Single cell transcriptome analysis of human oocyte aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE155179 | GEO | 2021/05/27
REPOSITORIES: GEO
Similar Datasets
Project description:A decrease in oocyte developmental potential is a major obstacle for successful pregnancy in women of advanced age. However, the age-related epigenetic modifications associated with dynamic transcriptome changes, particularly meiotic maturation-coupled mRNA clearance, have not been adequately characterized in human oocytes. This study demonstrate a decreased storage of transcripts encoding key factors regulating the maternal mRNA degradome in fully grown oocytes of women of advanced age. A similar defect in meiotic maturation-triggered mRNA clearance was also detected in aged mouse oocytes. Mechanistically, the epigenetic and cytoplasmic aspects of oocyte maturation are synchronized in both the normal development and aging processes. The level of histone H3K4 trimethylation (H3K4me3) was high in fully grown mouse and human oocytes derived from young females but decreased during aging due to the decreased expression of epigenetic factors responsible for H3K4me3 accumulation. Oocyte-specific knockout of the gene encoding CxxC-finger protein 1 (CXXC1), a DNA-binding subunit of SETD1 methyltransferase, caused ooplasm changes associated with accelerated aging and impaired maternal mRNA translation and degradation. These results suggest that a network of CXXC1-maintained H3K4me3, in association with mRNA decay competence, sets a timer for oocyte deterioration and plays a role in oocyte aging in both mouse and human oocytes.
2022-05-04 | GSE173598 | GEO
Project description:Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that spermidine level was reduced in aged ovaries and supplementation of spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By micro-transcriptomic analysis, we further discovered that recovery of oocyte quality by spermidine was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this action mechanism was conserved in porcine oocytes under oxidative stress. Altogether, our findings demonstrate that spermidine supplementation is a potentially effective strategy to ameliorate oocyte quality and reproductive outcome of women at an advanced age.
2023-11-10 | GSE239551 | GEO
Project description:Here we asked if oocyte proteomes are representative of the transcriptomes, how the abundance of specific genes’ mRNA and protein responds to maternal aging, and if oocyte aging presents the features characteristic of somatic aging. To address these questions on the proteomic level, we employed stable isotope labeling of amino acids in cell culture (SILAC; Geiger et al. 2011) as the method of choice, and performed a SILAC screen of mouse metaphase II (MII) oocytes superovulated at 3, 8+-1 and 58+-10 weeks of maternal age, which correspond to pre-puberty, mature age and climacterium, respectively. We used heavy F9 embryonic carcinoma (EC) cells as internal or "Spike-in" standard for the quantification of oocytes proteins because in contrast to the oocytes they can easily be cultured feeder-free, have stem cell properties and should harbor the majority of all oocyte proteins (although with different relative abundances). The SILAC screen was conducted in parallel with conventional microarray analysis to compare the concordance of protein and transcript levels in these oocytes. Associated microarray data have been deposited to NCBI GEO with accession number GSE42959.
2016-10-14 | PXD000512 | Pride
Project description:Advanced maternal age, defined as 35 years or older, is associated with a decline in both ovarian reserve and oocyte quality, which leads to the female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetric complications. At present, the effective approaches to counteract the maternal age-related decay of oocyte quality are still not fully determined. Here, we report that in vivo supplementation of nicotinamide mononucleotide (NMN) efficaciously ameliorates the quality of oocytes from naturally aged mice by recovering nicotinamide adenine dinucleotide (NAD + ) levels in oocytes. NMN supplementation increases the number of antral follicles, ovulated oocytes and matured oocytes from aged mice. Specifically, NMN supplementation maintains the normal spindle/chromosome structure and dynamics of cortical granule component ovastacin to ensure the meiotic competency and fertilization ability of aged oocytes. Moreover, single cell transcriptome analysis shows that the beneficial effect of NMN on the aged oocytes is mediated by the restoration of the mitochondrial function, thereby reducing the accumulated ROS to suppress the occurrence of apoptosis. To sum up, our data reveal that supplementation of NMN is a feasible approach to prevent oocyte quality from advanced maternal age-related deterioration, contributing to improve the reproductive outcome of aged women and the assisted reproductive technology.
2023-07-01 | GSE153920 | GEO
Project description:Chromosome aneuploidy increases in oocytes with maternal age, and is considered the leading cause for the increased incidence of infertility, miscarriage, and birth defects. Using mRNA-Sequencing of oocytes from 12 month old mouse versus 3 month young mouse, we identified a spindle assembly checkpoint gene, BubR1, whose expression was significantly decreased. We employed a mRNA microinjection based approach to increase BubR1 expression in aging oocytes. We find that increased expression of BubR1 protects against aneuploidy and chromosome misalignment in aging oocytes. After in vitro fertilization, the embryos derived from BubR1 increased expression aging oocytes exhibited chromosome stability as robust as those of the young ones. Furthermore, following embryo transfer, these embryos showed greatly improved developmental competency, with comparable levels of full-term development to those of the young ones. These results indicate that the decline in oocyte quality may be reversible and could lead to treatments that prolong female fertility. Examination of the effect of maternal aging on the mRNA expression in the mature oocytes of the female mice. Naturally ovulated mature oocytes (MII stage) were collected from 6 young (3 month) and 6 aging (12 month) female mice (3 oocytes per mice, 18 oocytes for each group).
2014-05-10 | E-GEOD-57482 | biostudies-arrayexpress
Project description:Reproductive aging occurs earlier than systemic aging as a woman’s ovarian reserve is depleted as she approaches menopause. There is considerable variability around when a woman reaches menopause, yet few contributing factors have been identified. Assessment of reproductive age involves measuring a woman’s ovarian reserve and oocyte function, which has clearly-defined parameters in in vitro fertilization. As ovarian reserve declines, Anti-Mullerian hormone levels fall and women produce fewer oocytes after ovarian stimulation. Oocyte function also declines, as fewer mature oocytes are produced and have the capacity to be fertilized. The mechanisms of these age-related declines are unclear, but may involve changes in DNA methylation, which are known to occur with age and may reflect the biological processes underlying reproductive aging. We hypothesize that DNA methylation patterns will be associated with ovarian reserve and oocyte function, and that women with poor ovarian reserve and oocyte function will experience epigenetic age acceleration and will accumulate more stochastic epigenetic mutations. To test this hypothesis, we will first perform an epigenome-wide association to examine DNA methylation patterns associated with each measure of ovarian reserve and oocyte function. Then, we will calculate epigenetic age and age acceleration, which are indicators of biological aging, and stochastic epigenetic mutations, which increase with age and may disrupt key biological pathways in an individual.
2026-03-27 | GSE293125 | GEO
Project description:<p>Advanced maternal age is a key factor in female infertility, primarily due to declines in ovarian reserve and oocyte quality. However, the metabolic mechanisms underlying reproductive aging are still poorly understood. Here, we show that uridine levels in the plasma and ovaries of aged mice are significantly reduced compared with young controls. Building on this, we find that uridine supplementation significantly improves meiotic maturation, fertilization, and early embryonic development of aged oocytes, both in vivo and in vitro. Further microtranscriptomic analyses reveal that uridine enhances oocyte quality by inhibiting ferroptosis, enhancing mitochondrial function and removing excessive reactive oxygen species (ROS). Moreover, integrating Limited Proteolysis-Small Molecule Mapping (LiP-SMap), surface plasmon resonance (SPR) analyses and siRNA-based functional assays, we identify that uridine binds Poly(rC)-binding protein 1 (PCBP1), thereby suppressing ferroptosis and preserving mitochondrial function. In conclusion, this study demonstrates that uridine supplementation can effectively improve fertility of aged female mice. Our research also provides important insights into the role of ferroptosis in oocyte aging, thereby advancing our understanding of reproductive aging mechanisms.</p>
2026-03-03 | MTBLS13957 | MetaboLights
Project description:Advanced maternal age is a key factor in female infertility, primarily due to declines in ovarian reserve and oocyte quality. However, the metabolic mechanisms underlying reproductive aging remain unclear. Here, we show that uridine levels in the plasma and ovaries of aged mice are significantly reduced compared with young controls. Building on this, we find that uridine supplementation significantly improves meiotic maturation, fertilization, and early embryonic development of aged oocytes, both in vivo and in vitro. Further microtranscriptomic analyses reveal that uridine enhances oocyte quality by inhibiting ferroptosis and enhancing mitochondrial function. Moreover, integrating Limited Proteolysis-Small Molecule Mapping, western blot and siRNA-based functional assays, we identify that uridine binds Poly(rC)-binding protein 1, thereby suppressing ferroptosis and preserving mitochondrial function. Collectively, these findings demonstrate that uridine supplementation improves fertility in aged female mice and provide mechanistic insight into ferroptosis in oocyte aging.
2026-03-05 | PXD075265 | Pride
Project description:The degradation of maternal factors is essential for oocyte-to-embryo transition (OET). While extensive research has focused on maternal mRNA degradation, the mechanisms underlying maternal protein degradation remain poorly understood. ELVAs, the oocyte-specific membraneless structure which comprises proteasomes, endolysosomes and autophagosomes, are required for protein degradation in maturing oocytes and zygotes. In this study, we embloyed oocyte-specific Psma7 knockout, targeting the α4 subunit of 20S proteasome, to investigate the physiological function of proteasomes in ELVAs-mediated protein degradation. PSMA7-deficiency destabilizes 20S proteasome components and disrupts ELVAs assembly and spatial organization, resulting in the accumulation of ubiquitinated proteins in both oocytes and zygotes. Consequently, maternal PSMA7-deletion results in female infertility, manifested by impaired oocyte maturation and developmental arrest at the 1- to 2-cell stage. Furthermore, in oocytes from both aged mice and women, reduced proteasome abundance and aberrations in ELVAs distribution and activity were found, providing a mechanistic explanation for the diminished developmental competence aged oocytes. Taken together, our findings elucidate the critical function of proteasome-regulated proteostasis in oocyte quality control during OET and reproductive aging in females.
2026-04-27 | GSE293047 | GEO
Project description:To find genes in C. elegans oocytes associated with reproductive aging. Five replicates comparing RNA from oocyte samples collected from day 3 fem-1(hc17) animals with RNA from oocyte samples collected from day 8 fem-1(hc17) animals. Three out of five are dye-flipped.
2010-09-01 | E-GEOD-23447 | biostudies-arrayexpress