Zhang Huakun, Wu Zhengzhong, Yang Ningjie, Wu Shuhua, Fan Jing, Wang Ping, Li Xuemei
Reproductive Medicine Center, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, Guangdong Province, 518000, China.
Department of Reproductive Immunology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, Guangdong Province, 518000, China.
Adv Biol (Weinh). 2025 Feb;9(2):e2400279. doi: 10.1002/adbi.202400279. Epub 2024 Dec 18.
Recurrent implantation failure (RIF) is characterized by the repeated failure of implantation, often linked to impaired endometrial receptivity. This study investigates how granulocyte colony-stimulating factor (G-CSF) promotes endometrial stromal cell decidualization.
THESCs (human telomerase reverse transcriptase-immortalized endometrial stromal cells) were used as an in vitro cell model to induce decidualization. The effects of G-CSF on the expression of decidualization genes and apoptosis during decidualization were examined. Additionally, a chemical inhibitor of signal transducer and activator of transcription 3 (STAT3) and the small interfering RNA (siRNA) targeting Homeobox A10 (Hoxa10) were employed to explore the involvement of the STAT3/HOXA10 axis in the action of G-CSF.
G-CSF promoted decidualization markers expression and suppressed apoptosis in THESCs Treatment with G-CSF enhanced STAT3 activation during decidualization induction. STAT3 inhibition diminished the effects of G-CSF on decidualization marker expression and apoptosis suppression. Furthermore, it was demonstrated that G-CSF increased Hoxa10 expression in a STAT3-dependent manner. Silencing Hoxa10 abrogated the effects of G-CSF on promoting decidualization.
G-CSF enhances decidualization of endometrial stromal cells via STAT3/HOXA10 axis activation. These findings suggest that optimal G-CSF delivery strategies could improve endometrial receptivity in RIF patients.
反复种植失败(RIF)的特征是反复种植失败,通常与子宫内膜容受性受损有关。本研究调查粒细胞集落刺激因子(G-CSF)如何促进子宫内膜基质细胞蜕膜化。
使用人端粒酶逆转录酶永生化子宫内膜基质细胞(THESCs)作为体外细胞模型来诱导蜕膜化。检测G-CSF对蜕膜化过程中蜕膜化基因表达和细胞凋亡的影响。此外,使用信号转导和转录激活因子3(STAT3)的化学抑制剂以及靶向同源盒A10(Hoxa10)的小干扰RNA(siRNA)来探讨STAT3/Hoxa10轴在G-CSF作用中的参与情况。
G-CSF促进THESCs中蜕膜化标志物的表达并抑制细胞凋亡。在诱导蜕膜化过程中,G-CSF处理增强了STAT3的激活。抑制STAT3可减弱G-CSF对蜕膜化标志物表达和细胞凋亡抑制的作用。此外,证明G-CSF以STAT3依赖的方式增加Hoxa10的表达。沉默Hoxa10可消除G-CSF促进蜕膜化的作用。
G-CSF通过激活STAT3/Hoxa10轴增强子宫内膜基质细胞的蜕膜化。这些发现表明,优化的G-CSF递送策略可以改善RIF患者的子宫内膜容受性。