Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells
Background In vitro fertilization-embryo transfer (IVF-ET) is a crucial assisted reproductive technology for treating infertility. However, recurrent implantation failure (RIF), a significant challenge in IVF-ET success, remains unresolved. This study aimed to explore the role and mechanism of FLI1...
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PeerJ Inc.
2023-09-01
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author | Yile Zhang Beining Yin Sichen Li Yueyue Cui Jianrong Liu |
author_facet | Yile Zhang Beining Yin Sichen Li Yueyue Cui Jianrong Liu |
author_sort | Yile Zhang |
collection | DOAJ |
description | Background In vitro fertilization-embryo transfer (IVF-ET) is a crucial assisted reproductive technology for treating infertility. However, recurrent implantation failure (RIF), a significant challenge in IVF-ET success, remains unresolved. This study aimed to explore the role and mechanism of FLI1 in endometrial receptivity and RIF. Methods Differential endometrial cell proportions between patients with RIF and control subjects were assessed using single-cell RNA sequencing (scRNA-seq) analysis. The chromatin accessibility of FLI1 in the luteal endometrial tissue of patients with RIF and control subjects was examined using the single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq). FLI1 mRNA and protein levels were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Cell viability and migration were examined via cell counting kit (CCK)-8 and scratch healing assays. Epithelial-mesenchymal transition markers were analyzed using western blotting. Mechanisms underlying FLI1’s regulation of PART1 transcription and expression in endometrial epithelial cells were explored using chromatin immunoprecipitation and dual-luciferase reporter assays. Adeno-associated virus (AAV) carrying epithelial cell-specific FLI1/PART1 overexpression sequences was uterinely injected in mice to assess FLI1/PART1 effects. Results scRNA-seq revealed diminished endometrial epithelial cell proportions in RIF patients. Meanwhile, scATAC-seq indicated enhanced chromatin accessibility of FLI1 in these cells. FLI1 exhibited specific expression in RIF patients’ endometrial epithelial cells. Specific FLI1 overexpression inhibited embryo implantation, while knockdown enhanced it. Pregnant mice injected with AAV encoding FLI1 overexpression had significantly lower implantation than AAV-negative controls. FLI1 binding to PART1 promoter heightened PART1 transcription and expression in endometrial epithelial cells. Rescue experiments illustrated FLI1’s role in embryo implantation by boosting PART1 expression. PART1 was notably elevated in RIF patients’ luteal endometrial tissue and non-receptive endometrial epithelial cells (HEC-1-A). Specific PART1 overexpression dampened embryo implantation, whereas knockdown promoted it. Pregnant mice injected with AAV encoding PART1 had lower implantation than negative controls. PART1 knockdown mitigated FLI1’s inhibitory impact on HEC-1-A cell viability and migration. Conclusions FLI1 overexpression in the endometrial epithelial cells of patients with RIF inhibited embryo implantation by binding to the PART1 promoter region to promote PART1 expression. These findings can aid in the development of novel therapeutic targets for RIF. |
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spelling | doaj.art-1a5a7b824dc54d3ebc275325aa0a6b442023-12-03T09:43:41ZengPeerJ Inc.PeerJ2167-83592023-09-0111e1610510.7717/peerj.16105Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cellsYile Zhang0Beining Yin1Sichen Li2Yueyue Cui3Jianrong Liu4Reproductive Medical Center, The Fifth Clinical Medical College of Shanxi Medical University, Shanxi Provincial People’s hospital, Taiyuan, ChinaReproductive Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaReproductive Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaReproductive Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaReproductive Medical Center, The Fifth Clinical Medical College of Shanxi Medical University, Shanxi Provincial People’s hospital, Taiyuan, ChinaBackground In vitro fertilization-embryo transfer (IVF-ET) is a crucial assisted reproductive technology for treating infertility. However, recurrent implantation failure (RIF), a significant challenge in IVF-ET success, remains unresolved. This study aimed to explore the role and mechanism of FLI1 in endometrial receptivity and RIF. Methods Differential endometrial cell proportions between patients with RIF and control subjects were assessed using single-cell RNA sequencing (scRNA-seq) analysis. The chromatin accessibility of FLI1 in the luteal endometrial tissue of patients with RIF and control subjects was examined using the single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq). FLI1 mRNA and protein levels were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Cell viability and migration were examined via cell counting kit (CCK)-8 and scratch healing assays. Epithelial-mesenchymal transition markers were analyzed using western blotting. Mechanisms underlying FLI1’s regulation of PART1 transcription and expression in endometrial epithelial cells were explored using chromatin immunoprecipitation and dual-luciferase reporter assays. Adeno-associated virus (AAV) carrying epithelial cell-specific FLI1/PART1 overexpression sequences was uterinely injected in mice to assess FLI1/PART1 effects. Results scRNA-seq revealed diminished endometrial epithelial cell proportions in RIF patients. Meanwhile, scATAC-seq indicated enhanced chromatin accessibility of FLI1 in these cells. FLI1 exhibited specific expression in RIF patients’ endometrial epithelial cells. Specific FLI1 overexpression inhibited embryo implantation, while knockdown enhanced it. Pregnant mice injected with AAV encoding FLI1 overexpression had significantly lower implantation than AAV-negative controls. FLI1 binding to PART1 promoter heightened PART1 transcription and expression in endometrial epithelial cells. Rescue experiments illustrated FLI1’s role in embryo implantation by boosting PART1 expression. PART1 was notably elevated in RIF patients’ luteal endometrial tissue and non-receptive endometrial epithelial cells (HEC-1-A). Specific PART1 overexpression dampened embryo implantation, whereas knockdown promoted it. Pregnant mice injected with AAV encoding PART1 had lower implantation than negative controls. PART1 knockdown mitigated FLI1’s inhibitory impact on HEC-1-A cell viability and migration. Conclusions FLI1 overexpression in the endometrial epithelial cells of patients with RIF inhibited embryo implantation by binding to the PART1 promoter region to promote PART1 expression. These findings can aid in the development of novel therapeutic targets for RIF.https://peerj.com/articles/16105.pdfRecurrent implantation failure (RIF)Single cell chromatin accessibility sequencing (scATAC-seq)FLI1PART1Endometrial receptivity |
spellingShingle | Yile Zhang Beining Yin Sichen Li Yueyue Cui Jianrong Liu Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells PeerJ Recurrent implantation failure (RIF) Single cell chromatin accessibility sequencing (scATAC-seq) FLI1 PART1 Endometrial receptivity |
title | Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells |
title_full | Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells |
title_fullStr | Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells |
title_full_unstemmed | Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells |
title_short | Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells |
title_sort | friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting part1 transcription in the endometrial epithelial cells |
topic | Recurrent implantation failure (RIF) Single cell chromatin accessibility sequencing (scATAC-seq) FLI1 PART1 Endometrial receptivity |
url | https://peerj.com/articles/16105.pdf |
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