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...

Full description

Bibliographic Details
Main Authors: Hao Qin, Yi Qu, Rong Li, Jie Qiao
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2022.816606/full
_version_ 1818954574687371264
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.
first_indexed 2024-12-20T10:24:20Z
format Article
id doaj.art-5756c83c087d422cb32882d59f2cee28
institution Directory Open Access Journal
issn 1664-2392
language English
last_indexed 2024-12-20T10:24:20Z
publishDate 2022-01-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Endocrinology
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
work_keys_str_mv AT haoqin invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT haoqin invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT haoqin invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT haoqin invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT yiqu invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT yiqu invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT yiqu invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT yiqu invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT rongli invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT rongli invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT rongli invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT rongli invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT jieqiao invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT jieqiao invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT jieqiao invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT jieqiao invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation
AT jieqiao invivoandinvitromaturedoocytesfrommiceofadvancedreproductiveageexhibitalternativesplicingprocessesformitochondrialoxidativephosphorylation