Effect of inhibitors of carbohydrate metabolism on the development of preimplantation mouse embryos

Thomson, Joan L.

doi:10.1016/0014-4827(67)90063-8

Cited by 38 publications

(22 citation statements)

References 13 publications

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“…Whether this is by reversible inhibition of the electron transport chain by NO at the level of cytochrome c oxidase or the persistent inhibition of complex I, via ONOO --mediated oxidation of sulfhydryl groups (Riobo et al, 2001) has not been investigated. However, it is unlikely that NONOate inhibits the electron transport chain completely because ATP production via the Krebs cycle is essential for embryo development (Thomson, 1967;Auerbach and Brinster, 1968). It is plausible that NO produced either by the embryo or by surrounding cells of the reproductive tract is important for the regulation of blastocyst oxygen consumption and that elevated levels of NO in vivo may cause excessive inhibition of oxidative phosphorylation which could compromise development.…”

Section: Discussionmentioning

confidence: 99%

Ca2+-linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo

Manser

Houghton

2006

Journal of Cell Science

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Previous studies have demonstrated a role for the signalling agent nitric oxide in regulating preimplantation embryo development. We have now investigated the biochemical mode of action of nitric oxide in mouse embryos in terms of mitochondrial function and Ca2+ signalling. DETA-NONOate, a nitric oxide donor, decreased day 4 blastocyst cell number and oxygen consumption, consistent with a role for nitric oxide in the inhibition mitochondrial cytochrome c oxidase. Using live cell imaging and the nitric-oxide-sensitive probe DAF-FM diacetate, nitric oxide was detected at all stages of preimplantation development and FRET analysis revealed a proportion of the nitric oxide to be colocalised with mitochondria. This suggests that mitochondria of preimplantation embryos produce nitric oxide to regulate their own oxygen consumption. Inhibiting or uncoupling the electron transport chain induced an increase in nitric oxide and [Ca2+]i as well as disruption of Ca2+ deposits at the plasma membrane, suggesting that mitochondrial disruption can quickly compromise cellular function through Ca2+-stimulated nitric oxide production. A link between antimycin-A-induced apoptosis and nitric oxide signalling is proposed.

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Section: Discussionmentioning

confidence: 99%

Ca2+-linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo

Manser

Houghton

2006

Journal of Cell Science

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“…Reducing the O 2 level to 0.5% prevented even wildtype eight-cell embryos from developing past the morula stage (supplementary material Fig. S3B), because mouse preimplantation development requires some oxygen (Thomson, 1967). However, reducing the oxygen level in embryo cultures to 5% (the level in utero) has been reported to improve preimplantation development (Lawitts and Biggers, 1993; Erbach et al, 1994;Nagy et al, 2003).…”

Section: Tead4mentioning

confidence: 98%

“…In addition, it is likely that the oxygen level in the female reproductive tract is kept hypoxic relative to the atmospheric oxygen level (3-5% versus 21%) (Gardner and Leese, 1990) in order to minimize ROS production. However, some oxygen is required, because OXPHOS is essential for blastocoel development (Thomson, 1967). Thus, embryos must carefully balance energy production, energy usage and ROS production (termed 'energy homeostasis'), because failure to do so results in increased oxidative stress, changes in the intracellular redox potential and impaired biosynthetic potential, all of which are detrimental to development (Harvey et al, 2002;Burton et al, 2003;Dumollard et al, 2007;Van Blerkom, 2009).…”

Section: Introductionmentioning

confidence: 99%

TEAD4 establishes the energy homeostasis essential for blastocoel formation

Kaneko

DePamphilis

2013

Development

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SUMMARYIt has been suggested that during mouse preimplantation development, the zygotically expressed transcription factor TEAD4 is essential for specification of the trophectoderm lineage required for producing a blastocyst. Here we show that blastocysts can form without TEAD4 but that TEAD4 is required to prevent oxidative stress when blastocoel formation is accompanied by increased oxidative phosphorylation that leads to the production of reactive oxygen species (ROS). Both two-cell and eight-cell Tead4 -/− embryos developed into blastocysts when cultured under conditions that alleviate oxidative stress, and Tead4 −/− blastocysts that formed under these conditions expressed trophectoderm-associated genes. Therefore, TEAD4 is not required for specification of the trophectoderm lineage. Once the trophectoderm was specified, Tead4 was not essential for either proliferation or differentiation of trophoblast cells in culture. However, ablation of Tead4 in trophoblast cells resulted in reduced mitochondrial membrane potential. Moreover, Tead4 suppressed ROS in embryos and embryonic fibroblasts. Finally, ectopically expressed TEAD4 protein could localize to the mitochondria as well as to the nucleus, a property not shared by other members of the TEAD family. These results reveal that TEAD4 plays a crucial role in maintaining energy homeostasis during preimplantation development. KEY WORDS:Tead4, Blastocyst, Trophectoderm, Blastocoel, Oxidative stress, Anti-oxidant, Mouse TEAD4 establishes the energy homeostasis essential for blastocoel formation Kotaro J. Kaneko* and Melvin L. DePamphilis DEVELOPMENT 3681 RESEARCH ARTICLE Tead4 and energy homeostasis that are derived from TE (Tanaka et al., 1998;Yagi et al., 2007). The requirement for TEAD4 during preimplantation development is specific for TE, because Tead4 −/− embryos continue to express genes characteristic of the ICM and can produce embryonic stem cells that are derived from the ICM. Thus, Tead4 is the earliest zygotically expressed transcription factor reported to be essential for blastocoel formation and expression of TE-associated genes. Tead4 might also be required for post-implantation development, because it is expressed selectively in extra-embryonic ectoderm as well as in developing placenta (Jacquemin et al., 1996; Jacquemin et al., 1998).In an effort to understand how TEAD4 specifies TE, we made the surprising discovery that Tead4 −/− embryos could form a blastocoel, express TE-associated genes and produce trophoblast giant cells. Therefore, TEAD4 is not essential for specifying the TE lineage. It is, however, essential for blastocoel formation and expansion, but only under conditions that promote oxidative phosphorylation and therefore oxidative stress. By managing oxidative stress in vitro, the requirement for TEAD4 can be bypassed. In fact, analysis of ectopic Tead4 gene expression as well as ablation of Tead4 gene expression suggested that Tead4 is unique among TEAD members in that TEAD4 can localize to mitochondria and affect mitochondrial activi...

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“…The prevailing thought is that reduction in [O 2 ] during culture results in reduction of ROS from oxidative processes, such as OXPHOS; this is supported by the observations that inclusion of antioxidants in the culture media ameliorates oxidative stress and improves development. However, O 2 itself appears to be required for preimplantation development as inhibition of OXPHOS or in vitro culture at 1% O 2 inhibits development (Kaneko & DePamphilis, 2013;Thomson, 1967), although this sensitivity may depend on species (Brison & Leese, 1994;Kane & Buckley, 1977). As mentioned earlier, the need for low levels of O 2 by the cleavage-stage embryos likely reflects their primary reliance on monocarboxylates, amino acids, and/or FAs for energy, which can only generate ATP through OXPHOS, although other oxidative processes such as demethylation of methylated CpG dinucleotides by ten-eleven translocation (TET) proteins (Li & Zhang, 2014) cannot be excluded.…”

Section: Effects Of Oxygen and Amino Acids In The Culture Mediamentioning

confidence: 99%

Metabolism of Preimplantation Embryo Development

Kaneko

2016

Current Topics in Developmental Biology

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Effect of inhibitors of carbohydrate metabolism on the development of preimplantation mouse embryos

Cited by 38 publications

References 13 publications

Ca2+-linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo

Ca2+-linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo

TEAD4 establishes the energy homeostasis essential for blastocoel formation

Metabolism of Preimplantation Embryo Development

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