CONICET, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales IQUIBICEN, Buenos Aires, Argentina.
Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany.
Reprod Biomed Online. 2023 Nov;47(5):103289. doi: 10.1016/j.rbmo.2023.103289. Epub 2023 Jul 19.
Do microRNAs (miRNAs) play a role in regulating endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) in decidualized cells and endometrium associated with reproductive failures?
Endometrial stromal cell line St-T1b was decidualized in vitro with 8-Br-cAMP over 5 days, or treated with the ERS inducer thapsigargin. Expression of ERS sensors, UPR markers and potential miRNA regulators was analysed by quantitative PCR. Endometrial biopsies from patients with recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) were investigated for the location of miRNA expression.
Decidualization of St-T1b cells resulted in increased expression of ERS sensors including ATF6α, PERK and IRE1α, and the UPR marker, CHOP. TXNIP, which serves as a link between the ERS pathway and inflammation, as well as inflammasome NLRP3 and interleukin 1β expression increased in decidualized cells. An in-silico analysis identified miR-17-5p, miR-21-5p and miR-193b-3p as miRNAs potentially involved in regulation of the ERS/UPR pathways and inflammation associated with embryo implantation. Their expression decreased significantly (P ≤ 0.0391) in non-decidualized cells in the presence of thapsigargin. Finally, expression of the selected miRNAs was localized by in-situ hybridization in stromal and glandular epithelial cells in endometrial samples from patients with RPL and RIF. Expression in stroma cells from patients with RPL was lower in comparison with stroma cells from patients with RIF.
Decidualization in St-T1b cells is accompanied by ERS/UPR processes, associated with an inflammatory response that is potentially influenced by miR-17-5p, miR-21-5p and miR-193b-3p. These miRNAs are expressed differentially in stromal cells from patients with RPL and RIF, indicating an alteration in regulation of the ERS/UPR pathways.
微小 RNA（miRNAs）是否在调节胚胎着床失败相关的蜕膜化细胞和子宫内膜中的内质网应激（ERS）和未折叠蛋白反应（UPR）中发挥作用？
将体外培养的子宫内膜基质细胞系 St-T1b 用 8-Br-cAMP 诱导 5 天以实现蜕膜化，或用 ERS 诱导剂他普西醌处理。通过定量 PCR 分析 ERS 传感器、UPR 标志物和潜在的 miRNA 调节因子的表达。研究复发性流产（RPL）和复发性种植失败（RIF）患者的子宫内膜活检标本以确定 miRNA 表达的位置。
St-T1b 细胞的蜕膜化导致 ERS 传感器包括 ATF6α、PERK 和 IRE1α 以及 UPR 标志物 CHOP 的表达增加。TXNIP 作为 ERS 途径与炎症之间的联系，以及炎症小体 NLRP3 和白细胞介素 1β 的表达在蜕膜化细胞中增加。通过计算机分析发现 miR-17-5p、miR-21-5p 和 miR-193b-3p 作为可能参与胚胎着床相关的 ERS/UPR 途径和炎症调节的 miRNA。在存在他普西醌的情况下，非蜕膜化细胞中的这些 miRNA 的表达显著降低（P ≤ 0.0391）。最后，通过原位杂交在 RPL 和 RIF 患者的子宫内膜样本中的基质和腺上皮细胞中定位所选 miRNA 的表达。与 RIF 患者的基质细胞相比，RPL 患者的基质细胞中这些 miRNA 的表达较低。
St-T1b 细胞的蜕膜化伴随着 ERS/UPR 过程，伴随着潜在受 miR-17-5p、miR-21-5p 和 miR-193b-3p 影响的炎症反应。这些 miRNA 在 RPL 和 RIF 患者的基质细胞中的表达存在差异，表明 ERS/UPR 途径的调节发生改变。
