Department of Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University, Νo. 1 Jianshe East Road, Henan, 450000, Zhengzhou, PR China.
Department of Reproductive Medical Center, Jiaozuo Maternity and Child Health Hospital, Jiaozuo, China.
Diagn Pathol. 2021 May 16;16(1):44. doi: 10.1186/s13000-021-01104-4.
Impaired endometrial receptivity is a major reason for embryo implantation failure. There's a paucity of information regarding the role of circRNAs on endometrial receptivity. Here, we investigated the function of hsa_circ_001946 on endometrial receptivity and its mechanisms.
A total of 50 women composing 25 with recurrent implantation failure and 25 who conceived after their implantation were recruited in this study. Expression of hsa_circ_001946, miR-135b, and HOXA10 was evaluated by quantitative RT-PCR (qRT-PCR) in biopsied endometrial tissue samples. The levels of HOXA10, and cell cycle markers (CCNB1, CDK1, and CCND1) were determined by IHC and western blotting assays. Binding relationship among miR-135b, hsa_circ_001946 and HOXA10 were confirmed by dual luciferase reporter assays and western blotting. MTT assays and cell cycle assays by FACS were employed to evaluate the proliferation and cell cycle of cells. T-HESCs were cultured with 1 µM medroxyprogesterone acetate (MPA) and 0.5 mM 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP) to induce decidualization. The mechanisms and functions of hsa_circ_001946 on decidualization were further assessed by qRT-PCR evaluating the expression of hsa_circ_001946, miR-135b, HOXA10 and decidual markers (PRL and IGFBP1) in T-HESCs.
Endometrial tissues from patients with recurrent implantation failure had lower hsa_circ_001946 expression, higher miR-135b expression, and lower HOXA10 expression. Hsa_circ_001946 promoted HOXA10 expression by sponging miR-135b in T-HESCs. Overexpression of hsa_circ_001946 restored cell proliferation and cell cycle that were disrupted by miR-135b overexpression in T-HESCs. Decidualized T-HESCs had higher hsa_circ_001946 expression, lower miR-135b expression, and higher HOXA10 expression. Overexpression of hsa_circ_001946 reversed the expression of decidual markers (PRL and IGFBP1) that were suppressed by miR-135b overexpression in T-HESCs.
In conclusion, our findings suggest that hsa_circ_001946 promotes cell proliferation and cell cycle process and increases expression of decidualization markers to enhance endometrial receptivity progression via sponging miR-135b and elevating HOXA10.
子宫内膜容受性受损是胚胎着床失败的主要原因。关于环状 RNA（circRNAs）对子宫内膜容受性的作用，信息仍然匮乏。在这里，我们研究了 hsa_circ_001946 对子宫内膜容受性的作用及其机制。
本研究共招募了 50 名女性，其中 25 名患有复发性着床失败，25 名成功妊娠。通过定量 RT-PCR（qRT-PCR）检测子宫内膜活检组织样本中 hsa_circ_001946、miR-135b 和 HOXA10 的表达。通过免疫组化和 Western blot 检测 HOXA10 和细胞周期标志物（CCNB1、CDK1 和 CCND1）的水平。通过双荧光素酶报告基因检测和 Western blot 验证 miR-135b、hsa_circ_001946 和 HOXA10 之间的结合关系。通过 MTT 检测和细胞周期检测（流式细胞术）评估细胞的增殖和细胞周期。通过 qRT-PCR 检测 T-HESCs 中 hsa_circ_001946、miR-135b、HOXA10 和蜕膜化标记物（PRL 和 IGFBP1）的表达，进一步评估 hsa_circ_001946 在蜕膜化中的作用和功能。
复发性着床失败患者的子宫内膜组织中 hsa_circ_001946 表达降低，miR-135b 表达升高，HOXA10 表达降低。hsa_circ_001946 通过海绵吸附 miR-135b 促进 T-HESCs 中 HOXA10 的表达。hsa_circ_001946 的过表达可恢复因 miR-135b 过表达而受损的 T-HESCs 的细胞增殖和细胞周期。蜕膜化的 T-HESCs 中 hsa_circ_001946 表达升高，miR-135b 表达降低，HOXA10 表达升高。hsa_circ_001946 的过表达可逆转因 miR-135b 过表达而受抑制的蜕膜化标记物（PRL 和 IGFBP1）在 T-HESCs 中的表达。
总之，我们的研究结果表明，hsa_circ_001946 通过海绵吸附 miR-135b 并上调 HOXA10 来促进细胞增殖和细胞周期进程，并增加蜕膜化标记物的表达，从而增强子宫内膜容受性进展。
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