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MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1
BACKGROUND: Preimplantation embryonic lethality is a driver of female infertility. Certain microRNAs (miRNAs) have previously been demonstrated to play important roles in the regulation of embryogenesis. METHODS: Normally developing blastocysts and arrested embryos were collected from patients under...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9743540/ https://www.ncbi.nlm.nih.gov/pubmed/36510317 http://dx.doi.org/10.1186/s12958-022-01044-8 |
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author | Jian, Ou MengXia, Ni Shiyu, Xing QingXia, Meng QinYan, Zou Jie, Ding Wei, Wang Jiaojiao, Wan Hong, Li Yining, Huang |
author_facet | Jian, Ou MengXia, Ni Shiyu, Xing QingXia, Meng QinYan, Zou Jie, Ding Wei, Wang Jiaojiao, Wan Hong, Li Yining, Huang |
author_sort | Jian, Ou |
collection | PubMed |
description | BACKGROUND: Preimplantation embryonic lethality is a driver of female infertility. Certain microRNAs (miRNAs) have previously been demonstrated to play important roles in the regulation of embryogenesis. METHODS: Normally developing blastocysts and arrested embryos were collected from patients undergoing intracytoplasmic sperm injection (ICSI), and the expression of specific miRNAs therein was evaluated by qPCR. The overexpression of target molecule miR-145 in early mice embryos was achieved via oocyte microinjection, enabling the subsequent monitoring of how such overexpression impacted embryonic development. Bioinformatics approaches were utilized to identify putative miR-145 target mRNAs, and luciferase reporter assessments were implemented to confirm the ability of miR-145 to regulate Abca1 in HEK293T cells. The functional relationship between miR-145 and Abca1 in the mice’s embryonic development was then confirmed through rescue assays. RESULTS: Abnormally increased miR-145 expression was observed in patients’ arrested embryos, and the exogenous overexpression of this miRNA significantly suppressed mural blastocyst formation. Mechanistically, miR-145 was found to bind to the 3′-untranslated area of the Abca1 mRNA in HK293T cells, thus suppressing its expression and increasing embryonic cholesterol levels. In line with the importance of these cholesterol levels to embryogenesis, the upregulation of Abca1 was sufficient to rescue the observed change in cholesterol levels and the associated retardation of mice embryonic development that occurred in response to the overexpression of miR-145. CONCLUSION: The regulatory dynamics of the miR-145/Abca1 axis play an important role in shaping normal embryonic development. |
format | Online Article Text |
id | pubmed-9743540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-97435402022-12-13 MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 Jian, Ou MengXia, Ni Shiyu, Xing QingXia, Meng QinYan, Zou Jie, Ding Wei, Wang Jiaojiao, Wan Hong, Li Yining, Huang Reprod Biol Endocrinol Research BACKGROUND: Preimplantation embryonic lethality is a driver of female infertility. Certain microRNAs (miRNAs) have previously been demonstrated to play important roles in the regulation of embryogenesis. METHODS: Normally developing blastocysts and arrested embryos were collected from patients undergoing intracytoplasmic sperm injection (ICSI), and the expression of specific miRNAs therein was evaluated by qPCR. The overexpression of target molecule miR-145 in early mice embryos was achieved via oocyte microinjection, enabling the subsequent monitoring of how such overexpression impacted embryonic development. Bioinformatics approaches were utilized to identify putative miR-145 target mRNAs, and luciferase reporter assessments were implemented to confirm the ability of miR-145 to regulate Abca1 in HEK293T cells. The functional relationship between miR-145 and Abca1 in the mice’s embryonic development was then confirmed through rescue assays. RESULTS: Abnormally increased miR-145 expression was observed in patients’ arrested embryos, and the exogenous overexpression of this miRNA significantly suppressed mural blastocyst formation. Mechanistically, miR-145 was found to bind to the 3′-untranslated area of the Abca1 mRNA in HK293T cells, thus suppressing its expression and increasing embryonic cholesterol levels. In line with the importance of these cholesterol levels to embryogenesis, the upregulation of Abca1 was sufficient to rescue the observed change in cholesterol levels and the associated retardation of mice embryonic development that occurred in response to the overexpression of miR-145. CONCLUSION: The regulatory dynamics of the miR-145/Abca1 axis play an important role in shaping normal embryonic development. BioMed Central 2022-12-12 /pmc/articles/PMC9743540/ /pubmed/36510317 http://dx.doi.org/10.1186/s12958-022-01044-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Jian, Ou MengXia, Ni Shiyu, Xing QingXia, Meng QinYan, Zou Jie, Ding Wei, Wang Jiaojiao, Wan Hong, Li Yining, Huang MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
title | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
title_full | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
title_fullStr | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
title_full_unstemmed | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
title_short | MiR-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting Abca1 |
title_sort | mir-145 is upregulated in the retarded preimplantation embryos and modulates cholesterol levels in mice preimplantation embryos through targeting abca1 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9743540/ https://www.ncbi.nlm.nih.gov/pubmed/36510317 http://dx.doi.org/10.1186/s12958-022-01044-8 |
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