Senolytic treatment modulates decidualization in human endometrial stromal cells
Senolytic treatment modulates decidualization in human endometrial stromal cells
复制标题
DOI：
10.1016/j.bbrc.2021.07.075
复制
发表时间：
2021-07-27
影响因子：
3.1
通讯作者：
Tamura, Kazuhiro
中科院分区：
文献类型：
--
作者：
Kusama, Kazuya;Yamauchi, Naoya;Tamura, Kazuhiro
子宫内膜间质细胞（ESCs）向蜕膜细胞的分化是成功胚胎着床和胎盘的关键步骤，始于月经周期的分泌期。在去个性化过程中，ESCs经历增殖阻滞并分泌炎症介质，包括衰老相关分泌表型（SASP）。虽然一些抗衰老药物可以改善与年龄相关的疾病，但它们对脱个体化ESCs细胞衰老的影响尚未被探索。为此，我们使用抗衰老药物槲皮素（Que）、达沙替尼（Das）和BPTES治疗去个体化ESCs。Que减少了衰老相关β -半乳糖苷酶（sa - β -gal）阳性细胞的数量和衰老标志物在蜕膜刺激（二丁基camp +孕酮：DP）处理的ESCs中的表达。同时，Que显著增加了去个位化标志物IGFBP1、PRL和FOXO1在去个位化ESCs中的表达。与Que类似，Das也刺激了去个体化。与Que或Das单独处理相比，Que和Das联合处理协同增加了脱个体化标志物和衰老标志物的表达。然而，BPTES并没有增强去个体化标志物的表达。这些结果表明，Que和/或Das处理可以去除衰老的蜕膜细胞，并增强其余ESCs的蜕膜化。因此，对ESC异常脱个体化的衰老调节可以减轻子宫内膜容受性和胚胎着床功能障碍引起的不孕症。(C) 2021年由Elsevier Inc.出版。
Decidualization - the differentiation of endometrial stromal cells (ESCs) into decidual cells - is a crucial step for successful embryo implantation and placentation that is initiated in the secretory phase of the menstrual cycle. During decidualization, ESCs undergo proliferation arrest and secrete inflammatory mediators, including senescence-associated secretory phenotype (SASP). Although several senolytic agents improve age-related diseases, their effects on cellular senescence in decidualizing ESCs has not been explored. To do this, we treated decidualized ESCs with the senolytic agents Quercetin (Que), Dasatinib (Das), and BPTES. Que decreased the number of senescence-associated beta-galactosidase (SA-beta-Gal) positive cells and expression of senescence markers in ESCs treated with the decidual stimulus (dibutyryl-cAMP plus progesterone: DP). Concomitantly, Que markedly increased the expression of the decidualization markers IGFBP1, PRL, and FOXO1, in decidualizing ESCs. Similar to Que, Das also stimulated decidualization. Treatment with a combination of Que and Das synergistically increased the expression of decidualization markers and senescence markers compared with treatment with Que or Das alone. However, BPTES did not enhance the expression of decidualization markers. These results imply that treatment with Que and/or Das can remove senescent decidual cells and enhance the decidualization of the rest of ESCs. Thus, senolytic modulation of abnormal ESC decidualization could alleviate infertility caused by dysfunctions of endometrial receptivity and embryo implantation. (C) 2021 Published by Elsevier Inc.