Journal ArticleDOI
The apoptotic transcriptome of the human MII oocyte: characterization and age-related changes
Manuela Santonocito,Maria Rosa Guglielmino,Marilena Vento,Marco Ragusa,Davide Barbagallo,Placido Borzì,Ida Casciano,Paolo Scollo,Massimo Romani,Carla Tatone,Michele Purrello,Cinzia Di Pietro +11 more
TLDR
During maturation the oocytes from older women selectively accumulate mRNAs that are able to trigger the extrinsic apoptotic pathway, and these data contribute to clarify the molecular mechanisms of AM involvement in the natural selection strategy of removing low quality oocytes and preventing unfit or poorly fit embryos.Abstract:
Fully competent oocytes represent the final outcome of a highly selective process. The decline of oocyte competence with ageing, coupled to quantitative decrease of ovarian follicles has been well established; on the contrary, its molecular bases are still poorly understood. Through quantitative high throughput PCR, we investigated the role of apoptotic machinery (AM) in this process. To this aim, we determined AM transcriptome in mature MII oocyte pools from women aged more than 38 years (cohort A), and compared to women aged up to 35 years (cohort B). Subsequently, 10 representative AM genes were selected and analyzed in 33 single oocytes (15 from cohort A and 18 from cohort B). These investigations led us to identify: (1) the significant upregulation of proapoptotic genes such us CD40, TNFRSF10A, TNFRSF21 and the downregulation of antiapoptotic genes such as BCL2 and CFLAR in cohort A respect to cohort B; (2) AM transcripts that have not previously been reported in human oocytes (BAG3, CD40, CFLAR, TNFRSF21, TRAF2, TRAF3). Our results demonstrated that during maturation the oocytes from older women selectively accumulate mRNAs that are able to trigger the extrinsic apoptotic pathway. These data contribute to clarify the molecular mechanisms of AM involvement in the natural selection strategy of removing low quality oocytes and preventing unfit or poorly fit embryos.read more
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Journal ArticleDOI
Impact of Maternal Age on Oocyte and Embryo Competence
Danilo Cimadomo,Gemma Fabozzi,Alberto Vaiarelli,Nicolò Ubaldi,Filippo Maria Ubaldi,Laura Rienzi +5 more
TL;DR: The main strategies proposed to improve the management of advanced maternal age women in IVF: fertility preservation through oocyte cryopreservation to prevent aging; optimization of the ovarian stimulation and enhancement of embryo selection to limit its effects; and oocyte donation to circumvent its consequences.
Journal ArticleDOI
Apoptosis in mammalian oocytes: a review.
Meenakshi Tiwari,Shilpa Prasad,Anima Tripathi,Ashutosh N. Pandey,Irfan Ali,Arvind Singh,Tulsidas G. Shrivastav,Shail K. Chaube +7 more
TL;DR: Oocyte apoptosis leads to the depletion of ovarian reserve that directly affects reproductive outcome of various mammals including human.
Journal ArticleDOI
Oocyte ageing and epigenetics
TL;DR: The relationship between ageing and epigenetic modifications is discussed, highlighting the epigenetic changes in oocytes from advanced-age females and in post-ovulatory aged oocytes as well as the possible underlying mechanisms.
Journal ArticleDOI
Chromothripsis: potential origin in gametogenesis and preimplantation cell divisions. A review.
TL;DR: The discovery of this new class of massive chromosomal rearrangement has deeply modified the authors' understanding on the genesis of complex genomic rearrangements and the assumption that chromothripsis could operate in human germlines and during early embryonic development is supported.
Journal ArticleDOI
MicroRNAs Are Stored in Human MII Oocyte and Their Expression Profile Changes in Reproductive Aging
Rosalia Battaglia,Maria Elena Vento,Marco Ragusa,Davide Barbagallo,Alessandro La Ferlita,Giovanna Di Emidio,Placido Borzì,Paolo Giovanni Artini,Paolo Scollo,Carla Tatone,Michele Purrello,Cinzia Di Pietro +11 more
TL;DR: It is proposed that oocyte miRNAs perform an important regulatory function in human female germ cells, and their altered regulation could explain the changes occurring in oocyte aging.
References
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Journal ArticleDOI
Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method
TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.
Journal ArticleDOI
Why do hubs tend to be essential in protein networks
Xionglei He,Jianzhi Zhang +1 more
TL;DR: The network analysis suggests that the centrality-lethality rule is unrelated to the network architecture, but is explained by the simple fact that hubs have large numbers of PPIs, therefore high probabilities of engaging in essential PPIs.
Why Do Hubs Tend to Be Essential in Protein
Abstract: The protein–protein interaction (PPI) network has a small number of highly connected protein nodes (known as hubs) and many poorly connected nodes. Genome-wide studies show that deletion of a hub protein is more likely to be lethal than deletion of a non-hub protein, a phenomenon known as the centrality-lethality rule. This rule is widely believed to reflect the special importance of hubs in organizing the network, which in turn suggests the biological significance of network architectures, a key notion of systems biology. Despite the popularity of this explanation, the underlying cause of the centrality-lethality rule has never been critically examined. We here propose the concept of essential PPIs, which are PPIs that are indispensable for the survival or reproduction of an organism. Our network analysis suggests that the centrality-lethality rule is unrelated to the network architecture, but is explained by the simple fact that hubs have large numbers of PPIs, therefore high probabilities of engaging in essential PPIs. We estimate that ~ 3% of PPIs are essential in the yeast, accounting for ~ 43% of essential genes. As expected, essential PPIs are evolutionarily more conserved than nonessential PPIs. Considering the role of essential PPIs in determining gene essentiality, we find the yeast PPI network functionally more robust than random networks, yet far less robust than the potential optimum. These and other findings provide new perspectives on the biological relevance of network structure and robustness.
Journal ArticleDOI
High-Betweenness Proteins in the Yeast Protein Interaction Network
TL;DR: It is found that proteins with high betweenness are more likely to be essential and that evolutionary age of proteins is positively correlated with betweenness, which suggests the existence of some modular organization of the network, and that the high-betweenness, low-connectivity proteins may act as important links between these modules.