Maternal administration of acetaminophen affects meiosis through its metabolite NAPQI targeting SIRT7 in fetal oocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA944103 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23826702_1.fastq.gz | Fastqsanger.gz | |||
| SRR23826702_2.fastq.gz | Fastqsanger.gz | |||
| SRR23826703_1.fastq.gz | Fastqsanger.gz | |||
| SRR23826703_2.fastq.gz | Fastqsanger.gz | |||
| SRR23826704_1.fastq.gz | Fastqsanger.gz |
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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.
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Project description:The development of a haploid, fertilizable female gamete involves specialized meiotic divisions of the fully grown oocyte. An essential feature of oocyte meiosis is the reduction of genomic content to half, which is achieved by two successive divisions without an intervening S-phase. A known regulator of this event is a kinase called Mos that is exclusively expressed in oocytes during meiosis and activates the MEK/ERK/MAPK pathway. However, the downstream targets of the Mos-MAPK pathway and their significance in oocyte meiosis remains largely understudied. In this project, using phosphoproteomics on starfish (Patiria miniata) oocytes, we identify two predominant subsets of proteins that are targeted by Mos-MAPK at the critical time point - metaphase of meiosis I. These include proteins involved in CPE-mediated polyadenylation and cytoskeleton regulators. To complement this experiment, we performed DIA proteomics on Mos inhibited (20 micromolar U0126) and control oocytes at subsequent stages of meiosis (at 36 mins, 60 minutes and 90 minutes post hormone addition in U0126 inhibited oocytes and at metaphase I, meiosis I to meiosis II transition, metaphase II, 2 pronuclei and finally at the first mitotic division of the zygote for control oocytes). In this experiment, we identified 7,480 protein groups of which 5,103 protein groups could be quantified. We did not find significant changes in protein abundance across these time points and conditions, indicating that the proteome of starfish oocytes remains largely stable during meiosis.
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Project description:RNA-Seq can comprehensively and quickly obtain almost all transcripts and information of specific cells in rustic states.Here,we compared up-regulated genes in GV and MII oocytes from LSM14b deficient mice and wild-type mice by RNA-Seq,highlighting the important role of LSM14b in meiosis of mouse oocytes.
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Project description:We used 4D-DIA technology to sequence the proteome of yak oocytes at four stages, germinal vesicle, germinal vesicle breakdown, meiosis I, and meiosis Ⅱ, and identified 5,851 proteins; the expression of 1,012 proteins was significantly altered in multiple stages of meiosis.
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Project description:Meiosis is a specialized cell cycle that requires sequential changes to the cell division machinery to facilitate changing functions. To define the mechanisms that enable the oocyte-to-embryo transition, we performed time-course proteomics in sea star oocytes from prophase I through the first embryonic cleavage. Although protein levels are broadly stable, dynamic waves of phosphorylation underlie each meiotic stage. We find that the phosphatase PP2A-B55 is reactivated at the Meiosis I/II transition resulting in the preferential dephosphorylation of threonine residues. Selective dephosphorylation is critical for directing the MI / MII transition as altering PP2A-B55 substrate preferences disrupts key cell cycle events after meiosis I. In addition, threonine to serine substitution of a conserved phosphorylation site in the substrate INCENP prevents its relocalization at anaphase I. Thus, through its inherent phospho-threonine preference, PP2A-B55 imposes specific phosphoregulated behaviors that distinguish the two meiotic divisions.
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Project description:Oocytes develop the competence for meiosis and early embryogenesis during their growth. Setdb1 is a histone H3 lysine 9 (H3K9) methyltransferase required for post-implantation development and has been implicated in the transcriptional silencing of genes and endogenous retroviral elements (ERVs). To address its role in oogenesis and pre-implantation development, we conditionally deleted Setdb1 in growing oocytes. Loss of Setdb1 expression greatly impaired meiosis. It delayed meiotic resumption, altered the dynamics of chromatin condensation, and impaired kinetochore-spindle interactions, bipolar spindle organization, and chromosome segregation in more mature oocytes. The observed phenotypes related to changes in abundance of specific transcripts in mutant oocytes. Setdb1 maternally deficient embryos arrested during pre-implantation development and showed comparable defects during cell cycle progression and in chromosome segregation. Finally, transcriptional profiling data indicate that Setdb1 down-regulates rather than silences expression of ERVK and ERVL-MaLR retrotransposons and associated chimearic transcripts during oogenesis. Our results identify Setdb1 as a novel meiotic and embryonic competence factor in meiosis and mitosis, safeguarding genome integrity at the onset of life. We performed expression profiling on pools of 16 denuded GV-oocytes isolated per mouse. We used oocytes from 4 Setdb1 f/+; Zp3-cre mice and 2 Setdb1 f/- mice as controls and oocytes from 4 Setdb1 f/-; Zp3-cre mice as mutant.
2016-06-27 | E-GEOD-82002 | biostudies-arrayexpress
Project description:Oocytes develop the competence for meiosis and early embryogenesis during their growth. Setdb1 is a histone H3 lysine 9 (H3K9) methyltransferase required for post-implantation development and has been implicated in the transcriptional silencing of genes and endogenous retroviral elements (ERVs). To address its role in oogenesis and pre-implantation development, we conditionally deleted Setdb1 in growing oocytes. Loss of Setdb1 expression greatly impaired meiosis. It delayed meiotic resumption, altered the dynamics of chromatin condensation, and impaired kinetochore-spindle interactions, bipolar spindle organization, and chromosome segregation in more mature oocytes. The observed phenotypes related to changes in abundance of specific transcripts in mutant oocytes. Setdb1 maternally deficient embryos arrested during pre-implantation development and showed comparable defects during cell cycle progression and in chromosome segregation. Finally, transcriptional profiling data indicate that Setdb1 down-regulates rather than silences expression of ERVK and ERVL-MaLR retrotransposons and associated chimearic transcripts during oogenesis. Our results identify Setdb1 as a novel meiotic and embryonic competence factor in meiosis and mitosis, safeguarding genome integrity at the onset of life.
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Project description:Human meiosis in oocytes entails a fine regulation of the transcriptome to support late oocyte growth and early embryo development, both key to reproductive success. Currently, little is known about the co- and post-transcriptional mRNA processing mechanisms regulating the last meiotic passages, which contribute to transcriptome complexity and influence translation rates. We analyzed gene expression changes, splicing and pre-mRNA processing in an RNA sequencing set of 40 oocytes at different meiotic maturation stages, both in vivo ovulated and matured in vitro. We found abundant UTR processing, mostly at the 3’-, of meiosis-related genes between the stages of GV and MII, supported by the differential expression of spliceosome and pre-mRNA processing related genes. Importantly, we found very little differences among GV oocytes across several lengths of in vitro maturation, as long as they did not reach MII, suggesting a specific association of RNA processing and successful meiosis transit. Changes in protein isoforms are minor, though specific and consistent for genes involved in chromosome organization and spindle assembly. In conclusion, we reveal a dynamic transcript remodeling during human female meiosis, and show how pre-mRNA processing, specifically 3’-UTR shortening, drives a selective translational regulation of transcripts necessary to reach the final meiotic maturation.
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