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532339 occurrences (No.23 in the rank) during 5 years in the PubMed. [no cache] 500 found

167) Studies on bovine oocytes have revealed that the activation of adenosine monophosphate activated protein kinase (AMPK) by millimolar concentrations of metformin controls nuclear maturation.

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PMID:23870192 DOI:10.1017/S0967199413000300

2015 Zygote (Cambridge, England)

* 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.

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(2)47 null	(15)7 should	(28)3 for	(41)2 indicated
(3)32 of	(16)6 is	(29)3 however,	(42)2 investigating
(4)26 are	(17)6 we	(30)3 performed	(43)2 involving
(5)26 on	(18)5 suggest	(31)3 reported	(44)2 it
(6)19 in	(19)5 the	(32)3 since	(45)2 or
(7)17 were	(20)4 as	(33)3 which	(46)2 provide
(8)16 and	(21)4 demonstrated	(34)2 about	(47)2 published
(9)15 to	(22)4 evaluating	(35)2 also	(48)2 regarding
(10)10 showed	(23)4 from	(36)2 can	(49)2 targeting
(11)8 revealed	(24)4 indicate	(37)2 concerning	(50)2 tested
(12)8 that	(25)4 show	(38)2 demonstrating	(51)2 used
(13)8 using	(26)3 based	(39)2 has	(52)2 was

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--- WordNet output for studies --- Overview of noun study The noun study has 10 senses (first 8 from tagged texts) 1. (90) survey, study -- (a detailed critical inspection) 2. (17) study, work -- (applying the mind to learning and understanding a subject (especially by reading); "mastering a second language requires a lot of work"; "no schools offer graduate study in interior design") 3. (6) report, study, written report -- (a written document describing the findings of some individual or group; "this accords with the recent study by Hill and Dale") 4. (6) study -- (a state of deep mental absorption; "she is in a deep study") 5. (6) study -- (a room used for reading and writing and studying; "he knocked lightly on the closed door of the study") 6. (3) discipline, subject, subject area, subject field, field, field of study, study, bailiwick -- (a branch of knowledge; "in what discipline is his doctorate?"; "teachers should be well trained in their subject"; "anthropology is the study of human beings") 7. (2) sketch, study -- (preliminary drawing for later elaboration; "he made several studies before starting to paint") 8. (1) cogitation, study -- (attentive consideration and meditation; "after much cogitation he rejected the offer") 9. study -- (someone who memorizes quickly and easily (as the lines for a part in a play); "he is a quick study") 10. study -- (a composition intended to develop one aspect of the performer's technique; "a study in spiccato bowing") Overview of verb study The verb study has 6 senses (first 6 from tagged texts) 1. (73) analyze, analyse, study, examine, canvass, canvas -- (consider in detail and subject to an analysis in order to discover essential features or meaning; "analyze a sonnet by Shakespeare"; "analyze the evidence in a criminal trial"; "analyze your real motives") 2. (17) study -- (be a student; follow a course of study; be enrolled at an institute of learning) 3. (15) study, consider -- (give careful consideration to; "consider the possibility of moving") 4. (13) learn, study, read, take -- (be a student of a certain subject; "She is reading for the bar exam") 5. (5) study, hit the books -- (learn by reading books; "He is studying geology in his room"; "I have an exam next week; I must hit the books now") 6. (2) study, meditate, contemplate -- (think intently and at length, as for spiritual purposes; "He is meditating in his study") --- WordNet end ---