Expression patterns of sirtuin genes in porcine preimplantation embryos and effects of sirtuin inhibitors on in vitro embryonic development after parthenogenetic activation and in vitro fertilization

Kwak, Seong-Sung; Cheong, Seung-A; Yoon, Jong Hwan; Jeon, Yubyeol; Hyun, Sang‐Hwan

doi:10.1016/j.theriogenology.2012.07.006

Cited by 36 publications

(37 citation statements)

References 43 publications

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“…Gene expression of the the Class III HDACs, SIRT2, which is not inhibited by Scriptaid, SAHA, or ISAHA, was significantly increased at the blastoycyst stage in HDACitreated embryos. SIRT1 was not affected by treatment, but highly expressed in all of the blastocyst-stage embryos, which is in contrast to a previous report that showed SIRT 1-3 were expressed at a low level in blastocyst-stage embryos when analyzed by real-time PCR (Kwak et al, 2012). We did not observe a significant change in any transcripts associated with histone acetyltransferase activity (HAT1 or CITED1), DNA methyltransferases (DNMT1 or DNMT3A), or Tet methylcytosine dioxygenases (TET1, TET2, and TET3).…”

Section: Discussioncontrasting

confidence: 99%

Transcriptome Analysis of PigIn Vivo,In Vitro–Fertilized, and Nuclear Transfer Blastocyst-Stage Embryos Treated with Histone Deacetylase Inhibitors Postfusion and Activation Reveals Changes in the Lysosomal Pathway

Whitworth

Mao

Lee

et al. 2015

Cellular Reprogramming

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Genetically modified pigs are commonly created via somatic cell nuclear transfer (SCNT). Treatment of reconstructed embryos with histone deacetylase inhibitors (HDACi) immediately after activation improves cloning efficiency. The objective of this experiment was to evaluate the transcriptome of SCNT embryos treated with suberoylanilide hydroxamic acid (SAHA), 4-iodo-SAHA (ISAHA), or Scriptaid as compared to untreated SCNT, in vitro-fertilized (IVF), and in vivo (IVV) blastocyst-stage embryos. SAHA (10 μM) had the highest level of blastocyst development at 43.9%, and all treatments except 10 μM ISAHA had the same percentage of blastocyst development as Scriptaid (p<0.05). Two treatments, 1.0 μM ISAHA and 1.0 μM SAHA, had higher mean cell number than No HDACi treatment (p<0.021). Embryo transfers performed with 10 μM SAHA- and 1 μM ISAHA-treated embryos resulted in the birth of healthy piglets. GenBank accession numbers from up- and downregulated transcripts were loaded into the Database for Annotation, Visualization and Integrated Discovery to identify enriched biological themes. HDACi treatment yielded the highest enrichment for transcripts within the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway, lysosome. The mean intensity of LysoTracker was lower in IVV embryos compared to IVF and SCNT embryos (p<0.0001). SAHA and ISAHA can successfully be used to create healthy piglets from SCNT.

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Section: Discussioncontrasting

confidence: 99%

Transcriptome Analysis of PigIn Vivo,In Vitro–Fertilized, and Nuclear Transfer Blastocyst-Stage Embryos Treated with Histone Deacetylase Inhibitors Postfusion and Activation Reveals Changes in the Lysosomal Pathway

Whitworth

Mao

Lee

et al. 2015

Cellular Reprogramming

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“…Sirt1 protein is readily detected in mouse zygotes, 2-cell embryos and blastocysts (McBurney et al 2003). mRNA for Sirt1-7 is readily detected in mouse oocytes and zygotes, but expression is downregulated from the 2-cell stage onwards, with only minimal Sirt1, Sirt2 and Sirt7 detected at the blastocyst stage (Kawamura et al 2010), a pattern similarly observed in pig oocytes and embryos for SIRT1-3 (Kwak et al 2012b). Inhibition of sirtuins during mouse preimplantation development with nicotinamide, sirtinol or N-(2-aminophenyl)-N 0 -phenyloctanediamide, decreases blastocyst development associated with increased ROS production (Kawamura et al 2010).…”

Section: Sirts: Linking Nutrient Use With Epigeneticsmentioning

confidence: 65%

Blastocyst metabolism

Gardner¹,

Harvey²

2015

Reprod. Fertil. Dev.

130

108

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The mammalian blastocyst exhibits an idiosyncratic metabolism, reflecting its unique physiology and its ability to undergo implantation. Glucose is the primary nutrient of the blastocyst, and is metabolised both oxidatively and through aerobic glycolysis. The production of significant quantities of lactate by the blastocyst reflects specific metabolic requirements and mitochondrial regulation; it is further proposed that lactate production serves to facilitate several key functions during implantation, including biosynthesis, endometrial tissue breakdown, the promotion of new blood vessel formation and induction of local immune-modulation of the uterine environment. Nutrient availability, oxygen concentration and the redox state of the blastocyst tightly regulate the relative activities of specific metabolic pathways. Notably, a loss of metabolic normality is associated with a reduction in implantation potential and subsequent fetal development. Even a transient metabolic stress at the blastocyst stage culminates in low fetal weights after transfer. Further, it is evident that there are differences between male and female embryos, with female embryos being characterised by higher glucose consumption and differences in their amino acid turnover, reflecting the presence of two active X-chromosomes before implantation, which results in differences in the proteomes between the sexes. In addition to the role of Hypoxia-Inducible Factors, the signalling pathways involved in regulating blastocyst metabolism are currently under intense analysis, with the roles of sirtuins, mTOR, AMP-activated protein kinase and specific amino acids being scrutinised. It is evident that blastocyst metabolism regulates more than the production of ATP; rather, it is apparent that metabolites and cofactors are important regulators of the epigenome, putting metabolism at centre stage when considering the interactions of the blastocyst with its environment.

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“…Experiments in Sirt3-knockdown embryos have revealed that manipulation of SIRT3 activity results in changes of gene expression and ROS-p53 pathway. These observations in the mouse have been confirmed in porcine embryos where SIRT3 has been found to regulate early embryo development by modulating essential gene expressions in concert with SIRT1 and SIRT3 [ 112 ]. Thus targeting SIRT3 might be a potential measure for promoting positive outcome in IVF by improving developmental potential of early embryos.…”

Section: Sirtuins and Female Reproductive Functionsmentioning

confidence: 82%

Sirtuin Functions in Female Fertility: Possible Role in Oxidative Stress and Aging

Tatone

Emidio

Vitti

et al. 2015

Oxidative Medicine and Cellular Longevity

135

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In search for strategies aimed at preventing oxidative threat to female fertility, a possible role of sirtuins has emerged. Sirtuins (silent information regulator 2 (Sir2) proteins), NAD+ dependent enzymes with deacetylase and/or mono-ADP-ribosyltransferase activity, are emerging as key antiaging molecules and regulators in many diseases. Recently, a crucial role for SIRT1 and SIRT3, the main components of sirtuin family, as sensors and guardians of the redox state in oocytes, granulosa cells, and early embryos has emerged. In this context, the aim of the present review is to summarize current knowledge from research papers on the role of sirtuins in female fertility with particular emphasis on the impairment of SIRT1 signalling with oocyte aging. On this basis, the authors wish to build up a framework to promote research on the possible role of sirtuins as targets for future strategies for female fertility preservation.

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Expression patterns of sirtuin genes in porcine preimplantation embryos and effects of sirtuin inhibitors on in vitro embryonic development after parthenogenetic activation and in vitro fertilization

Cited by 36 publications

References 43 publications

Transcriptome Analysis of PigIn Vivo,In Vitro–Fertilized, and Nuclear Transfer Blastocyst-Stage Embryos Treated with Histone Deacetylase Inhibitors Postfusion and Activation Reveals Changes in the Lysosomal Pathway

Transcriptome Analysis of PigIn Vivo,In Vitro–Fertilized, and Nuclear Transfer Blastocyst-Stage Embryos Treated with Histone Deacetylase Inhibitors Postfusion and Activation Reveals Changes in the Lysosomal Pathway

Blastocyst metabolism

Sirtuin Functions in Female Fertility: Possible Role in Oxidative Stress and Aging

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