Glycogen synthase kinase‐3 regulates mouse oocyte homologue segregation

Wang, Xia; Liu, Xiao-Tie; Dunn, Rodney L.; Ohl, Dana A.; Smith, Gary D.

doi:10.1002/mrd.10213

Cited by 28 publications

(25 citation statements)

References 51 publications

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“…However, despite the fact that both GSK3 inhibitors inhibited GSK3 activity, the effects on embryo development were divergent; LiCl decreased the proportion of zygotes reaching the blastocyst stage, while CT99021 increased development. One of the mechanisms proposed for the actions of lithium in Xenopus embryos and bovine and mouse oocytes is through the direct inhibition of GSK3B (Klein & Melton 1996, Hedgepeth et al 1997, Wang et al 2003, Uzbekova et al 2009). However, lithium also caused a significant decrease in the phosphorylation of GSK3A and GSK3B, indicating activation of the protein.…”

Section: Discussionmentioning

confidence: 99%

Identification and regulation of glycogen synthase kinase-3 during bovine embryo development

Aparicio¹,

García-Herreros²,

Fair³

et al. 2010

Reproduction

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The aim of this study was to examine the presence and regulation of glycogen synthase kinase-3a (GSK3A) and GSK-3b (GSK3B) in bovine embryos and their possible roles in embryo development. Our results show that GSK3A and GSK3B are present in bovine embryos at the two-cell stage to the hatched blastocyst stage. Bovine embryo development was associated with an increase in the phosphorylation of both isoforms, being statistically significant at blastocyst and hatched blastocyst stages, compared with earlier stages. Inhibition of GSK3 with CT99021 (3 mM) resulted in a significant increase in the percentage and quality of blastocysts, while inhibition of GSK3 with lithium chloride (LiCl; 20 mM) significantly reduced at the proportion of eight-cell embryos on day 3 and inhibited blastocyst formation. The use of LY294002 (10 mM), a specific inhibitor of phosphatidylinositol-3 kinase, also produced a significant decrease in embryo development. In addition, treatment with LiCl and LY294002 produced a significant decrease in the serine phosphorylation of both isoforms of GSK3. Finally, CT99021 and LiCl reduced the phosphorylation of b-catenin on Ser45 in two-cell embryos, while LY294002 increased it. Despite the fact that LiCl inhibited GSK3 activity, as demonstrated by b-catenin phosphorylation, its effects on the bovine embryo could be mediated through other signaling pathways leading finally to a decrease in the phosphorylation of GSK3 and a reduction in embryo development. Therefore, in conclusion, GSK3A/B serine phosphorylation was positively correlated with embryo development, indicating the importance of an accurate regulation of GSK3 activity during developmental stages to achieve normal bovine embryo development.

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Section: Discussionmentioning

confidence: 99%

Identification and regulation of glycogen synthase kinase-3 during bovine embryo development

Aparicio¹,

García-Herreros²,

Fair³

et al. 2010

Reproduction

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“…Effectively, the expression of GSK3A and GSK3B varied in different tissues of mammals with a poor correlation between mRNA and protein levels, reflecting the differential regulation of transcription and translation for these highly similar kinases (Woodgett 1990, Lau et al 1999. GSK3A mRNA was not detected in mice oocytes and embryos, whereas both GSK3A and GSK3B proteins were evidenced and differentially phosphorylated (Wang et al 2003, Acevedo et al 2007b. GSK3 is involved in the regulation of transcription by phosphorylation or destabilisation of transcriptional factors, maintaining them in an inactive state under basal conditions .…”

Section: Gsk3b Expression In Bovine Oocytes and Surrounding Folliculamentioning

confidence: 99%

“…Cystic ovarian follicles are also a major cause of reproductive failure in high-lactating dairy cattle (Vanholder et al 2006), which could also affect the oocyte quality (Bartolome et al 2002). In vertebrates, GSK3 was shown to be involved in regulation of meiosis progression in frog oocytes (Fisher et al 1999, Sarkissian et al 2004) and in both male and female germ cells in mice (Guo et al 2003, Wang et al 2003, Liu et al 2007. In mice, GSK3 is also involved in the regulation of chromatin segregation and cytokinesis in early embryo (Acevedo et al 2007b).…”

Section: Introductionmentioning

confidence: 99%

Glycogen synthase kinase 3B in bovine oocytes and granulosa cells: possible involvement in meiosis during in vitro maturation

Uzbekova¹,

Salhab²,

Perreau³

et al. 2009

Reproduction

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Glycogen synthase kinase 3 (GSK3) regulates cellular metabolism and cell cycle via different signalling pathways. In response to insulin and growth factors GSK3 is serine-phosphorylated and inactivated. We analysed GSK3B expression and activation in bovine cumulus cells (CC) and oocytes at different meiotic stages in vitro in parallel with MAP kinases ERK (MAPK3/MAPK1) and p38 (MAPK14). GSK3B localised to cytoplasm in granulosa cells and in oocytes throughout folliculogenesis. In mature metaphase-II (MII) oocytes, GSK3B was concentrated to the region of midzone between the oocyte and the first polar body, as well as active phospho-Thr Aurora A kinase (AURKA). During in vitro maturation (IVM), in oocytes, phospho-Ser 9 -GSK3B level increased as well as phospho-MAPK3/MAPK1, while phospho-MAPK14 decreased. In CC, phospho-MAPK14 increased upon germinal vesicle breakdown (GVBD)/metaphase-I (MI) and then decreased during transition to MII. Administration of inhibitors of GSK3 activity (lithium chloride or 2 0 Z,3 0 E -6-bromoindirubin-3 0 -oxime) rapidly increased phospho-Ser 9 -GSK3B, and led to transient decrease of phospho-MAPK3/MAPK1 and to durable enhancing of phospho-MAPK14 in granulosa primary cell culture. GSK3 inhibitors during IVM diminished cumulus expansion and delayed meiotic progression. In cumulus, phospho-MAPK14 level was significantly higher in the presence of inhibitors, comparing with control, through the time of MI/MII transition. In oocytes, phospho-GSK3B was increased and phospho-MAPK3/MAPK1 was decreased before GVBD and oocytes were mainly arrested at MI. Therefore, GSK3B might regulate oocyte meiosis, notably MI/MII transition being the part of MAPK3/1 and MAPK14 pathways in oocytes and CC. GSK3B might be also involved in the local activation of AURKA that controls this transition.

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“…No difference in spindle morphology was detected between 2,000 ng/ml and 5.5 ng/ml FSH groups (45.0% versus 50.0%) [13]. The exact mechanism by which FSH induces aneuploidy remains unclear, although several possibilities have been proposed, including oocyte susceptibility to environmental factors during the first meiosis [28][29][30], effects of FSH on microtubules [31,32], and enhanced meiotic resumption of abnormal oocytes which may be otherwise destined for atresia.…”

Section: Discussionmentioning

confidence: 97%

Differentially expressed micoRNAs in human oocytes

Wang

Ding

et al. 2011

J Assist Reprod Genet

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Purpose To identify differentially expressed microRNAs (miRNAs) and expression patterns of specific miRNAs during meiosis in human oocytes. Materials and methods To identify differentially expressed miRNAs, GV oocytes and MII oocytes matured at conventional FSH levels (5.5 ng/ml) were analyzed by miRNA microarray. Real-time RT-PCR was used to confirm the changed miRNAs. To validate the dynamic changes of miRNAs from GV to MII stages, oocytes were divided into four groups (#1-4), corresponding to GVoocytes, MI oocytes, MII oocytes matured in conventional FSH level and MII oocytes matured in high FSH level (2,000 ng/ml) respectively. Results Compared with GVoocytes, MII oocytes exhibited up-regulation of 4 miRNAs (hsa-miR-193a-5p, hsa-miR-297, hsa-miR-625 and hsa-miR-602), and down-regulation of 11 miRNAs (hsa-miR-888*, hsa-miR-212, hsa-miR-662, hsa-miR-299-5p, hsa-miR-339-5p, hsa-miR-20a, hsa-miR-486-5p, hsa-miR-141*, hsa-miR-768-5p, hsa-miR-376a and hsa-miR-15a). RT-PCR analysis of hsa-miR-15a and hsamiR-20a expression revealed concordant dynamic changes in oocytes from group 1 to group 4. Conclusion(s) Specific miRNAs in human oocytes had dynamic changes during meiosis. High-concentration FSH in IVM medium led to reverse effect on the expression of hsa-miR-15a and hsa-miR-20a.Keywords miRNA . Oocytes . In vitro maturation . qRT-PCR Oocyte growth and early development requires large amounts of maternally-derived transcripts which are subjected to massive destruction as oocytes mature. Of the estimated 85 pg of polyadenylated mRNAs present in a germinal vesicle (GV)-stage mouse oocyte, 50 pg of mRNAs are degraded during oocyte maturation [1]. Furthermore, transcript degradation is highly selective, primarily affecting genes involved in processes associated with meiotic arrest at the GV-stage and progression of oocyte maturation, such as oxidative phosphorylation, energy production, protein synthesis and metabolism [2]. On the other hand, up-regulation of a number of transcripts during oocyte maturation was also observed in mice, cattle, and humans in recent years [3][4][5].miRNAs are a family of small non-coding RNAs that play important regulatory roles in gene expression. Specifically, miRNA-mediated translational regulation involves cleavage of messenger RNAs or repression of mRNA translation [6]. It has been estimated that 30% or more of human mRNAs are regulated by miRNAs [7]. Likewise, miRNAs may also play an important role in modulating gene expression in oocytes [8].Dynamic changes in miRNA expression during oogenesis were first revealed by a real-time PCR-based miRNA expression profiling method in single mouse oocytes [8]. A Yan-Wen Xu and Bin Wang contributed equally to this study. Capsule Differentially expressed miRNAs in the human oocytes between GV and MII stages were identified by miRNA microarrays. Dynamic changes of miR-15a, hsa-miR-20a, and miR-602 during meiosis were validated by qRT-PCR.

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Glycogen synthase kinase‐3 regulates mouse oocyte homologue segregation

Cited by 28 publications

References 51 publications

Identification and regulation of glycogen synthase kinase-3 during bovine embryo development

Identification and regulation of glycogen synthase kinase-3 during bovine embryo development

Glycogen synthase kinase 3B in bovine oocytes and granulosa cells: possible involvement in meiosis during in vitro maturation

Differentially expressed micoRNAs in human oocytes

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