Insulin Signaling in Mouse Oocytes1

Acevedo, Nicole; Ding, Jun; Smith, Gary D.

doi:10.1095/biolreprod.107.060152

Cited by 60 publications

(57 citation statements)

References 59 publications

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“…However, 19 h insulin treatment of denuded oocytes did not alter phosphorylation of GSK3A or B. The effect of insulin treatment on other enzymes in the insulin signaling pathway in oocytes or cumulus cells is unknown [102]. The IGF-1 knockout mice have decreased granulosa cell proliferation and decreased GLUT1 [89,104], similar to results observed in blastocysts following PI3K inhibition [98].…”

Section: Insulinmentioning

confidence: 61%

“…Other studies in COCs showed that inhibition of the PI3K pathway reduced glucose uptake in response to FSH, but did not investigate the role of insulin [86]. The terminal enzyme in insulin signaling, glycogen synthase kinase 3A/B (GSK3A/B) is present in denuded oocytes [102]. However, 19 h insulin treatment of denuded oocytes did not alter phosphorylation of GSK3A or B.…”

Section: Insulinmentioning

confidence: 98%

“…The ovary is a target organ for insulin [21] and both the oocyte and surrounding cumulus cells of mice contain the insulin receptor [102]. In humans the insulin and IGF-1 receptor have been found in the granulosa, theca, and ovarian stroma [21].…”

Section: Insulinmentioning

confidence: 99%

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The impact of obesity on egg quality

Purcell

Moley

2011

J Assist Reprod Genet

136

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Obesity in women is a concern in many countries. This causes numerous health issues; however, this review focuses on the impact of obesity on women's reproduction, and in particular the oocyte. Data from infertility clinics and experimental animal models that address the effects of obesity are presented. Bidirectional communication and metabolic support from the surrounding cumulus cells are critical for oocyte development, and the impact of obesity on these cells is also addressed. Both oocyte maturation and metabolism are impaired due to obesity, negatively impacting further development. In addition to reproductive hormones, obesity induced elevations in insulin, glucose, or free fatty acids, and changes in adipokines appear to impact the developmental competence of the oocyte. The data indicate that any one of these hormones or metabolites can impair oocyte developmental competence in vivo, and the combination of all of these factors and their interactions are the subject of ongoing investigations.

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Section: Insulinmentioning

confidence: 61%

Section: Insulinmentioning

confidence: 98%

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The impact of obesity on egg quality

Purcell

Moley

2011

J Assist Reprod Genet

136

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“…The involvement of different MAPKs in oocyte meiotic progression was reported also in mice, where levels of MAPK14, MAPK3/MAPK1 and JNK kinases' activities were shown to vary with the stage of oocyte maturation (Baatout et al 2007). Members of insulin signalling cascade, including AKT and GSK3 were shown to play important roles in mice oocyte meiosis completion (Acevedo et al 2007a). In addition, GSK3 was reported as the only kinase capable to phosphorylate Aurora-A in Xenopus oocytes (Sarkissian et al 2004).…”

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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“…In mammals, insulin signaling affects oocyte maturation and fertilization. 1,2 Mutations in the insulin signaling pathway in C. elegans can lengthen life span but reduce fertility. 3,4 Improper insulin signaling in Drosophila leads to reduced body size and female sterility.…”

mentioning

confidence: 99%

Role of the insulin/Tor signaling network in starvation-induced programmed cell death in Drosophila oogenesis

Pritchett

McCall

2012

Cell Death Differ

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Amino-acid starvation leads to an inhibition of cellular proliferation and the induction of programmed cell death (PCD) in the Drosophila ovary. Disruption of insulin signaling has been shown to inhibit the progression of oogenesis, but it is unclear whether this phenotype mimics starvation. Here, we investigate whether the insulin-mediated phosphoinositide kinase-3 pathway regulates PCD in mid oogenesis. We reasoned that under well-fed conditions, disruption of positive components of the insulin signaling pathway within the germline would mimic starvation and produce degenerating egg chambers. Surprisingly, mutants did not mimic starvation but instead produced many abnormal egg chambers in which the somatic follicle cells disappeared and the germline persisted. These abnormal egg chambers did not show an induction of caspases and lysosomes like that observed in wild-type (WT) degenerating egg chambers. Egg chambers from insulin signaling mutants were resistant to starvation-induced PCD, indicating that a complete block in insulin-signaling prevents the proper response to starvation. However, target of rapamycin (Tor) mutants did show a phenotype that mimicked WT starvation-induced PCD, indicating an insulin independent regulation of PCD via Tor signaling. These results suggest that inhibition of the insulin signaling pathway is not sufficient to regulate starvation-induced PCD in mid oogenesis. Furthermore, starvation-induced PCD is regulated by Tor signaling converging with the canonical insulin signaling pathway. The insulin-mediated class I phosphoinositide kinase-3 (PI3K) pathway is a highly conserved nutrient-sensing pathway in diverse organisms. In mammals, insulin signaling affects oocyte maturation and fertilization. 1,2 Mutations in the insulin signaling pathway in C. elegans can lengthen life span but reduce fertility. 3,4 Improper insulin signaling in Drosophila leads to reduced body size and female sterility. 5 Thus, insulin signaling is essential for reproduction in diverse organisms, but how this pathway regulates fertility is not fully understood.Proper nutrition during Drosophila oogenesis is critical for egg chamber production. 6-8 Depriving flies of yeast as a protein source leads to programmed cell death (PCD) at two stages: early oogenesis in the germarium and mid oogenesis during stages 7-9. 7 Egg chambers undergoing PCD during mid oogenesis are characterized by nuclear condensation and fragmentation of germline-derived nurse cells (NCs), engulfment by somatic follicle cells (FCs), and ultimately FC death. 5 During PCD in mid oogenesis, dying NCs show characteristics of both apoptotic and autophagic PCD. 5 The effector caspase Death caspase-1 (Dcp-1) is essential for germline PCD in mid oogenesis. dcp-1 mutants that have been starved display mid-stage egg chambers that have a persistence of uncondensed NC nuclei but an absence of FCs. 5 This phenotype indicates that the dcp-1 mutant germline is unable to die in response to starvation, although the FCs respond and undergo PCD. dcp-1 mutants ...

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Insulin Signaling in Mouse Oocytes1

Cited by 60 publications

References 59 publications

The impact of obesity on egg quality

The impact of obesity on egg quality

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

Role of the insulin/Tor signaling network in starvation-induced programmed cell death in Drosophila oogenesis

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