对于女性生殖道发育、着床、胎盘发育和生育能力是不可或缺的。然而，TGFβ 信号在蜕膜发育和功能中的作用仍不清楚。我们的目标是确定子宫特异性缺失Tgfbr1的影响关于蜕膜的完整性，重点是发育过程中蜕膜的细胞和分子特性。我们的研究结果表明，蜕膜的发育动态在 TGFBR1 条件性耗尽的子宫中发生了变化，从胚胎日 (E) 5.5 到 E8.5，这通过与炎症反应和子宫自然杀伤细胞丰度相关的基因下调、非蜕膜化成纤维细胞的存在减少得到证实在 antimometrial 区域，并改变了蜕膜细胞的发育。值得注意的是，TGFBR1 的条件性消融导致在 E6.5–E8.5 的逆轴侧周边区域形成含有更丰富的α平滑肌肌动蛋白 (ACTA2) 阳性细胞的蜕膜。Tgfbr1平滑肌标记基因子集的上调证实了这一发现在 E6.5 和 E8.5 有条件地删除蜕膜。此外，在Tgfbr1条件性基因敲除小鼠蜕膜退化后发现细胞增殖增加和蜕膜 ERK1/2 信号增强。总之，子宫中 TGFBR1 的条件性消融深刻影响了蜕膜的细胞和分子特性。我们的结果表明，子宫上皮和间质隔室中的 TGFBR1 对于蜕膜的完整性很重要，蜕膜是一种支持胚胎发育的短暂但至关重要的结构。