Increases in phosphorylation of SAPK/JNK and p38MAPK correlate negatively with mouse embryo development after culture in different media

Wang, Yingchun; Puscheck, Elizabeth E.; Lewis, Jennifer; Trostinskaia, Anna; Wang, Fangfei; Rappolee, Daniel A.

doi:10.1016/j.fertnstert.2004.08.038

Cited by 69 publications

(105 citation statements)

References 52 publications

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“…Embryos showing signs of fragmentation and delayed or accelerated development were discarded. In all studies, embryos were equilibrated for at least 1 h in lowest-stress KSOM AA [54] and stressed with the stimulus dose for the time period indicated. KSOM AA was 260-270 mOsmol, increasing 1.7-fold to 498 mOsmol with the addition of 200 mM sorbitol.…”

Section: Embryo Culture and Treatmentmentioning

confidence: 99%

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Bolnick

Abdulhasan

Kilburn

et al. 2016

J Assist Reprod Genet

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Purpose The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3, 3′-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development. Methods The methods used were as follows: culture post-thaw mouse zygotes to the two-cell embryo stage and test effects after 1-h AMPK agonists' (e.g., Met, Asa, BR-DIM, control hyperosmotic stress) exposure on AMPK-dependent loss of Oct4 and/or Rex1 nuclear potency factors, confirm AMPK dependence by reversing potency loss in two-cell-stage embryos with AMPK inhibitor compound C (CC), test whether Met + Asa (i.e., co-added) or DS BR-DIM decreases development of two-cell to blastocyst stage in an AMPK-dependent (CCsensitive) manner, and evaluate the level of Rex1 and Oct4 nuclear fluorescence in two-cell-stage embryos and rate of two-cell-stage embryo development to blastocysts. Result(s) Met, Asa, BR-DIM, or hyperosmotic sorbitol stress induces rapid~50-85 % Rex1 and/or Oct4 protein loss in twocell embryos. This loss is~60-90 % reversible by co-culture with AMPK inhibitor CC. Embryo development from twocell to blastocyst stage is decreased in culture with either Met + Asa or BR-DIM, and this is either >90 or~60 % reversible with CC, respectively. Conclusion These experimental designs here showed that Met-, Asa-, BR-DIM-, or sorbitol stress-induced rapid potency loss in two-cell embryos is AMPK dependent as suggested by inhibition of Rex1 and/or Oct4 protein loss with an AMPK inhibitor. The DS BR-DIM or fertility drugs (e.g., Met + Asa)Capsule Drugs metformin and aspirin and diet supplement BR-DIM cause AMPK-dependent potency loss and decrease embryonic development from two-cell to blastocyst stage. Reprod Genet (2016) 33:1027-1039 DOI 10.1007 that are used to enhance maternal metabolism to support fertility can also chronically slow embryo growth and block development in an AMPK-dependent manner.

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Section: Embryo Culture and Treatmentmentioning

confidence: 99%

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Bolnick

Abdulhasan

Kilburn

et al. 2016

J Assist Reprod Genet

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“…Female MF-1 mice (4-5 weeks old; Harlan Sprague Dawley) were super-ovulated, and their embryos were obtained as described previously [38,39] or their unfertilized oocytes were collected 6 h after human chorionic gonadotropin (hCG) (germinal vesicle breakdown-GVDB-stage) or 15 h after hCG (meiosis or MII stage). Animal use protocols were approved by the Wayne State University Animal Investigation Committee.…”

Section: Collection and Culture Conditions For Mouse Embryosmentioning

confidence: 99%

Stress Induces AMPK-Dependent Loss of Potency Factors Id2 and Cdx2 in Early Embryos and Stem Cells

Xie

Awonuga

Liu

et al. 2013

Stem Cells and Development

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The AMP-activated protein kinase (AMPK) mediates rapid, stress-induced loss of the inhibitor of differentiation (Id)2 in blastocysts and trophoblast stem cells (TSC), and a lasting differentiation in TSC. However, it is not known if AMPK regulates other potency factors or regulates them before the blastocyst stage. The caudal-related homeodomain protein (Cdx)2 is a regulatory gene for determining TSC, the earliest placental lineage in the preimplantation mouse embryo, but is expressed in the oocyte and in early cleavage stage embryos before TSC arise. We assayed the expression of putative potency-maintaining phosphorylated Cdx2 ser60 in the oocyte, twocell stage embryo, blastocyst, and in TSC. We studied the loss of Cdx2 phospho ser60 expression induced by hyperosmolar stress and its underlying mechanisms. Hyperosmolar stress caused rapid loss of nuclear Cdx2 phospho ser60 and Id2 in the two-cell stage embryo by 0.5 h. Stress-induced Cdx2 phospho ser60 and Id2 loss is reversed by the AMPK inhibitor compound C and is induced by the AMPK agonist 5-amino-1-b-d-ribofuranosyl-imidazole-4-carboxamide in the absence of stress. In the two-cell stage embryo and TSC hyperosmolar, stress caused AMPK-mediated loss of Cdx2 phospho ser60 as detected by immunofluorescence and immunoblot. We propose that AMPK may be the master regulatory enzyme for mediating stress-induced loss of potency as AMPK is also required for stress-induced loss of Id2 in blastocysts and TSC. Since AMPK mediates potency loss in embryos and stem cells it will be important to measure, test mechanisms for, and manage the AMPK function to optimize the stem cell and embryo quality in vitro and in vivo.

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“…Similar effects of p38 MAPK have been observed in embryos, but the data are contradictory. Natale et al [46] observed blockage of development in mouse pre-implantation embryos after inhibition of p38 MAPK, while Wang et al [47] observed the activity of p38 MAPK during in vitro culture of embryos. An increase of active forms of the kinase induces blockage of embryo development.…”

Section: Discussionmentioning

confidence: 99%

The Roles of c-Jun N-terminal Kinase (JNK) and p38 Mitogen-activated Protein Kinase (p38 MAPK) in Aged Pig Oocytes

Petrova

Sedmı́ková

Petr³

et al. 2009

Journal of Reproduction and Development

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Abstract. After reaching metaphase II, in vitro matured oocytes undergo the complex processes referred to as oocyte aging. Under our culture conditions, some aged oocytes remained at the stage of metaphase II, some underwent spontaneous parthenogenetic activation and others underwent cellular death, either through apoptosis (fragmentation) or lysis. We investigated the effect of c-Jun N-terminal kinases (JNK) and p38 Mitogen-activated protein kinase (p38 MAPK) inhibition on pig oocyte aging and the activity of JNK and p38 MAPK during the aging period. Inhibition of JNK protected the oocytes from fragmentation (0% fragmented oocytes under JNK inhibition vs. 26% fragmented oocytes in the control group). Inhibition of p38 MAPK had no effect on fragmentation. Inhibition of JNK also had an influence on spontaneous parthenogenetic activation of aged oocytes. The ratio of activated JNK to total JNK decreased during aging of oocytes. However, exit from MII had no effect on it. The ratio of activated p38 MAPK to total p38 MAPK did not change significantly. The phosphorylated form of JNK is present in fragmented and activated oocytes, while lysed oocytes lack the active form of JNK. Based on our data, we can conclude that JNK plays an active role in fragmentation of pig oocytes and that p38 MAPK is not involved in this process.

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Increases in phosphorylation of SAPK/JNK and p38MAPK correlate negatively with mouse embryo development after culture in different media

Cited by 69 publications

References 52 publications

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Stress Induces AMPK-Dependent Loss of Potency Factors Id2 and Cdx2 in Early Embryos and Stem Cells

The Roles of c-Jun N-terminal Kinase (JNK) and p38 Mitogen-activated Protein Kinase (p38 MAPK) in Aged Pig Oocytes

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