Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age
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ABSTRACT:
PROVIDER: PRJNA718570 | ENA |
REPOSITORIES: ENA
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Project description:The frequency of egg aneuploidy and trisomic pregnancies increases with maternal age. To what extent individual approaches can delay the “maternal age effect” is unclear since multiple causes contribute to chromosomal abnormalities in mammalian eggs. We propose that ovulation frequency determines the physiological ageing of oocytes, a key aspect of which is the ability to accurately segregate chromosomes and produce euploid eggs. To test this hypothesis, ovulations were reduced using successive pregnancies, hormonal contraception and a pre-pubertal knockout mouse model, and the effects on chromosome segregation and egg ploidy were examined. We show that each intervention reduces chromosomal abnormalities in eggs of aged mice, suggesting that ovulation reduction delays oocyte ageing. The protective effect can be partly explained by retention of chromosomal Rec8-cohesin that maintains sister chromatid cohesion in meiosis. In addition, single-nucleus Hi-C (snHi-C) revealed a deterioration in 3D chromatin structure including an increase in extruded loop sizes in long-lived oocytes. Artificial cleavage of Rec8 is sufficient to increase extruded loop sizes, suggesting that cohesin complexes maintaining cohesion restrict loop extrusion. These findings suggest that ovulation suppression protects against Rec8 loss, thereby maintaining both sister chromatid cohesion and 3D chromatin structure and promoting production of euploid eggs. We conclude that the “maternal age effect” can be delayed in mice. An implication of this work is that long-term ovulation-suppressing conditions can potentially reduce the risk of Down’s syndrome pregnancies at advanced maternal age.
2021-07-27 | GSE171159 | GEO
Project description:Multiple mechanisms likely contribute to the increase in chromosome missegregation that leads to production of aneuploid eggs and fetuses at advanced maternal age. It is therefore considered unlikely that a single approach could prevent age-related egg aneuploidy. Here we show using three independent approaches that ovulation reduction is sufficient to prevent egg aneuploidy in aged mammals. To gain insights into the mechanism underlying the rescue in egg aneuploidy, we show that ovulation suppression correlates with retention of chromosomal Rec8-cohesin, implying that ovulations are linked to cohesin deterioration. Moreover, we discovered that ageing alters 3D chromatin organization by single-nucleus Hi-C (snHi-C). Extruded loops increase in size with age and this is retarded by ovulation reduction. We conclude that reducing ovulations leads to retention of chromosomal Rec8, which maintains interphase chromatin structure and promotes chromosome segregation and production of euploid eggs. Importantly, our data suggest that ovulation itself contributes to the maternal age effect. This work provides the first experimental evidence that progesterone treatment reduces egg aneuploidy and suggests that hormonal contraception can reduce the risk of trisomic pregnancies like Down’s syndrome at advanced maternal age.
2021-04-01 | GSE130585 | GEO
Project description:The present study aimed at studying the rainbow trout egg transcriptome using 9152-cDNA microarrays after natural or controlled ovulation. The analysis of egg transcriptome after natural or controlled ovulation led to the identification of 26 genes. We observed that both hormonal induction and photoperiod control of ovulation induced significant changes in the egg mRNA abundance of specific genes. We demonstrate that hormonal induction of ovulation has an impact on the egg mRNA abundance of specific genes even though the resulting effects on the developmental potential of the egg is so far unknown. In addition, we also identified 1 gene exhibiting a differential mRNA abundance in eggs of varying developmental potential. Analysis of egg transcriptome after natural ovulation (4 samples), photoperiod-controlled ovulation (14 samples), and hormonally-induced ovulation (11 samples).
2010-07-01 | E-GEOD-5928 | biostudies-arrayexpress
Project description:The present study aimed at studying the rainbow trout egg transcriptome using 9152-cDNA microarrays after natural or controlled ovulation. The analysis of egg transcriptome after natural or controlled ovulation led to the identification of 26 genes. We observed that both hormonal induction and photoperiod control of ovulation induced significant changes in the egg mRNA abundance of specific genes. We demonstrate that hormonal induction of ovulation has an impact on the egg mRNA abundance of specific genes even though the resulting effects on the developmental potential of the egg is so far unknown. In addition, we also identified 1 gene exhibiting a differential mRNA abundance in eggs of varying developmental potential. Keywords: Egg quality-dependent
2006-10-03 | GSE5928 | GEO
Project description:Chromosomal abnormalities are important causes of miscarriages. To delinate the chromosomal abnormalities in miscarriages, 564 miscarriages were collected and analyzed using single nucleotide polymorphism (SNP) array. 336 (59.6%) miscarriages were with abnormal copy number variations (CNVs), including 325 (57.6%) miscarriages with pathogenic CNVs and 11 (2%) miscarriages with variations of unknown significance (VOUS). The remaining 228 (40.4%) miscarriages had no clinically relevant chromosomal variants.
2023-05-21 | GSE207887 | GEO
Project description:Four separate biological collections of unfertilized eggs laid by wildtype females mated with sterile males, eggs dechorionated and snap-forzen in liquid nitrogen 0-1 hour after egg lay. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
2005-09-10 | GSE3287 | GEO
Project description:Egg quality is an important aspect in rainbow trout farming. Post-ovulatory aging is one of the most important factors affecting egg quality. MicroRNAs (miRNAs) are the major regulators in various biological processes and their expression profiles could serve as reliable biomarkers for various pathological and physiological conditions. Egg samples from 32 females on day 1, day 7, and day 14 post-ovulation (D1PO, D7PO and D14PO), which had the fertilization rates of 91.8%, 73.4% and less than 50%, respectively, were collected and small RNAs isolated from these samples were subjected to deep sequencing using the Illumina platform. Six miRNAs were found to be differentially expressed between D1PO and D14PO eggs. GO analysis of the target genes of the 6 miRNAs that were down-regulated in D14PO eggs revealed significantly enriched GO terms that are related to stress response, cell death, DNA damage, ATP generation, signal transduction and transcription regulation. Examination of small RNA populations in eggs of different qualities caused by post-ovulatory aging.
2015-02-18 | E-GEOD-65990 | biostudies-arrayexpress
Project description:Egg quality is an important aspect in rainbow trout farming. Post-ovulatory aging is one of the most important factors affecting egg quality. MicroRNAs (miRNAs) are the major regulators in various biological processes and their expression profiles could serve as reliable biomarkers for various pathological and physiological conditions. Egg samples from 32 females on day 1, day 7, and day 14 post-ovulation (D1PO, D7PO and D14PO), which had the fertilization rates of 91.8%, 73.4% and less than 50%, respectively, were collected and small RNAs isolated from these samples were subjected to deep sequencing using the Illumina platform. Six miRNAs were found to be differentially expressed between D1PO and D14PO eggs. GO analysis of the target genes of the 6 miRNAs that were down-regulated in D14PO eggs revealed significantly enriched GO terms that are related to stress response, cell death, DNA damage, ATP generation, signal transduction and transcription regulation.
2015-02-18 | GSE65990 | GEO
Project description:Four separate biological collections of unfertilized eggs laid by wildtype females mated with sterile males, eggs dechorionated and snap-forzen in liquid nitrogen 0-1 hour after egg lay. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
2005-09-10 | E-GEOD-3287 | biostudies-arrayexpress
Project description:Molecular profiling of the eggs is an excellent approach aiming at understanding biological processes and mechanisms conditioning developmental competence in finfishes and, consequently, reproductive fitness. Despite many efforts, it is still unclear what is the specific role of transcriptome and proteome in determination of egg quality in Teleostei fishes. The aim of this study was to perform integrated transcriptomic-proteomic analysis of eggs of pikeperch – a commercially relevant freshwater fish species. Additionally, comparative analysis of transcriptome and proteome in eggs characterized by either high or low egg quality has been performed, in order to identify mechanisms leading to early embryonic lethality in pikeperch. Our study provides a novel insight into the understanding of the role of maternally-derived molecular cargo in finfishes. The data obtained sheds light on the importance of transcriptome in development of nervous system suggesting neurogenesis-related mRNAs as a very important, non-genetic inheritance factor. Proteomic analysis highlights specific role of proteins in the immune response in ovulated eggs. Integrated analysis brings attention to the galactose-specific lectin nattectin gene and protein as the frontline defense molecule for the egg and developing embryo. The molecular analysis of egg developmental competence emphasizes post-vitellogenic processes (final oocyte maturation and ovulation) as the ones potentially compromising transcriptomic profile, but not affecting proteomic cargo. It highlights the need for careful reconsideration of the commercial reproductive protocols as the very strong modulators of egg quality and their molecular profile. Considering the mechanisms driving these alterations as well as consequences stemming from the differential abundance of the transcripts are still to be explored, the candidate quality markers, first time provided for pikeperch along with the current study, are creating valuable resource for further studies.
2021-10-01 | GSE167376 | GEO