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Series GSE147547 Query DataSets for GSE147547
Status Public on Dec 31, 2020
Title Post-implantation developmental defects induced by mtDNA mutation derive from altered DNA methylome in oocytes
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary Accumulating evidences suggest a link between mitochondrial dysfunction and female reproduction decline. To directly and systematically figure out the influence of mitochondrial DNA (mtDNA) mutation on oocyte quality and embryo development, we used an mtDNA mutator mouse model (D257A) that harbors a proofreading-deficient version of PolgA. Here we showed that D257A mice developed a profound reduction of fertility at 19-week of age, and accumulated twofold more increase in the levels of point mutations in oocyte mtDNA. Following ovarian hyper-stimulation, we found oocyte numbers retrieved from WT and D257A mice were comparable until 19 weeks of age, while with a half reduced number of oocyte ovulated in D257A mice thereafter. We further found the oocyte quality based on mitochondrial distribution, meiotic spindle assembly, chromosomal segregation and ATP content at 19 weeks of age was identical in both group. Meanwhile, the ovulated oocytes can initiate and sustain early embryo development after in vitro fertilization, and reach the blastocyst stage with no obvious defects compared to WTs. Of note, post-implantation developmental defects were observed in D257A embryos, as revealed by fetal growth retardation and decreased ratios of pups delivered. Furthermore, genome-wide methylation analysis revealed global hypomethylation across the genome of D257A oocytes, with a dramatic reduce in genome repetitive-elements, like DNA transposon, LINEs and SINEs regions. In conclusion, our study presents the direct experimental investigation of the effect of mtDNA mutation on oocyte and embryo competence, and demonstrates altered DNA methylation in oocyte may represent a critical mechanism that mediates the phenotypic defects of mtDNA mutation in post-implantation development.
Overall design Two groups with three replicates were used.
Contributor(s) Han L
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Submission date Mar 25, 2020
Last update date Jan 02, 2021
Contact name Wenjie Shu
Organization name Beijing Institute of Radiation Medicine
Street address Taiping Road 27
City Beijing
ZIP/Postal code 100850
Country China
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (6)
GSM4433065 D257A ooycte rep1
GSM4433066 D257A ooycte rep2
GSM4433067 D257A ooycte rep3
BioProject PRJNA615227
SRA SRP254051

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GSE147547_RAW.tar 648.4 Mb (http)(custom) TAR (of BEDGRAPH)
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Raw data are available in SRA
Processed data provided as supplementary file

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