Dataset Information

Association of miRNA-145 with the occurrence and prognosis of hydrosalpinx-induced defective endometrial receptivity.

ABSTRACT: MiR-145 is reported to facilitate inflammation and is also associated with unsuccessful embryonic implantation. Whether miR-145 mediates inflammatory response underlying hydrosalpinx-induced defective endometrial receptivity (ER) remains unclear, and this study attempted to clarify this point. Endometrium samples were collected from hydrosalpinx patients (case, n = 243) and patients with tubal patency/obstruction (control, n = 187). The peripheral blood samples of cases and controls were collected to determine the genotypes of miR-145 SNPs. The value of miR-145 expression in the diagnosis and prognostic estimation of hydrosalpinx was assessed using ROC curve and regression analysis, respectively. Lipopolysaccharide (LPS) cell model was established with endometrial cells, and cells were transfected with miR-145 mimic, inhibitor, or negative control. MiR-145 and cytokine levels were quantified by quantitative reverse transcription PCR or western blot. MiR-145 expression was significantly higher in hydrosalpinx compared to control group, and high miR-145 expression was significantly associated with moderate/severe tube lesion, high pulsatility index (>1.06), and high resistance index (>0.61) in hydrosalpinx patients. ROC curve analysis indicated that monitoring miR-145 expression may be useful for the diagnosis of hydrosalpinx (AUC = 0.704). A alleles of rs41291957 (G>A) and rs353292 (G>A) were significantly associated with an increased risk of hydrosalpinx compared to G allele (p < 0.05), yet the mutant allele of rs353291 (A>G) and rs4705343 (T>C) significantly reduced susceptibility to hydrosalpinx compared to the wild type allele. Treatments with miR-145 mimic and LPS in endometrial cells significantly increased the levels of transforming growth factor-?1, tumor necrosis factor -?, interleukin (IL)-6, and IL-8 compared to negative control, while treatment with miR-145 inhibitor decreased the cytokine levels. In conclusion, abnormally expressed miR-145 may be involved in hydrosalpinx-induced ER defects by regulating the inflammatory response.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7861628 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Association of miRNA-145 with the occurrence and prognosis of hydrosalpinx-induced defective endometrial receptivity.

Wang Qingli Q Ai Haiquan H Li Xia X Tian Haiqing H Ning Bingxue B Zhang Meng M La Xiaolin X

Bosnian journal of basic medical sciences 20210201 1

MiR-145 is reported to facilitate inflammation and is also associated with unsuccessful embryonic implantation. Whether miR-145 mediates inflammatory response underlying hydrosalpinx-induced defective endometrial receptivity (ER) remains unclear, and this study attempted to clarify this point. Endometrium samples were collected from hydrosalpinx patients (case, n = 243) and patients with tubal patency/obstruction (control, n = 187). The peripheral blood samples of cases and controls were collect ...[more]

PMID: 32343942

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Project description:BackgroundA receptive endometrium is a prerequisite for successful embryo implantation. Mounting evidence shows that nearly one-third of infertility and implantation failures are caused by defective endometrial receptivity. This study pooled 218 subjects from multiple datasets to investigate the association of the immune infiltration level with reproductive outcome. Additionally, macrophage-endometrium interaction modules were constructed to explore an accurate and cost-effective approach to endometrial receptivity assessment.MethodsImmune-infiltration levels in 4 GEO datasets (n=218) were analyzed and validated through meta-analysis. Macrophage-endometrium interaction modules were selected based on the weighted gene co-expression network in GSE58144 and differentially expressed genes dominated by GSE19834 dataset. Xgboost, random forests, and regression algorithms were applied to predictive models. Subsequently, the efficacy of the models was compared and validated in the GSE165004 dataset. Forty clinical samples (RT-PCR and western blot) were performed for expression and model validation, and the results were compared to those of endometrial thickness in clinical pregnancy assessment.ResultsAltered levels of Mϕs infiltration were shown to critically influence embryo implantation. The three selected modules, manifested as macrophage-endometrium interactions, were enrichment in the immunoreactivity, decidualization, and signaling functions and pathways. Moreover, hub genes within the modules exerted significant reproductive prognostic effects. The xgboost algorithm showed the best performance among the machine learning models, with AUCs of 0.998 (95% CI 0.994-1) and 0.993 (95% CI 0.979-1) in GSE58144 and GSE165004 datasets, respectively. These results were significantly superior to those of the other two models (random forest and regression). Similarly, the model was significantly superior to ultrasonography (endometrial thickness) with a better cost-benefit ratio in the population.ConclusionSuccessful embryo implantation is associated with infiltration levels of Mϕs, manifested in genetic modules involved in macrophage-endometrium interactions. Therefore, utilizing the hub genes in these modules can provide a platform for establishing excellent machine learning models to predict reproductive outcomes in patients with defective endometrial receptivity.

Project description:STUDY QUESTION:Does intentional endometrial injury (i.e. endometrial scratching) during ART enhance pregnancy rates? SUMMARY ANSWER:We propose a randomized controlled clinical trial in women performing ART in which the intervention group will undergo an additional endometrial biopsy during exogenous ovarian stimulation. WHAT IS KNOWN ALREADY:Although endometrial receptivity has been extensively studied, the mechanisms behind the implantation of an embryo remain largely a mystery. Intentional endometrial injury has been put forward by many researchers as an inexpensive clinical tool capable of enhancing endometrial receptivity. However, despite its widespread use, the benefit of endometrial scratching is still a contentious and unresolved issue. STUDY DESIGN SIZE DURATION:Pragmatic two-arm randomized, single-centre, controlled open-label trial in women undergoing exogenous gonadotropin ovarian stimulation for ART followed by a fresh embryo transfer in a gonadotropin-releasing hormone antagonist suppressed cycle. The trial will include 360 women in total with a 1:1 allocation ratio and an expected total duration of up to 45 months. PARTICIPANTS/MATERIALS SETTING METHODS:Subjects in the intervention group will undergo an endometrial biopsy during the follicular phase, on the sixth to eighth day of exogenous stimulation. Furthermore, nested within this clinical trial, we will also evaluate whether the transcriptomic signatures of the material collected during the biopsy may accurately distinguish women who become pregnant from those who do not. These endometrial transcriptomic signatures will be assessed both immediately after the biopsy and following in-vitro decidualization. MAIN RESULTS AND THE ROLE OF CHANCE:Our primary objective is to assess the effect of endometrial injury during exogenous gonadotropin ovarian stimulation on clinical pregnancy rates after ART. Secondary efficacy and safety outcomes include: live-birth delivery after 24 weeks, the endometrial transcriptomic profile among women in the intervention group, short-term safety (e.g. procedure intolerance due to pain, post-procedure bleeding) and long-term safety (e.g. cancelled transfers, miscarriage) outcomes. LIMITATIONS REASONS FOR CAUTION:Owing to its pragmatic design, this study may have limited power to determine one or more of our secondary outcomes and whether there are specific subgroups of women who may benefit significantly from performing endometrial scratching and endometrial transcriptomic profiling. WIDER IMPLICATIONS OF THE FINDINGS:Despite the weak biological plausibility, heterogeneity in the existing randomized controlled trials and lack of evaluation of any potential risks associated with endometrial scratching, this procedure is still widely applied in current clinical practice. This clinical trial aims to pragmatically assess the potential benefits and harms of the generalized use of this strategy. STUDY FUNDING/COMPETING INTERESTS:this study has received a grant from the Research Foundation-Flanders (FWO, 1524417N). This organization has no further role in the study, namely with regards to protocol development, study conduction and evaluation of results. TRIAL REGISTRATION NUMBER:NCT02061228. TRIAL REGISTRATION DATE:10 February 2014. DATE OF FIRST PATIENT’S ENROLMENT:3 April 2014. PROTOCOL VERSION:2.0.

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Dataset Information

Association of miRNA-145 with the occurrence and prognosis of hydrosalpinx-induced defective endometrial receptivity.

Publications

Association of miRNA-145 with the occurrence and prognosis of hydrosalpinx-induced defective endometrial receptivity.

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