Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
J Assist Reprod Genet. 2021 Oct;38(10):2641-2650. doi: 10.1007/s10815-021-02277-z. Epub 2021 Oct 31.
Decidualization is critical for embryo implantation and the success of pregnancy; however, the mechanisms underlying this process remain largely unknown.
In the present study, RNA sequencing was used to detect the expression levels of transducer of ERBB2/1(TOB1) in endometrial samples derived from proliferative and secretory phases. A decidualization model was induced using the combination of estrogen (E2) and progestin (P4) in human endometrial stromal cells (HESCs). The cell counting kit-8 assay was used to detect the viability of HESCs. Related proteins were detected by qPCR and western blot.
The results indicated that TOB1 expression was upregulated in the secretory endometrial samples compared with the corresponding expression observed in the proliferative samples. The expression levels of TOB1 and Notch1 were markedly increased in E2P4-treated HESCs compared with those in the control cells. Treatment with E2P4 strongly suppressed the proliferation of HESCs and induced a G-phase cell cycle arrest. These effects were abolished by knockdown of TOB1 or treatment with of the cells with the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester.
Therefore, these findings highlighted an important role for TOB1/Notch signaling in E2P4-induced decidualization in HESCs, which may provide novel targets for improving the endometrial receptivity.
蜕膜化对于胚胎着床和妊娠的成功至关重要，但这一过程的机制仍知之甚少。
本研究采用 RNA 测序技术检测了转导 ERBB2/1（TOB1）在增生期和分泌期子宫内膜样本中的表达水平。采用雌二醇（E2）和孕激素（P4）联合诱导人子宫内膜基质细胞（HESCs）蜕膜化模型。细胞计数试剂盒-8 检测 HESCs 的活力。通过 qPCR 和 Western blot 检测相关蛋白。
结果表明，与增生期相比，TOB1 在分泌期子宫内膜样本中的表达上调。与对照组相比，E2P4 处理的 HESCs 中 TOB1 和 Notch1 的表达水平明显增加。E2P4 处理强烈抑制 HESCs 的增殖，并诱导 G 期细胞周期停滞。这些作用被 TOB1 敲低或 Notch 抑制剂 N-[N-(3,5-二氟苯乙酰基)-1-丙氨酰]-S-苯甘氨酸叔丁酯处理所消除。
因此，这些发现强调了 TOB1/Notch 信号通路在 E2P4 诱导的 HESCs 蜕膜化中的重要作用，这可能为改善子宫内膜容受性提供新的靶点。
