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468) Metformin (10 μM) either throughout IVP or during IVF only, increased AMPK-induced PhosphoS1387-TSC2 immunoreactivity (P < 0.01) and this increase corresponded to the total TSC2 protein levels expressed in cells.
* Effects of metformin on fertilisation of bovine oocytes and early embryo development: possible involvement of AMPK3-mediated TSC2 activation.
- Studies on bovine oocytes have revealed that the activation of adenosine monophosphate activated protein kinase (AMPK) by millimolar concentrations of metformin controls nuclear maturation. Tuberous sclerosis complex 2 (TSC2) has been identified as a downstream target of AMPK. The objective of this study was to investigate the effects of addition of low concentrations of metformin (1 nM to 10 μM) on the percentage of cultured cumulus-oocyte complexes (COC) giving rise to cleavage-stage embryos and AMPK-mediated TSC2 activation. Metformin was supplemented either throughout in vitro embryo production (IVP) or only during in vitro fertilization (IVF). COC were matured in vitro, inseminated, and presumptive zygotes cultured for a further 72 h post insemination before the percentage of COC that gave rise to zygotes and early embryo development was assessed. The presence of TSC2 in bovine embryos and its possible AMPK-induced activation were assessed by immunocytochemistry. Metformin had a dose-dependent effect on the numbers of cultured COC that gave rise to embryos. Drug treatment either throughout IVP or only during IVF decreased the percentage of ≥ 8-cell embryos (1 μM, P < 0.05; 10 μM, P < 0.01; and 0.1 μM, 10 μM, P < 0.01, respectively) and increased the percentage of 2-cell embryos (10 μM, P < 0.01 and P < 0.05 respectively). The percentage of cultured COC that gave rise to zygotes was not affected by metformin. TSC2 is expressed in early embryos. Metformin (10 μM) either throughout IVP or during IVF only, increased AMPK-induced PhosphoS1387-TSC2 immunoreactivity (P < 0.01) and this increase corresponded to the total TSC2 protein levels expressed in cells. Our results suggest that there is a dose-dependent negative effect of metformin on the ability of oocytes to cleave following insemination, possibly mediated through an AMPK-induced activation of TSC2.
Overview of noun level
The noun level has 8 senses (first 6 from tagged texts)
1. (69) degree, grade, level -- (a position on a scale of intensity or amount or quality; "a
moderate grade of intelligence"; "a high level of care is required"; "it is all a matter of degree")
2. (22) grade, level, tier -- (a relative position or degree of value in a graded group; "lumber of
the highest grade")
3. (15) degree, level, stage, point -- (a specific identifiable position in a continuum or series or
especially in a process; "a remarkable degree of frankness"; "at what stage are the social
sciences?")
4. (5) level -- (height above ground; "the water reached ankle level"; "the pictures were at the
same level")
5. (1) level, spirit level -- (indicator that establishes the horizontal when a bubble is centered
in a tube of liquid)
6. (1) horizontal surface, level -- (a flat surface at right angles to a plumb line; "park the car
on the level")
7. level, layer, stratum -- (an abstract place usually conceived as having depth; "a good actor
communicates on several levels"; "a simile has at least two layers of meaning"; "the mind functions
on many strata simultaneously")
8. floor, level, storey, story -- (a structure consisting of a room or set of rooms at a single
position along a vertical scale; "what level is the office on?")
Overview of verb level
The verb level has 6 senses (first 3 from tagged texts)
1. (4) level -- (aim at; "level criticism or charges at somebody")
2. (1) level, raze, rase, dismantle, tear down, take down, pull down -- (tear down so as to make
flat with the ground; "The building was levelled")
3. (1) flush, level, even out, even -- (make level or straight; "level the ground")
4. charge, level, point -- (direct into a position for use; "point a gun"; "He charged his weapon at
me")
5. level -- (talk frankly with; lay it on the line; "I have to level with you")
6. level, level off -- (become level or even; "The ground levelled off")
--- WordNet end ---