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Answer to Controversy: miR-10a Replacement Approaches Do Not Offer Protection against Chemotherapy-Induced Gonadotoxicity in Mouse Model

It is well known that chemotherapeutic agents may lead to premature ovarian failure and infertility. Therefore, fertility preservation is highly recommended for female cancer survivors. Despite the currently available techniques, new, non-invasive methods need to be developed to protect the ovarian...

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Autores principales: Alexandri, Chrysanthi, Stratopoulou, Christina-Anna, Demeestere, Isabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801898/
https://www.ncbi.nlm.nih.gov/pubmed/31597292
http://dx.doi.org/10.3390/ijms20194958
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author Alexandri, Chrysanthi
Stratopoulou, Christina-Anna
Demeestere, Isabelle
author_facet Alexandri, Chrysanthi
Stratopoulou, Christina-Anna
Demeestere, Isabelle
author_sort Alexandri, Chrysanthi
collection PubMed
description It is well known that chemotherapeutic agents may lead to premature ovarian failure and infertility. Therefore, fertility preservation is highly recommended for female cancer survivors. Despite the currently available techniques, new, non-invasive methods need to be developed to protect the ovarian follicles during oncological treatments. MicroRNAs can be effective tools in this field, as they alter their expression during chemotherapy exposure, and hence they can be useful to minimize the off-target toxicity. Previously, we identified several miRNAs with an important role in newborn mouse ovaries exposed to chemotherapy; among them, the miR-10a was one of the most downregulated miRNAs. Given the controversial role of miR-10a in the ovarian function, we decided to investigate its implication in chemotherapy-induced gonadotoxicity. The downregulated levels of miR-10a were restored by a liposome system conjugated with a mimic miR-10a, and the overexpressed miR-10a prevented the upregulation of the targeted gene, phosphatase and tensin homolog (Pten). The apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) Assay and Bax expression quantification, while histological studies were also performed to evaluate the follicle count and development. Our results showed that the miR-10a replacement could not protect the ovaries from chemotherapy-induced apoptosis, whereas the targeting of Pten may affect the follicle activation via the phosphoinositide 3-kinase (PI3K)/PTEN/protein kinase B (AKT) pathway. Consequently, the application of miR-10a in fertility preservation is not recommended, and the role of miR-10a needs to be further elucidated.
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spelling pubmed-68018982019-10-31 Answer to Controversy: miR-10a Replacement Approaches Do Not Offer Protection against Chemotherapy-Induced Gonadotoxicity in Mouse Model Alexandri, Chrysanthi Stratopoulou, Christina-Anna Demeestere, Isabelle Int J Mol Sci Article It is well known that chemotherapeutic agents may lead to premature ovarian failure and infertility. Therefore, fertility preservation is highly recommended for female cancer survivors. Despite the currently available techniques, new, non-invasive methods need to be developed to protect the ovarian follicles during oncological treatments. MicroRNAs can be effective tools in this field, as they alter their expression during chemotherapy exposure, and hence they can be useful to minimize the off-target toxicity. Previously, we identified several miRNAs with an important role in newborn mouse ovaries exposed to chemotherapy; among them, the miR-10a was one of the most downregulated miRNAs. Given the controversial role of miR-10a in the ovarian function, we decided to investigate its implication in chemotherapy-induced gonadotoxicity. The downregulated levels of miR-10a were restored by a liposome system conjugated with a mimic miR-10a, and the overexpressed miR-10a prevented the upregulation of the targeted gene, phosphatase and tensin homolog (Pten). The apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) Assay and Bax expression quantification, while histological studies were also performed to evaluate the follicle count and development. Our results showed that the miR-10a replacement could not protect the ovaries from chemotherapy-induced apoptosis, whereas the targeting of Pten may affect the follicle activation via the phosphoinositide 3-kinase (PI3K)/PTEN/protein kinase B (AKT) pathway. Consequently, the application of miR-10a in fertility preservation is not recommended, and the role of miR-10a needs to be further elucidated. MDPI 2019-10-08 /pmc/articles/PMC6801898/ /pubmed/31597292 http://dx.doi.org/10.3390/ijms20194958 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alexandri, Chrysanthi
Stratopoulou, Christina-Anna
Demeestere, Isabelle
Answer to Controversy: miR-10a Replacement Approaches Do Not Offer Protection against Chemotherapy-Induced Gonadotoxicity in Mouse Model
title Answer to Controversy: miR-10a Replacement Approaches Do Not Offer Protection against Chemotherapy-Induced Gonadotoxicity in Mouse Model
title_full Answer to Controversy: miR-10a Replacement Approaches Do Not Offer Protection against Chemotherapy-Induced Gonadotoxicity in Mouse Model
title_fullStr Answer to Controversy: miR-10a Replacement Approaches Do Not Offer Protection against Chemotherapy-Induced Gonadotoxicity in Mouse Model
title_full_unstemmed Answer to Controversy: miR-10a Replacement Approaches Do Not Offer Protection against Chemotherapy-Induced Gonadotoxicity in Mouse Model
title_short Answer to Controversy: miR-10a Replacement Approaches Do Not Offer Protection against Chemotherapy-Induced Gonadotoxicity in Mouse Model
title_sort answer to controversy: mir-10a replacement approaches do not offer protection against chemotherapy-induced gonadotoxicity in mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801898/
https://www.ncbi.nlm.nih.gov/pubmed/31597292
http://dx.doi.org/10.3390/ijms20194958
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