The Experts below are selected from a list of 18 Experts worldwide ranked by ideXlab platform
Teruhiko Wakayama - One of the best experts on this subject based on the ideXlab platform.
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the histone deacetylase inhibitor scriptaid enhances nascent mrna production and rescues full term development in cloned inbred mice
Reproduction, 2009Co-Authors: Nguyen Van Thuan, Hongthuy Bui, Jinhoi Kim, Takafusa Hikichi, Sayaka Wakayama, Satoshi Kishigami, Eiji Mizutani, Teruhiko WakayamaAbstract:Since the birth of Cumulina, the first Mouse clone produced by somatic cell nuclear transfer (SCNT), the success rate of cloning in mice has been extremely low compared with other species and most of the inbred Mouse strains have never been cloned. Recently, our laboratory has found that treatment of SCNT Mouse embryos with trichostatin A, a histone deacetylase inhibitor (HDACi), improved the full-term development of B6D2F1 Mouse clones significantly. However, this was not effective for the inbred strains. Here, we show for the first time that by treating SCNT embryos with another HDACi, scriptaid, all the important inbred Mouse strains can be cloned, such as C57BL/6, C3H/He, DBA/2, and 129/Sv. Moreover, the success of somatic nuclear reprogramming and cloning efficiency via nuclear transfer technique is clearly linked to the competent de novo synthesis of nascent mRNA in cloned Mouse embryos.
Sugata Hazra - One of the best experts on this subject based on the ideXlab platform.
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the impact of ageing on adipose structure function and vasculature in the B6D2F1 Mouse evidence of significant multisystem dysfunction
The Journal of Physiology, 2014Co-Authors: Anthony J Donato, Grant D Henson, Corey R Hart, Gwenael Layec, Joel D Trinity, Colton R Bramwell, Ryley A Enz, Garrett R Morgan, Kelly D Reihl, Sugata HazraAbstract:The critical influence of the white adipose tissue (WAT) on metabolism is well-appreciated in obesity, but adipose tissue dysfunction as a mechanism underlying age-associated metabolic dysfunction requires elucidation. To explore this possibility, we assessed metabolism and measures of epididymal (e)WAT mitochondria and artery function in young (6.1 ± 0.4 months) and old (29.6 ± 0.2 months) B6D2F1 mice. There were no group differences in average daily oxygen consumption, fasted blood glucose or plasma free fatty acids, but fasted plasma insulin and the homeostatic model assessment of insulin resistance (HOMA-IR%) were higher in the old (∼50-85%, P < 0.05). Tissue mass (P < 0.05) and adipocyte area were lower (∼60%) (P < 0.01) and fibrosis was greater (sevenfold, P < 0.01) in eWAT with older age. The old also exhibited greater liver triglycerides (∼60%, P < 0.05). The mitochondrial respiratory oxygen flux after the addition of glutamate and malate (GM), adenosine diphosphate (d), succinate (S) and octanoyl carnitine (O) were one- to twofold higher in eWAT of old mice (P < 0.05). Despite no change in the respiratory control ratio, substrate control ratios of GMOd/GMd and GMOSd/GMd were ∼30-40% lower in old mice (P < 0.05) and were concomitant with increased nitrotyrosine (P < 0.05) and reduced expression of brown adipose markers (P < 0.05). Ageing reduced vascularity (∼50%, P < 0.01), angiogenic capacity (twofold, P < 0.05) and expression of vascular endothelial growth factor (∼50%, P < 0.05) in eWAT. Finally, endothelium-dependent dilation was lower (P < 0.01) in isolated arteries from eWAT arteries of the old mice. Thus, metabolic dysfunction with advancing age occurs in concert with dysfunction in the adipose tissue characterized by both mitochondrial and arterial dysfunction.
Fernando Rodriguez De Fonseca - One of the best experts on this subject based on the ideXlab platform.
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long term effects of Mouse intracytoplasmic sperm injection with dna fragmented sperm on health and behavior of adult offspring
Biology of Reproduction, 2008Co-Authors: Raul Fernandezgonzalez, Pedro Moreira, Miriam Perezcrespo, Manuel Sanchezmartin, Miguel Angel Ramirez, Eva Pericuesta, Ainhoa Bilbao, Pablo Bermejoalvarez, Juan De Dios Hourcade, Fernando Rodriguez De FonsecaAbstract:Genetic and environmental factors produce different levels of DNA damage in spermatozoa. Usually, DNA-fragmented spermatozoa (DFS) are used with intracytoplasmic sperm injection (ICSI) treatments in human reproduction, and use of DFS is still a matter of concern. The purpose of the present study was to investigate the long-term consequences on development and behavior of mice generated by ICSI with DFS. Using CD1 and B6D2F1 Mouse strains, oocytes were injected with fresh spermatozoa or with frozen-thawed spermatozoa without cryoprotector. This treatment increased the percentage of TUNEL-positive spermatozoa, tail length as measured by comet assay, and loss of telomeres as measured by quantitative PCR. The ICSI-generated embryos were cultured for 24 h in KSOM, and 2-cell embryos were transferred into CD1 females. The DFS reduced both the rate of preimplantation embryo development and number of offspring. Immunofluorescence staining with an antibody against 5-methylcytosine showed a delay of 2 h on the active demethylation of male pronucleus in the embryos produced by ICSI. Moreover, ICSI affected gene transcription and methylation of some epigenetically regulated genes like imprinting, X-linked genes, and retrotransposon genes. At 3 and 12 mo of age, ICSI with DFS-produced animals and in vivofertilized controls were submitted to behavioral tests: locomotor activity (open field), exploratory/anxiety behavior (elevated plus maze, open field), and spatial memory (free-choice exploration paradigm in Y maze). Females produced by ICSI showed increased anxiety, lack of habituation pattern, deficit in shortterm spatial memory, and age-dependent hypolocomotion in the open-field test (P , 0.05). Postnatal weight gain of mice produced by ICSI with fresh or frozen sperm was higher than that of their control counterparts from 16 wk on (P , 0.01). Anatomopathological analysis of animals at 16 mo of age showed some large organs and an increase in pathologies (33% of CD1 females produced with DFS presented some solid tumors in lungs and dermis of back or neck). Moreover, 20% of the B6D2F1 mice generated with DFS died during the first 5 mo of life, with 25% of the surviving animals showing premature aging symptoms, and 70% of the B6D2F1 mice generated with DFS died earlier than controls with different kind of tumors. We propose that depending on the level of DFS, oocytes may partially repair fragmented DNA, producing blastocysts able to implant and produce live offspring. The incomplete repair, however, may lead to long-term pathologies. Our data indicate that use of DFS in ICSI can generate effects that only emerge during later life, such as aberrant growth, premature aging, abnormal behavior, and mesenchymal tumors.
Nguyen Van Thuan - One of the best experts on this subject based on the ideXlab platform.
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the histone deacetylase inhibitor scriptaid enhances nascent mrna production and rescues full term development in cloned inbred mice
Reproduction, 2009Co-Authors: Nguyen Van Thuan, Hongthuy Bui, Jinhoi Kim, Takafusa Hikichi, Sayaka Wakayama, Satoshi Kishigami, Eiji Mizutani, Teruhiko WakayamaAbstract:Since the birth of Cumulina, the first Mouse clone produced by somatic cell nuclear transfer (SCNT), the success rate of cloning in mice has been extremely low compared with other species and most of the inbred Mouse strains have never been cloned. Recently, our laboratory has found that treatment of SCNT Mouse embryos with trichostatin A, a histone deacetylase inhibitor (HDACi), improved the full-term development of B6D2F1 Mouse clones significantly. However, this was not effective for the inbred strains. Here, we show for the first time that by treating SCNT embryos with another HDACi, scriptaid, all the important inbred Mouse strains can be cloned, such as C57BL/6, C3H/He, DBA/2, and 129/Sv. Moreover, the success of somatic nuclear reprogramming and cloning efficiency via nuclear transfer technique is clearly linked to the competent de novo synthesis of nascent mRNA in cloned Mouse embryos.
Anthony J Donato - One of the best experts on this subject based on the ideXlab platform.
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the impact of ageing on adipose structure function and vasculature in the B6D2F1 Mouse evidence of significant multisystem dysfunction
The Journal of Physiology, 2014Co-Authors: Anthony J Donato, Grant D Henson, Corey R Hart, Gwenael Layec, Joel D Trinity, Colton R Bramwell, Ryley A Enz, Garrett R Morgan, Kelly D Reihl, Sugata HazraAbstract:The critical influence of the white adipose tissue (WAT) on metabolism is well-appreciated in obesity, but adipose tissue dysfunction as a mechanism underlying age-associated metabolic dysfunction requires elucidation. To explore this possibility, we assessed metabolism and measures of epididymal (e)WAT mitochondria and artery function in young (6.1 ± 0.4 months) and old (29.6 ± 0.2 months) B6D2F1 mice. There were no group differences in average daily oxygen consumption, fasted blood glucose or plasma free fatty acids, but fasted plasma insulin and the homeostatic model assessment of insulin resistance (HOMA-IR%) were higher in the old (∼50-85%, P < 0.05). Tissue mass (P < 0.05) and adipocyte area were lower (∼60%) (P < 0.01) and fibrosis was greater (sevenfold, P < 0.01) in eWAT with older age. The old also exhibited greater liver triglycerides (∼60%, P < 0.05). The mitochondrial respiratory oxygen flux after the addition of glutamate and malate (GM), adenosine diphosphate (d), succinate (S) and octanoyl carnitine (O) were one- to twofold higher in eWAT of old mice (P < 0.05). Despite no change in the respiratory control ratio, substrate control ratios of GMOd/GMd and GMOSd/GMd were ∼30-40% lower in old mice (P < 0.05) and were concomitant with increased nitrotyrosine (P < 0.05) and reduced expression of brown adipose markers (P < 0.05). Ageing reduced vascularity (∼50%, P < 0.01), angiogenic capacity (twofold, P < 0.05) and expression of vascular endothelial growth factor (∼50%, P < 0.05) in eWAT. Finally, endothelium-dependent dilation was lower (P < 0.01) in isolated arteries from eWAT arteries of the old mice. Thus, metabolic dysfunction with advancing age occurs in concert with dysfunction in the adipose tissue characterized by both mitochondrial and arterial dysfunction.
