Dataset Information

Mitochondrial dysfunction and endoplasmic reticulum stress involved in oocyte aging: an analysis using single-cell RNA-sequencing of mouse oocytes.

ABSTRACT:

Object

To explore the mechanisms of ovarian aging, we performed overall analysis on the age-related alterations of gene expression profiles in mouse germinal vesicle (GV) stage oocytes by means of single-cell RNA-sequencing method (scRNA-seq).

Methods

Two age groups (5-week-old and 32-week-old) female KM mice were used as young and old models. Subsequently, GV oocytes were collected for scRNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between GV oocytes of young and old mice.

Results

The analysis of scRNA-seq data showed that there were 624 differential expressed genes (DEGs) between two age groups of mouse GV stage oocytes. Four hundred forty-nine DEGs were up-regulated while 175 DEGs were down-regulated in the GV oocytes of the old group. KEGG pathway analysis revealed that the genes involved in mitochondrial function including oxidative phosphorylation and ATP production pathway were significantly down-regulated in GV oocytes of 32-week-old mice, especially the mitochondrial encoded NADH dehydrogenase (mt-Nd), including mt-Nd2, mt-Nd3, mt-Nd4, mt-Nd4L and mt-Nd5. Analysis of DEGs revealed that endoplasmic reticulum stress-related genes including AdipoR2, IRAK-1, RCAN1 and MsrB1 were significantly down-regulated in GV oocytes of 32-week-old mice. Also, analysis of DEGs demonstrated that anti-oxidation-related genes including Erbb3?Rcan1?Gsto2 and Msrb1 were significantly down-regulated in GV oocytes of old group.

Conclusion

The disorder of mitochondrial function, endoplasmic reticulum stress and the reduced antioxidant capability might be involved in the progression of oocyte aging. Especially, the down regulation of mitochondrial encoded subunits of respiratory chain complexes might play critical roles in the relevant mechanisms.

SUBMITTER: Zhang T

PROVIDER: S-EPMC6556043 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mitochondrial dysfunction and endoplasmic reticulum stress involved in oocyte aging: an analysis using single-cell RNA-sequencing of mouse oocytes.

Zhang Tao T Xi Qingsong Q Wang Dan D Li Jingjing J Wang Meng M Li Dan D Zhu Lixia L Jin Lei L

Journal of ovarian research 20190608 1

<h4>Object</h4>To explore the mechanisms of ovarian aging, we performed overall analysis on the age-related alterations of gene expression profiles in mouse germinal vesicle (GV) stage oocytes by means of single-cell RNA-sequencing method (scRNA-seq).<h4>Methods</h4>Two age groups (5-week-old and 32-week-old) female KM mice were used as young and old models. Subsequently, GV oocytes were collected for scRNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expr ...[more]

PMID: 31176373

Similar Datasets

Project description:Ca(2+) oscillations are a hallmark of mammalian fertilization and play a central role in the activation of development. The calcium required for these oscillations is primarily derived from the endoplasmic reticulum (ER), which accumulates in clusters at the microvillar subcortex during oocyte maturation. The migration of the ER to the cortex during maturation is thought to play an important role in rendering the ER competent to generate the calcium transients, and the redistribution of ER is believed to be primarily mediated by microtubules and microfilaments. We have previously shown that the oocyte- and early embryo-restricted maternal effect gene Mater (Nlrp5) localizes to, and is required for, formation of the oocyte cytoplasmic lattices, a tubulin-containing structure that appears to play an important role in organelle positioning and distribution during oocyte maturation. Given these observations, we hypothesized that Mater may also be required for ER redistribution and Ca(2+) homeostasis in oocytes. To test this hypothesis, we first investigated ER localization in metaphase-II Mater(tm/tm) (hypomorph) oocytes and found ER clusters to be less abundant at the microvillar cortex when compared to wild type oocytes. To examine the potential mechanisms by which MATER mediates ER redistribution, we tested whether tubulin expression levels and localization were affected in the mutant oocytes and found that the Triton-insoluble fraction of tubulin was significantly decreased in Mater(tm/tm) oocytes. To identify potential functional defects associated with these ER abnormalities, we next set out to investigate if the pattern of Ca(2+) oscillations was altered in Mater(tm/tm) oocytes after fertilization in vitro. Intriguingly, Ca(2+) oscillations in Mater(tm/tm) oocytes exhibited a significantly lower first peak amplitude and a higher frequency when compared to wild type oocytes. We then found that the Ca(2+) oscillation defect in Mater(tm/tm) oocytes was likely caused by a reduced amount of Ca(2+) in the ER stores. Taken together, these observations support the hypothesis that MATER is required for ER distribution and Ca(2+) homeostasis in oocytes, likely due to defects in lattice-mediated ER positioning and/or redistribution.

Project description:The oocytes presenting SERa are considered dysmorphic and have been associated with reduced embryological outcome and an increased risk of congenital anomalies. Therefore, in 2011 the Alpha/ESHRE Consensus strongly recommended not to inseminate MII oocytes displaying SERa (SERa+). Not all Centers follow this recommendation and some Authors reported that SERa+ can lead to healthy newborns. Moreover, no experimental data about the effect of SERa presence on the oocyte molecular status are available. To date the question whether or not SERa+ oocytes should be discarded as well as the opportunity to review or not the ESHRE consensus are still open for debate. This study included 28 women, < 38 years aged, without any ovarian pathology, undergoing IVF treatment. Supernumerary MII oocytes with no sign of morphological alterations and SERa+ oocytes were donated after written informed consent. A total of 31 oocytes without SERa (SERa-) and 24 SERa+ oocytes were analyzed. Pools of ≈10 oocytes for both group were prepared. Total RNA was extracted from each pool, amplified, labelled and hybridized on oligonucleotide microarrays. Analyses were performed by R software using the limma package. The expression profiles of SERa+ oocytes significantly differed from those of SERa- oocytes in 488 probe sets corresponding to 102 down-regulated and 283 up-regulated unique transcripts. Gene Ontology analysis by DAVID bioinformatics resource disclosed that three main biological processes were significantly down-regulated in SERa+ oocytes respect to SERa- oocytes: i) genes involved in cell and mitotic nuclear division, spindle assembly, chromosome partition and G2/M transition of mitotic cell cycle; ii) organization of cytoskeleton and microtubules; iii) mitochondrial structure and activity. Among the transcripts up-regulated in SERa+ oocytes, the most significantly (P= 0.002) enriched GO term was “GoLoco motif” including RAP1GAP, GPSM3, and GPSM1 genes. Data validation in a larger cohort of samples would be beneficial, although we applied stringent criteria for gene selection (fold-change >3 or <1/3 and FDR<0.1). Surveys on clinical outcomes, malformation rates, and follow-up of babies born after transfer of embryos from SERa+ oocytes are necessary. For the first time we provide information on molecular status of SERa+ oocytes, highlighting possible correlations among presence of SERa, altered oocyte physiology and reduced developmental competence. Based on our findings, we believe that it is far too early for an eventual revision of the 2011 Alpha/ESHRE Consensus on the issue and presence of SERa should be still a “red flag” in clinical IVF practices.

Dataset Information

Mitochondrial dysfunction and endoplasmic reticulum stress involved in oocyte aging: an analysis using single-cell RNA-sequencing of mouse oocytes.

Object

Methods

Results

Conclusion

Publications

Mitochondrial dysfunction and endoplasmic reticulum stress involved in oocyte aging: an analysis using single-cell RNA-sequencing of mouse oocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets