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Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation

BACKGROUND: Increasing evidence has shown that the mammalian target of rapamycin (mTOR) pathway plays a critical role in oocyte meiosis and embryonic development, however, previous studies reporting the effects of rapamycin on oocyte IVM showed different or even opposite results, and the specific me...

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Autores principales: Yang, Qiyu, Xi, Qingsong, Wang, Meng, Long, Rui, Hu, Juan, Li, Zhou, Ren, Xinling, Zhu, Lixia, Jin, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014618/
https://www.ncbi.nlm.nih.gov/pubmed/35436937
http://dx.doi.org/10.1186/s12958-022-00943-0
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author Yang, Qiyu
Xi, Qingsong
Wang, Meng
Long, Rui
Hu, Juan
Li, Zhou
Ren, Xinling
Zhu, Lixia
Jin, Lei
author_facet Yang, Qiyu
Xi, Qingsong
Wang, Meng
Long, Rui
Hu, Juan
Li, Zhou
Ren, Xinling
Zhu, Lixia
Jin, Lei
author_sort Yang, Qiyu
collection PubMed
description BACKGROUND: Increasing evidence has shown that the mammalian target of rapamycin (mTOR) pathway plays a critical role in oocyte meiosis and embryonic development, however, previous studies reporting the effects of rapamycin on oocyte IVM showed different or even opposite results, and the specific mechanisms were not clear. METHODS: The immature oocytes from female mice underwent IVM with rapamycin at different concentrations to select an optimal dose. The maturation rate, activation rate, subsequent cleavage and blastocyst formation rates, spindle assembly, chromosome alignment, mitochondrial membrane potential (MMP), ROS levels, and DNA damage levels were evaluated and compared in oocytes matured with or without rapamycin. In addition, the expression levels of genes associated with mTORC1 pathway, spindle assembly, antioxidant function, and DNA damage repair (DDR) were also assessed and compared. RESULTS: Rapamycin at 10 nM was selected as an optimal concentration based on the higher maturation and activation rate of IVM oocytes. Following subsequent culture, cleavage and blastocyst formation rates were elevated in activated embryos from the rapamycin group. Additionally, oocytes cultured with 10 nM rapamycin presented decreased ROS levels, reduced chromosome aberration, and attenuated levels of γ-H2AX. No significant effects on the percentages of abnormal spindle were observed. Correspondingly, the expressions of Nrf2, Atm, Atr, and Prkdc in IVM oocytes were markedly increased, following the inhibition of mTORC1 pathway by 10 nM rapamycin. CONCLUSION: Rapamycin at 10 nM could ameliorate the developmental competence and quality of IVM oocytes of mice, mainly by improving the chromosome alignments. The inhibition of mTORC1 pathway, which involved in activating DDR-associated genes may act as a potential mechanism for oocyte quality improvement by rapamycin. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12958-022-00943-0.
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spelling pubmed-90146182022-04-19 Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation Yang, Qiyu Xi, Qingsong Wang, Meng Long, Rui Hu, Juan Li, Zhou Ren, Xinling Zhu, Lixia Jin, Lei Reprod Biol Endocrinol Research BACKGROUND: Increasing evidence has shown that the mammalian target of rapamycin (mTOR) pathway plays a critical role in oocyte meiosis and embryonic development, however, previous studies reporting the effects of rapamycin on oocyte IVM showed different or even opposite results, and the specific mechanisms were not clear. METHODS: The immature oocytes from female mice underwent IVM with rapamycin at different concentrations to select an optimal dose. The maturation rate, activation rate, subsequent cleavage and blastocyst formation rates, spindle assembly, chromosome alignment, mitochondrial membrane potential (MMP), ROS levels, and DNA damage levels were evaluated and compared in oocytes matured with or without rapamycin. In addition, the expression levels of genes associated with mTORC1 pathway, spindle assembly, antioxidant function, and DNA damage repair (DDR) were also assessed and compared. RESULTS: Rapamycin at 10 nM was selected as an optimal concentration based on the higher maturation and activation rate of IVM oocytes. Following subsequent culture, cleavage and blastocyst formation rates were elevated in activated embryos from the rapamycin group. Additionally, oocytes cultured with 10 nM rapamycin presented decreased ROS levels, reduced chromosome aberration, and attenuated levels of γ-H2AX. No significant effects on the percentages of abnormal spindle were observed. Correspondingly, the expressions of Nrf2, Atm, Atr, and Prkdc in IVM oocytes were markedly increased, following the inhibition of mTORC1 pathway by 10 nM rapamycin. CONCLUSION: Rapamycin at 10 nM could ameliorate the developmental competence and quality of IVM oocytes of mice, mainly by improving the chromosome alignments. The inhibition of mTORC1 pathway, which involved in activating DDR-associated genes may act as a potential mechanism for oocyte quality improvement by rapamycin. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12958-022-00943-0. BioMed Central 2022-04-18 /pmc/articles/PMC9014618/ /pubmed/35436937 http://dx.doi.org/10.1186/s12958-022-00943-0 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
Yang, Qiyu
Xi, Qingsong
Wang, Meng
Long, Rui
Hu, Juan
Li, Zhou
Ren, Xinling
Zhu, Lixia
Jin, Lei
Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation
title Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation
title_full Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation
title_fullStr Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation
title_full_unstemmed Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation
title_short Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation
title_sort rapamycin improves the quality and developmental competence of mice oocytes by promoting dna damage repair during in vitro maturation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014618/
https://www.ncbi.nlm.nih.gov/pubmed/35436937
http://dx.doi.org/10.1186/s12958-022-00943-0
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