Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Nikolai Slavov Montserrat Barragan Monasterio
PROVIDER: MSV000093870 | MassIVE | Mon Jan 15 14:38:00 GMT 2024
REPOSITORIES: MassIVE
Publications
Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes.
Galatidou Styliani S Petelski Aleksandra A AA Pujol Aïda A Lattes Karinna K Latorraca Lais B LB Fair Trudee T Popovic Mina M Vassena Rita R Slavov Nikolai N Barragán Montserrat M
Molecular human reproduction 20240601 7
Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed data-independent acquisition, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between imm ...[more]
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Project description: Not available
| S-EPMC12106276 | biostudies-literature
Project description:STUDY QUESTION: Does maternal age affect the maturated oocyte quality and the fol-lowing development after fertilization in human? SUMMARY ANSWER: Maternal age affects the quality of maturated oocytes by altering the stored mRNA levels in human, such as TOP2B. WHAT IS KNOWN ALREADY: Intracellular mRNAs in maturated oocytes are tran-scripted from the maternal genome during oogenesis and important for the zygotic genome activation (ZGA) after fertilization. Microarray data showed that maternal age affected polyadenylated transcript abundance in human oocytes. These genes are involved in in signaling pathway related to cell cycle regulation, chromosome alignment. However, which genes are the key genes affected by maternal age and important for the development after fertilization had not been reported. Therefore, single-cell RNA sequencing (scRNA-Seq) technology is employed in this study to screen the key genes affected by maternal age in human maturated oocytes. STUDY DESIGN, SIZE, DURATION: We isolated mRNA from maturated (MII) oo-cytes donated by IVF or ICSI patients (three oocytes from young (≤ 30 years) and three oocytes from advanced maternal age (≥ 40 years) patients) undergoing controlled ovarian stimulation. Thus, a total of six maturated oocytes were individually processed for scRNA-seq analysis. The key genes screened from scRNA-seq analysis are confirmed using mouse model. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing infertility treatment at the Yuhuangding Hospital of Yantai underwent ovarian stimulation with FSH and received hCG for final follicular maturation prior to ul-trasound guided oocyte retrieval. We isolated RNA, generated single cell RNA-seq librar-ies (Smart-Seq2) and sequenced by Illumina Hiseq X-ten platform with 150 bp paired-end. Bioinformatics analysis of the sequencing data was done to find the biological processes and key genes that led to the decline in the quality of oocytes with advanced maternal age. To validate the findings, we used mouse model and validated candidate genes by RT-PCR and knockdown experiments. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 1439 genes differentially expressed between older and younger women's maturated oocytes (|foldchange|>2, P < 0.05). These genes are significantly enriched with annotations related to transporter activity, cytoskeleton, oxidative stress, catalytic activity, immune function, cellular senescence and biosynthesis. The key candidate gene TOP2B was found by protein interaction network analysis, and knockdown verification on young mouse maturated oocytes showed that TOP2B was a key gene affecting the oocyte quality and disturbing early embryo development. LARGE SCALE DATA Raw data from this study can be accessed through GSE. LIMITATIONS, REASONS FOR CAUTION: The human maturated oocytes used in this study were from patients with different causes of infertility and may affect oocyte gene expression. In addition, the study was based on a lim-ited number of patients, and there are possible natural biological variance existed in human samples. WIDER IMPLICATIONS OF THE FINDINGS: For the first time, we used scRNA-seq to detect global gene transcriptome of maturated oocytes in young and older women. These results are useful to indicate the molecular mechanisms of female ovary aging and establishing a criterion to evaluate the quality of oocytes in women with advanced maternal age. STUDY FUNDING/COMPETING INTERESTS: This research was supported by the National Key Research and Development Program of China (2018YFC1004304, 2016YFA0100203), Medical and Health Science Technology Development Plan Project of Shandong Province (Grant#. 2017WS566). There are no competing interests.
2019-01-19 | GSE125300 | GEO
Project description:<p>The gut microbiota plays a vital role in maintaining the physiological function of host health and the pathogenesis of various diseases. However, its relationship with maternal age-associated decline in oocyte quality remains elusive. Here, we report that establishment of gut microbiota from young donors in aged mice by fecal microbiota transplantation (FMT) is an effective method to rejuvenate the quality of maternally aged oocytes. Specifically, young gut microbiota promoted the ovulation and maturation of aged oocytes, and inhibited occurrence of cytoplasm fragmentation and spindle/chromosome abnormalities, hence enhancing the oocyte quality and female fertility. By integrating metagenome and untargeted metabolome of intestinal digesta, as well as targeted metabolome of ovaries and micro-transcriptome of oocytes, we identified that Bacteroides_caecimuris-modulated glutamic acid levels mediated the restorative effects of young gut microbiota on the aged oocytes through strengthening the mitochondria function. In addition, we demonstrated that in vivo supplementation of glutamic acid also enhanced the quality of aged oocytes, and the improvement of oocyte quality by glutamic acid was conserved across species. Altogether, our findings highlight the importance of gut microbiota in the oocyte aging and provide potential improvement strategies for age-related decline in oocyte quality and female fertility.</p>
2026-05-07 | MTBLS14062 | MetaboLights
Project description:Study Question: What effects do maternal age and oocyte maturation stage have on the human oocyte transcriptome that may be associated with oocyte developmental potential? Summary Answer: Although polyadenylated transcript abundance changes during human oocyte maturation irrespective of age, young (YNG) and advanced maternal age (AMA) metaphase II (MII) oocytes exhibit divergent transcriptomes. What is known already: Maternal age and maturation stage affect oocyte polyadenylated transcript abundance in human oocytes. Although RNA-Seq analysis of single human MII oocytes has been conducted, comparison of the germinal vesicle (GV) and MII oocyte transcriptomes has not been investigated using RNA-Seq, a technique that could provide novel insight into oocyte maturation and age-associated aberrations in gene expression. Participants / materials, settings, methods: Patients undergoing infertility treatment at the Colorado Center for Reproductive Medicine (Lone Tree, CO, USA) underwent ovarian stimulation with FSH and received hCG for final follicular maturation prior to ultrasound guided egg retrieval. Unused GV oocytes obtained at retrieval were donated for transcriptome analysis. Single oocytes were stored (at -80°C in PicoPure RNA Extraction Buffer; Thermo Fisher Scientific, USA) immediately upon verification of immaturity or after undergoing in vitro oocyte maturation (24 hour incubation), representing GV and MII samples, respectively. After isolating RNA and generating single oocyte RNA-Seq libraries (SMARTer Ultra Low Input RNA HV kit; Clontech, USA), Illumina sequencing (100 bp paired-end reads in HiSeq 2500) and bioinformatics analysis (CLC Genomics Workbench, DESeq2, Weighted Gene Correlation Network Analysis (WGCNA), 3’UTR motif analysis, Ingenuity Pathway Analysis) were performed. Main results and the role of chance: Within the 12,770 expressed genes in human oocytes (reads per kilobase per million mapped reads (RPKM) > 0.4 in at least 3 of 5 replicates for a minimum of one sample type), 458 and 3,506 genes significantly (adjusted p < 0.05 and log2 fold change > 1) increased and decreased in polyadenylated transcript abundance during oocyte maturation, respectively. The differentially expressed genes were enriched (FDR < 0.05) for biological functions and canonical pathways related to cell cycle and mitochondrial function. The majority (76%) and minority (25%) of up- and down-regulated transcripts with a complete 3’UTR were predicted to be targets of cytoplasmic polyadenylation (910 total genes), respectively. Differential gene expression analysis between young and advanced maternal age oocytes (within stage) identified 1 and 255 genes that significantly differed (adjusted p < 0.1 and log2 fold change > 1) in polyadenylated transcript abundance for GV and MII oocytes, respectively. These genes included CDK1, NLRP5, and PRDX1, which have been reported to affect oocyte developmental potential and be markers of oocyte quality. Despite similarity in transcript abundance between GV oocytes irrespective of age, divergent expression patterns emerged during oocyte maturation. These age-specific differentially expressed genes were enriched (FDR < 0.05) for functions and pathways associated with mitochondria, cell cycle, and cytoskeleton. Gene modules generated by WGCNA (based on gene expression) and patient traits related to oocyte quality (e.g. age and blastocyst development) were determined to be correlated (p < 0.05) and enriched (FDR < 0.05) for functions and pathways associated with oocyte maturation. Limitations, reasons for caution: The human oocytes used in the current study were obtained from patients with varying causes of infertility (e.g. decreased oocyte quality and oocyte quality-independent factors), possibly affecting oocyte gene expression. Oocytes in this study were retrieved at the GV stage following hCG administration and the MII oocytes were derived by in vitro maturation of patient oocytes, which has the benefit of identifying intrinsic differences between samples, but may not be completely representative of in vivo matured oocytes. Thus, these factors should be considered when interpreting the results. Wider Implications of the findings: Transcriptome profiles of young and advanced maternal age oocytes, particularly at the MII stage, suggest aberrant transcript abundance contributes to the age-associated decline in fertility.
2018-04-12 | GSE95477 | GEO
Project description:The gut microbiota plays a vital role in maintaining the physiological function of host health and the pathogenesis of various diseases. However, its relationship with maternal age-associated decline in oocyte quality remains elusive. Here, we report that establishment of gut microbiota from young donors in aged mice by fecal microbiota transplantation (FMT) is an effective method to rejuvenate the quality of maternally aged oocytes. Specifically, young gut microbiota promoted the ovulation and maturation of aged oocytes, and inhibited occurrence of cytoplasm fragmentation and spindle/chromosome abnormalities, hence enhancing the oocyte quality and female fertility. By integrating metagenome and untargeted metabolome of intestinal digesta, as well as targeted metabolome of ovaries and micro-transcriptome of oocytes, we identified that Bacteroides_caecimuris-modulated glutamic acid levels mediated the restorative effects of young gut microbiota on the aged oocytes through strengthening the mitochondria function. In addition, we demonstrated that in vivo supplementation of glutamic acid also enhanced the quality of aged oocytes, and the improvement of oocyte quality by glutamic acid was conserved across species. Altogether, our findings highlight the importance of gut microbiota in the oocyte aging and provide potential improvement strategies for age-related decline in oocyte quality and female fertility.
2026-04-24 | GSE324538 | GEO
Project description:The gut microbiota plays a vital role in maintaining the physiological function of host health and the pathogenesis of various diseases. However, its relationship with maternal age-associated decline in oocyte quality remains elusive. Here, we report that establishment of gut microbiota from young donors in aged mice by fecal microbiota transplantation (FMT) is an effective method to rejuvenate the quality of maternally aged oocytes. Specifically, young gut microbiota promoted the ovulation and maturation of aged oocytes, and inhibited occurrence of cytoplasm fragmentation and spindle/chromosome abnormalities, hence enhancing the oocyte quality and female fertility. By integrating metagenome and untargeted metabolome of intestinal digesta, as well as targeted metabolome of ovaries and micro-transcriptome of oocytes, we identified that Bacteroides_caecimuris-modulated glutamic acid levels mediated the restorative effects of young gut microbiota on the aged oocytes through strengthening the mitochondria function. In addition, we demonstrated that in vivo supplementation of glutamic acid also enhanced the quality of aged oocytes, and the improvement of oocyte quality by glutamic acid was conserved across species. Altogether, our findings highlight the importance of gut microbiota in the oocyte aging and provide potential improvement strategies for age-related decline in oocyte quality and female fertility.
2026-04-24 | GSE325001 | GEO
Project description:The gut microbiota plays a vital role in maintaining the physiological function of host health and the pathogenesis of various diseases. However, its relationship with maternal age-associated decline in oocyte quality remains elusive. Here, we report that establishment of gut microbiota from young donors in aged mice by fecal microbiota transplantation (FMT) is an effective method to rejuvenate the quality of maternally aged oocytes. Specifically, young gut microbiota promoted the ovulation and maturation of aged oocytes, and inhibited occurrence of cytoplasm fragmentation and spindle/chromosome abnormalities, hence enhancing the oocyte quality and female fertility. By integrating metagenome and untargeted metabolome of intestinal digesta, as well as targeted metabolome of ovaries and micro-transcriptome of oocytes, we identified that Bacteroides_caecimuris-modulated glutamic acid levels mediated the restorative effects of young gut microbiota on the aged oocytes through strengthening the mitochondria function. In addition, we demonstrated that in vivo supplementation of glutamic acid also enhanced the quality of aged oocytes, and the improvement of oocyte quality by glutamic acid was conserved across species. Altogether, our findings highlight the importance of gut microbiota in the oocyte aging and provide potential improvement strategies for age-related decline in oocyte quality and female fertility.
2026-04-24 | GSE324539 | GEO
Project description:Background: The development competence of human oocytes declines with increasing age. The objective of this study was to investigate the effect of age on gene expression profile in mature human oocytes.<br>Methods: mRNA was isolated for whole genome gene expression microarray analysis from metaphase II (MII) oocytes donated by IVF or ICSI patients (10 women aged <36 years (younger) and 5 women aged 36-39 years (both inclusive) (older)) undergoing controlled ovarian simulation
2009-12-31 | E-MEXP-2347 | biostudies-arrayexpress
Project description:Acetaminophen (APAP) is clinically recommended as analgesic and antipyretic among pregnant women. However, accumulating laboratory evidence shows that the use of APAP during pregnancy may alter fetal development. Since fetal stage is a susceptible window for early oogenesis, we aim to assess the potential effects of maternal administration of APAP on fetal oocytes. Maternal administration and the fetal ovary cultures showed that APAP (50 and 150 mg/kg.bw/day) caused meiotic aberrations in fetal oocytes through its metabolite NAPQI, including meiotic prophase I (MPI) progression delay and homologous recombination defects. Co-treatment with NAM or NRC, NAD+ supplements, efficiently restored the MPI arrest, while the addition of the inhibitor of SIRT7 invalidated the effect of the NAD+ supplement. Additionally, RNA sequencing revealed distorted transcriptomes of fetal ovaries treated with NAPQI. Further, the fecundity of female offspring was affected, exhibiting as delayed primordial folliculogenesis and puberty onset, reduced levels of ovarian hormones, and impaired developmental competence of MII oocytes. Short-term administration of APAP to pregnant mouse caused meiotic aberrations in fetal oocytes by its metabolite NAPQI, while co-treatment with NAD+ supplement efficiently relieves the adverse effects by interacting with SIRT7.
2023-03-18 | GSE227192 | GEO
Project description:TOP2B disturbed the quality of human oocytes with advanced maternal age
| PRJNA515815 | ENA