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Rapamycin improves the developmental competence of human oocytes by alleviating DNA damage during IVM

STUDY QUESTION: Can rapamycin improve the developmental competence of human oocytes during the IVM process? SUMMARY ANSWER: Rapamycin at 10 nM could markedly improve the developmental competence of human oocytes undergoing IVM. WHAT IS KNOWN ALREADY: Embryos derived from oocytes that mature in vitro...

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Autores principales: Yang, Qiyu, Xi, Qingsong, Wang, Meng, Liu, Jing, Li, Zhou, Hu, Juan, Jin, Lei, Zhu, Lixia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9731209/
https://www.ncbi.nlm.nih.gov/pubmed/36518986
http://dx.doi.org/10.1093/hropen/hoac050
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author Yang, Qiyu
Xi, Qingsong
Wang, Meng
Liu, Jing
Li, Zhou
Hu, Juan
Jin, Lei
Zhu, Lixia
author_facet Yang, Qiyu
Xi, Qingsong
Wang, Meng
Liu, Jing
Li, Zhou
Hu, Juan
Jin, Lei
Zhu, Lixia
author_sort Yang, Qiyu
collection PubMed
description STUDY QUESTION: Can rapamycin improve the developmental competence of human oocytes during the IVM process? SUMMARY ANSWER: Rapamycin at 10 nM could markedly improve the developmental competence of human oocytes undergoing IVM. WHAT IS KNOWN ALREADY: Embryos derived from oocytes that mature in vitro have lower developmental competence than sibling embryos derived from oocytes matured in vivo. Rapamycin was shown to effectively improve IVM outcomes in mammalian oocytes; however, its effects on IVM of human oocytes have not been investigated. STUDY DESIGN, SIZE, DURATION: In 2021, donated immature oocytes (n = 202) from 80 infertile couples receiving ICSI were included in a control group, and 156 oocytes from 72 couples were included in a rapamycin group. The oocytes underwent IVM with 10 nM rapamycin or without (control) rapamycin, followed by insemination by ICSI and embryo culture. PARTICIPANTS/MATERIALS, SETTING, METHODS: The germinal vesicle breakdown (GVBD), maturation, normal fertilization, high-quality embryo (HQE) and blastocyst formation rates were calculated to evaluate the developmental competence of IVM oocytes, and fluorescence staining was used to assess DNA damage levels of oocytes in both groups. Whole-genome amplification and DNA sequencing were performed to analyze chromosome euploidy in embryos derived from the rapamycin group. MAIN RESULTS AND THE ROLE OF CHANCE: The baseline characteristics of patients who donated oocytes for the two experimental groups were similar. In the control group, GVBD happened in 135 (66.8%) oocytes, and the maturation rate reached 52.5% at 24 h and 63.4% at 48 h. In the rapamycin group, 143 (91.7%) oocytes underwent GVBD, and the maturation rate reached 60.3% at 24 h and 82.7% at 48 h. Following ICSI, more HQEs were obtained in the rapamycin group versus control (34.2% versus 22.1%, respectively, P = 0.040), although with comparable fertilization rates in the two groups. In addition, the levels of histone γH2AX in oocytes cultured with 10 nM rapamycin were markedly decreased, compared with those in the control group (0.3 ± 0.0 versus 0.6 ± 0.1, respectively, P = 0.048). Embryos with normal karyotype could be obtained from oocytes cultured with rapamycin. LIMITATIONS, REASONS FOR CAUTION: Our preliminary results indicated that the addition of rapamycin during human oocyte IVM did not cause extra aneuploidy. However, this safety evaluation of rapamycin treatment was based on limited samples and more data are needed before possible application in the clinic. WIDER IMPLICATIONS OF THE FINDINGS: In the current study, 10 nM rapamycin was applied in the IVM process of human oocytes for the first time and showed positive effects, providing new insights for potentially improving IVM outcomes in the clinic. There were subtle differences between the results presented here on human oocytes and our previous studies on mouse oocytes, indicating the necessity of more research on human samples. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the research grants from National Key Research and Development Project (2018YFC1002103) and Health Commission of Hubei Province scientific research project (WJ2021M110). All authors declared no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
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spelling pubmed-97312092022-12-13 Rapamycin improves the developmental competence of human oocytes by alleviating DNA damage during IVM Yang, Qiyu Xi, Qingsong Wang, Meng Liu, Jing Li, Zhou Hu, Juan Jin, Lei Zhu, Lixia Hum Reprod Open Original Article STUDY QUESTION: Can rapamycin improve the developmental competence of human oocytes during the IVM process? SUMMARY ANSWER: Rapamycin at 10 nM could markedly improve the developmental competence of human oocytes undergoing IVM. WHAT IS KNOWN ALREADY: Embryos derived from oocytes that mature in vitro have lower developmental competence than sibling embryos derived from oocytes matured in vivo. Rapamycin was shown to effectively improve IVM outcomes in mammalian oocytes; however, its effects on IVM of human oocytes have not been investigated. STUDY DESIGN, SIZE, DURATION: In 2021, donated immature oocytes (n = 202) from 80 infertile couples receiving ICSI were included in a control group, and 156 oocytes from 72 couples were included in a rapamycin group. The oocytes underwent IVM with 10 nM rapamycin or without (control) rapamycin, followed by insemination by ICSI and embryo culture. PARTICIPANTS/MATERIALS, SETTING, METHODS: The germinal vesicle breakdown (GVBD), maturation, normal fertilization, high-quality embryo (HQE) and blastocyst formation rates were calculated to evaluate the developmental competence of IVM oocytes, and fluorescence staining was used to assess DNA damage levels of oocytes in both groups. Whole-genome amplification and DNA sequencing were performed to analyze chromosome euploidy in embryos derived from the rapamycin group. MAIN RESULTS AND THE ROLE OF CHANCE: The baseline characteristics of patients who donated oocytes for the two experimental groups were similar. In the control group, GVBD happened in 135 (66.8%) oocytes, and the maturation rate reached 52.5% at 24 h and 63.4% at 48 h. In the rapamycin group, 143 (91.7%) oocytes underwent GVBD, and the maturation rate reached 60.3% at 24 h and 82.7% at 48 h. Following ICSI, more HQEs were obtained in the rapamycin group versus control (34.2% versus 22.1%, respectively, P = 0.040), although with comparable fertilization rates in the two groups. In addition, the levels of histone γH2AX in oocytes cultured with 10 nM rapamycin were markedly decreased, compared with those in the control group (0.3 ± 0.0 versus 0.6 ± 0.1, respectively, P = 0.048). Embryos with normal karyotype could be obtained from oocytes cultured with rapamycin. LIMITATIONS, REASONS FOR CAUTION: Our preliminary results indicated that the addition of rapamycin during human oocyte IVM did not cause extra aneuploidy. However, this safety evaluation of rapamycin treatment was based on limited samples and more data are needed before possible application in the clinic. WIDER IMPLICATIONS OF THE FINDINGS: In the current study, 10 nM rapamycin was applied in the IVM process of human oocytes for the first time and showed positive effects, providing new insights for potentially improving IVM outcomes in the clinic. There were subtle differences between the results presented here on human oocytes and our previous studies on mouse oocytes, indicating the necessity of more research on human samples. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the research grants from National Key Research and Development Project (2018YFC1002103) and Health Commission of Hubei Province scientific research project (WJ2021M110). All authors declared no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A. Oxford University Press 2022-11-11 /pmc/articles/PMC9731209/ /pubmed/36518986 http://dx.doi.org/10.1093/hropen/hoac050 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Article
Yang, Qiyu
Xi, Qingsong
Wang, Meng
Liu, Jing
Li, Zhou
Hu, Juan
Jin, Lei
Zhu, Lixia
Rapamycin improves the developmental competence of human oocytes by alleviating DNA damage during IVM
title Rapamycin improves the developmental competence of human oocytes by alleviating DNA damage during IVM
title_full Rapamycin improves the developmental competence of human oocytes by alleviating DNA damage during IVM
title_fullStr Rapamycin improves the developmental competence of human oocytes by alleviating DNA damage during IVM
title_full_unstemmed Rapamycin improves the developmental competence of human oocytes by alleviating DNA damage during IVM
title_short Rapamycin improves the developmental competence of human oocytes by alleviating DNA damage during IVM
title_sort rapamycin improves the developmental competence of human oocytes by alleviating dna damage during ivm
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9731209/
https://www.ncbi.nlm.nih.gov/pubmed/36518986
http://dx.doi.org/10.1093/hropen/hoac050
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