In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative Phosphorylation
The mean age of women seeking infertility treatment has gradually increased over recent years. This has coincided with the emergence of in vitro maturation (IVM), a method used in assisted reproductive technology for patients with special requirements. However, when compared with conventional in vit...
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Frontiers Media S.A.
2022-01-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.816606/full |
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author | Hao Qin Hao Qin Hao Qin Hao Qin Yi Qu Yi Qu Yi Qu Yi Qu Rong Li Rong Li Rong Li Rong Li Jie Qiao Jie Qiao Jie Qiao Jie Qiao Jie Qiao |
author_facet | Hao Qin Hao Qin Hao Qin Hao Qin Yi Qu Yi Qu Yi Qu Yi Qu Rong Li Rong Li Rong Li Rong Li Jie Qiao Jie Qiao Jie Qiao Jie Qiao Jie Qiao |
author_sort | Hao Qin |
collection | DOAJ |
description | The mean age of women seeking infertility treatment has gradually increased over recent years. This has coincided with the emergence of in vitro maturation (IVM), a method used in assisted reproductive technology for patients with special requirements. However, when compared with conventional in vitro fertilization, IVM is associated with poor embryonic development potential and low live birth rates, thus limiting the widespread application of this technique. In this study, we performed RNA-sequencing transcriptomic assays and identified a total of 2,627 significant differentially expressed genes (DEGs) between IVM oocytes and in vivo matured oocytes from mice of advanced reproductive age. Next, Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to identify the potential functions of the DEGs. The most significantly enriched pathway was oxidative phosphorylation (OXPHOS). In addition, we constructed a protein-protein interaction network to identify key genes and determined that most of the hub genes were mtDNA-encoded subunits of respiratory chain complex I. Antioxidant supplementation lead to an increase in ATP production and reduced the gene expression profile of the OXPHOS pathway in the IVM group. Moreover, alternative splicing (AS) events were identified during in vivo or in vitro oocyte maturation; data showed that skipped exons were the most frequent type of AS event. A number of genes associated with the OXPHOS pathway exhibited alterations in AS events, including Ndufa7, Ndufs7, Cox6a2, Ndufs5, Ndufb1, and Uqcrh. Furthermore, the process of IVO promoted the skipping of exon 2 in Ndufa7 and exon 3 in Ndufs7 compared with the IVM oocytes, as determined by semi−quantitative RT−PCR. Collectively, these findings provide potential new therapeutic targets for improving IVM of aged women who undergo infertility treatment. |
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language | English |
last_indexed | 2024-12-20T10:24:20Z |
publishDate | 2022-01-01 |
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spelling | doaj.art-5756c83c087d422cb32882d59f2cee282022-12-21T19:43:51ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-01-011310.3389/fendo.2022.816606816606In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative PhosphorylationHao Qin0Hao Qin1Hao Qin2Hao Qin3Yi Qu4Yi Qu5Yi Qu6Yi Qu7Rong Li8Rong Li9Rong Li10Rong Li11Jie Qiao12Jie Qiao13Jie Qiao14Jie Qiao15Jie Qiao16Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaKey Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaKey Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaKey Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaKey Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, ChinaResearch Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, ChinaThe mean age of women seeking infertility treatment has gradually increased over recent years. This has coincided with the emergence of in vitro maturation (IVM), a method used in assisted reproductive technology for patients with special requirements. However, when compared with conventional in vitro fertilization, IVM is associated with poor embryonic development potential and low live birth rates, thus limiting the widespread application of this technique. In this study, we performed RNA-sequencing transcriptomic assays and identified a total of 2,627 significant differentially expressed genes (DEGs) between IVM oocytes and in vivo matured oocytes from mice of advanced reproductive age. Next, Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to identify the potential functions of the DEGs. The most significantly enriched pathway was oxidative phosphorylation (OXPHOS). In addition, we constructed a protein-protein interaction network to identify key genes and determined that most of the hub genes were mtDNA-encoded subunits of respiratory chain complex I. Antioxidant supplementation lead to an increase in ATP production and reduced the gene expression profile of the OXPHOS pathway in the IVM group. Moreover, alternative splicing (AS) events were identified during in vivo or in vitro oocyte maturation; data showed that skipped exons were the most frequent type of AS event. A number of genes associated with the OXPHOS pathway exhibited alterations in AS events, including Ndufa7, Ndufs7, Cox6a2, Ndufs5, Ndufb1, and Uqcrh. Furthermore, the process of IVO promoted the skipping of exon 2 in Ndufa7 and exon 3 in Ndufs7 compared with the IVM oocytes, as determined by semi−quantitative RT−PCR. Collectively, these findings provide potential new therapeutic targets for improving IVM of aged women who undergo infertility treatment.https://www.frontiersin.org/articles/10.3389/fendo.2022.816606/fulloocytein vitro maturationoxidative phosphorylationtranscriptomedifferentially expressed genesalternative splicing |
spellingShingle | Hao Qin Hao Qin Hao Qin Hao Qin Yi Qu Yi Qu Yi Qu Yi Qu Rong Li Rong Li Rong Li Rong Li Jie Qiao Jie Qiao Jie Qiao Jie Qiao Jie Qiao In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative Phosphorylation Frontiers in Endocrinology oocyte in vitro maturation oxidative phosphorylation transcriptome differentially expressed genes alternative splicing |
title | In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative Phosphorylation |
title_full | In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative Phosphorylation |
title_fullStr | In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative Phosphorylation |
title_full_unstemmed | In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative Phosphorylation |
title_short | In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative Phosphorylation |
title_sort | in vivo and in vitro matured oocytes from mice of advanced reproductive age exhibit alternative splicing processes for mitochondrial oxidative phosphorylation |
topic | oocyte in vitro maturation oxidative phosphorylation transcriptome differentially expressed genes alternative splicing |
url | https://www.frontiersin.org/articles/10.3389/fendo.2022.816606/full |
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