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. Electronic supplementary material The online version of this article (10.1186/s13048-019-0529-x) contains supplementary material, which is available to authorized users.

Age-related alterations in fertilization-induced Ca2+ oscillations depend on the genetic background of mouse oocytes†

“…It has been shown in oocytes of various mouse strains that maternal aging leads to the formation of mitochondria aggregates and a decrease in the mtDNA copy number and mitochondrial activity [ 43 , 81 , 85–89 ]. Moreover, transcriptomic analyses revealed that the expression of genes involved in oxidative phosphorylation and energy metabolism is often misregulated in oocytes from aged mouse females [ 2 , 3 , 6 ].…”

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

“…Although the mechanisms that cause a decline oocyte quality have not been fully elucidated, it is generally accepted that oxidative stress caused by ROS contributes to age-induced dysfunction of oocyte mitochondria and nuclei. It has also been frequently reported that reduced antioxidative function caused by aging are associated with lower oocyte quality [74,75]. While attempts have been made to prevent the lower function and to improve the impaired quality of oocytes, at present no effective method has been established.…”

Luteal Phase Ovarian Stimulation versus Follicular Phase Ovarian Stimulation results in different Human Cumulus cell genes expression: A pilot study

“…Abnormalities in the mitochondrial complex I subunit leads to structural breakdown and failure to initiate proton transport, thus preventing successful ATP production. Once protons are leaked and fail to propagate to other complexes, they cause imbalance mitochondrial membrane potential and increased oxidative stress, which also induces the production of various inflammatory factors, leading to cellular senescence and cell death 41 . Numerous studies have indicated that mitochondrial dysfunction in oocytes has negative impacts on oocyte maturation, fertilization, embryo development, and pregnancy 42 - 44 .…”