Spermidine promotes meiotic maturation of porcine oocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA899034 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22215320_1.fastq.gz | Fastqsanger.gz | |||
| SRR22215320_2.fastq.gz | Fastqsanger.gz | |||
| SRR22215321_1.fastq.gz | Fastqsanger.gz | |||
| SRR22215321_2.fastq.gz | Fastqsanger.gz |
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Project description:Spermidine is involved in a variety of biological processes, including DNA metabolism, autophagy and aging. Previous studies have shown that spermidine can increase the percentage of mouse oocytes developing into blastocysts after in vitro fertilization. However, none of the past studies elucidated the effects of spermidine supplementation on porcine oocyte maturation. Here, we choose appropriate dose of spermidine to be added to the maturation medium during in vitro maturation (IVM) to verify whether spermidine can actively promote the maturation of porcine oocytes. Our study provided substantial evidence that spermidine exposure promoted the porcine oocyte meiotic maturation. In addition, single-cell transcriptome analysis identified the target effectors of spermidine actions in porcine oocytes, further demonstrating that spermidine exposure enhanced mitochondrial distribution and function, leading to a reduced excessive oxidative stress-induced DNA damage and early apoptosis of porcine oocytes. These findings demonstrate that spermidine not only delays ageing and cancer treatment, but also improves the quality of germ cells, which may be less likely to suffer from sterility or infertility in humans and animals.
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Project description:Well-balanced and timed metabolism is the prerequisite for optimal oocyte development. To date, numerous studies have focused on the utilization of exogenous substrates by oocytes, whereas the underlying mechanism of intrinsic regulation during meiotic maturation is less characterized. Herein, we performed an integrated analysis of parallel metabolomics and transcriptomics by isolating porcine oocytes at three time points, cooperatively depicting the global picture of the metabolic patterns during oocyte maturation. In particular, we identified the metabolic features of porcine oocytes during meiotic maturation, such as the fall in bile acids, the active one-carbon metabolism and a progressive decline in nucleotide metabolism. Collectively, the current study not only provide a comprehensive multiple omics data resource, but also may promote the discovery of biomarkers in the prediction and improvement of oocyte quality.
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Project description:Poly(A) polymerase α (PAPα), as the specific mRNA polyadenylation enzyme in the cytoplasm of mammalian oocytes, is essential for oocytes to exclude the first polar body. However, PAPα knockout did not affect germinal vesicles breakdown (GVBD) of oocytes, and the mechanism needs to be further explored. In this study, we identified that PAPα work together with poly(A)-bound RNA binding protein PABPN1 to promote the rupture of germinal vesicles in mammalian oocytes. The protein level of Pabpn1 gradually increases with the meiotic maturation of oocytes. The oocytes specifically knocked out Pabpn1 at the primary follicle stage could develop into the fully grown (FGO) stage, but hardly could enter into the meiotic process. The activated form of CDK1 was injected into Pabpn1-null oocytes, the oocytes could enter into meiotic process. The translational activity of Pabpn1-null oocytes was significantly lower than that of wild-type oocytes during meiosis. In particular, the expression level of protein (BTG4 and CDC25), which were essential for the meiotic maturation of oocytes, were significantly decreased. Therefore, during the oocyte meiosis process, PABPN1 and PAPα jointly promote the oocyte to enter the meiosis process.
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Project description:SIRT6, the sixth member of sirtuin family proteins, has been identified as a crucial regulator in multiple molecular pathways related to aging, including genome stability, DNA damage repair, telomere maintenance and inflammation. However, the exact roles of SIRT6 during mammalian oocyte meiosis have not yet fully clarified. Here, we investigated the critical events during porcine oocyte meiotic maturation with the treatment of SIRT6 specific inhibitor SIRT6-IN-1. We found that SIRT6 inhibition resulted in oocyte meiotic failure by displaying the poor expansion of cumulus cells and reduced rate of polar body extrusion. Meanwhile, the compromised spindle assembly, chromosome alignment and actin dynamics were also observed in SIRT6-inhibited oocytes. Moreover, inhibition of SIRT6 led to the defective cytoplasmic maturation by showing the abnormal distribution of cortical granules and their component ovastacin. Notably, we identified that expression of genes related to oocyte meiosis, oxidative phosphorylation and cellular senescence was remarkably altered in SIRT6-inhibited oocytes by transcriptome analysis, and validated that the meiotic defects caused by SIRT6 inhibition resulted from the excessive ROS-induced early apoptosis in oocytes. Taken together, our findings demonstrate that SIRT6 promotes the porcine oocyte meiotic maturation via maintaining the organelle dynamics.
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