College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Int J Mol Sci. 2022 Oct 18;23(20):12494. doi: 10.3390/ijms232012494.
Myometrium plays critical roles in multiple processes such as embryo spacing through peristalsis during mouse implantation, indicating vital roles of smooth muscle in the successful establishment and quality of implantation. Actin, a key element of cytoskeleton structure, plays an important role in the movement and contraction of smooth muscle cells (SMCs). However, the function of peri-implantation uterine smooth muscle and the regulation mechanism of muscle tension are still unclear. This study focused on the molecular mechanism of actin assembly regulation on implantation in smooth muscle. Phalloidin is a highly selective bicyclic peptide used for staining actin filaments (also known as F-actin). Phalloidin staining showed that F-actin gradually weakened in the CD-1 mouse myometrium from day 1 to day 4 of early pregnancy. More than 3 mice were studied for each group. Jasplakinolide (Jasp) used to inhibit F-actin depolymerization promotes F-actin polymerization in SMCs during implantation window and consequently compromises embryo implantation quality. Transcriptome analysis following Jasp treatment in mouse uterine SMCs reveals significant molecular changes associated with actin assembly. Tagln is involved in the regulation of the cell cytoskeleton and promotes the polymerization of G-actin to F-actin. Our results show that Tagln expression is gradually reduced in mouse uterine myometrium from day 1 to 4 of pregnancy. Furthermore, progesterone inhibits the expression of Tagln through the progesterone receptor. Using siRNA to knock down Tagln in day 3 SMCs, we found that phalloidin staining is decreased, which confirms the critical role of Tagln in F-actin polymerization. In conclusion, our data suggested that decreases in actin assembly in uterine smooth muscle during early pregnancy is critical to optimal embryo implantation. Tagln, a key molecule involved in actin assembly, regulates embryo implantation by controlling F-actin aggregation before implantation, suggesting moderate uterine contractility is conducive to embryo implantation. This study provides new insights into how the mouse uterus increases its flexibility to accommodate implanting embryos in the early stage of pregnancy.
子宫肌在多个过程中发挥关键作用，例如在小鼠着床期间通过蠕动来分隔胚胎，这表明平滑肌在着床的成功建立和质量中起着重要作用。肌动蛋白是细胞骨架结构的关键元素，在平滑肌细胞的运动和收缩中发挥重要作用。然而，着床期子宫平滑肌的功能和肌肉张力的调节机制尚不清楚。本研究专注于平滑肌中肌动蛋白组装调节对着床的分子机制。鬼笔环肽是一种高度选择性的双环肽，用于染色肌动蛋白丝（也称为 F-肌动蛋白）。鬼笔环肽染色显示，从妊娠第 1 天到第 4 天，CD-1 小鼠子宫肌中的 F-肌动蛋白逐渐减弱。每个实验组都有超过 3 只小鼠。鬼笔环肽用来抑制 F-肌动蛋白解聚，促进着床窗口期间 SMC 中的 F-肌动蛋白聚合，从而损害胚胎着床质量。在小鼠子宫 SMC 中用 Jasplakinolide（Jasp）处理后的转录组分析揭示了与肌动蛋白组装相关的显著分子变化。Tagln 参与细胞细胞骨架的调节，并促进 G-肌动蛋白向 F-肌动蛋白的聚合。我们的结果显示，从妊娠第 1 天到第 4 天，Tagln 在小鼠子宫肌中的表达逐渐降低。此外，孕激素通过孕激素受体抑制 Tagln 的表达。在第 3 天 SMC 中用 siRNA 敲低 Tagln，我们发现鬼笔环肽染色减少，这证实了 Tagln 在 F-肌动蛋白聚合中的关键作用。总之，我们的数据表明，妊娠早期子宫平滑肌中肌动蛋白组装的减少对于最佳胚胎着床至关重要。Tagln 是肌动蛋白组装的关键分子，通过控制着床前 F-肌动蛋白的聚集来调节胚胎着床，这表明适度的子宫收缩有利于胚胎着床。本研究为小鼠子宫在妊娠早期增加其灵活性以容纳着床胚胎提供了新的见解。
