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在种植窗期复发性种植失败患者中 miR-30d-5p 和 SOCS1 的表达及意义。

Expression and significance of miR-30d-5p and SOCS1 in patients with recurrent implantation failure during implantation window.

机构信息

Reproductive Medical Center, Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

出版信息

Reprod Biol Endocrinol. 2021 Sep 8;19(1):138. doi: 10.1186/s12958-021-00820-2.

Abstract

BACKGROUND

Poor endometrial receptivity is a major factor that leads to recurrent implantation failure. However, the traditional method cannot accurately evaluate endometrial receptivity. Various studies have indicated that microRNAs (miRNAs) are involved in multiple processes of embryo implantation, but the role of miRNAs in endometrial receptivity in patients with recurrent implantation failure (RIF) remains elusive. In the present study, we investigated the presence of pinopodes and the roles of miR-30d-5p, suppressor of cytokine signalling 1 (SOCS1) and the leukaemia inhibitory factor (LIF) pathway in women with a history of RIF during the implantation window.

METHODS

Endometrial tissue samples were collected between January 2018 to June 2019 from two groups of women who underwent in vitro fertilisation and embryo transfer (IVF-ET) or frozen ET. The RIF group included 20 women who underwent ≥ 3 ETs, including a total of ≥ 4 good-quality embryos, without pregnancy, whereas the control group included 10 women who had given birth at least once in the past year. An endometrial biopsy was performed during the implantation window (LH + 7). The development of pinopodes in the endometrial biopsy samples from all groups was evaluated using scanning electron microscopy (SEM). Quantitative reverse transcription-polymerase chain reaction and western blotting were used to investigate the expression levels of miR-30d-5p, SOCS1, and the LIF pathway.

RESULTS

The presence of developed pinopodes decreased in patients with RIF on LH + 7. The expression level of miR-30d-5p decreased in the endometria during the implantation window of patients with RIF, whereas the mRNA and protein levels of SOCS1 were significantly higher in the RIF group than in the control group. Furthermore, a negative correlation was observed between the expression of miR-30d-5p and SOCS1 (r = 0.8362). In addition, a significant decrease in LIF and p-STAT3 expression was observed during the implantation window in patients with RIF.

CONCLUSIONS

MiR-30d-5p and SOCS1 may be potential biomarkers for endometrial receptivity. Changes in pinopode development and abnormal expression of miR-30d-5p, SOCS1 and LIF pathway in the endometrium could be the reasons for implantation failure.

摘要

背景

子宫内膜容受性差是导致反复着床失败的主要因素。然而,传统方法无法准确评估子宫内膜容受性。多项研究表明 microRNAs(miRNAs)参与胚胎着床的多个过程,但 miRNA 在反复着床失败(RIF)患者子宫内膜容受性中的作用仍不清楚。本研究探讨了着床窗期反复着床失败患者中存在的指状突起以及 miR-30d-5p、细胞因子信号转导抑制因子 1(SOCS1)和白血病抑制因子(LIF)通路的作用。

方法

2018 年 1 月至 2019 年 6 月,从接受体外受精和胚胎移植(IVF-ET)或冷冻胚胎移植(FET)的两组女性中收集子宫内膜组织样本。RIF 组包括 20 名经历过≥3 次 ETs 的女性,这些 ETs 共包括≥4 个优质胚胎,但均未怀孕,而对照组包括 10 名过去一年至少生育过一次的女性。在着床窗期(LH+7)进行子宫内膜活检。使用扫描电子显微镜(SEM)评估所有组的子宫内膜活检样本中指状突起的发育情况。使用定量逆转录聚合酶链反应和 Western blot 检测 miR-30d-5p、SOCS1 和 LIF 通路的表达水平。

结果

LH+7 时,RIF 患者的指状突起发育减少。RIF 患者着床窗期的 miR-30d-5p 表达水平降低,而 SOCS1 的 mRNA 和蛋白水平在 RIF 组显著高于对照组。此外,miR-30d-5p 的表达与 SOCS1 呈负相关(r=0.8362)。此外,RIF 患者着床窗期 LIF 和 p-STAT3 的表达明显下降。

结论

miR-30d-5p 和 SOCS1 可能是子宫内膜容受性的潜在生物标志物。指状突起发育的变化以及 miR-30d-5p、SOCS1 和 LIF 通路在子宫内膜中的异常表达可能是着床失败的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5c/8425163/2a42ef31d9d4/12958_2021_820_Fig1_HTML.jpg

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