Epidermal Growth Factor-Receptor Tyrosine Kinase Activity Regulates Expansion of Porcine Oocyte-Cumulus Cell Complexes In Vitro1

Procházka, Radek; Kaláb, Petr; Nagyová, Eva

doi:10.1095/biolreprod.102.005520

Cited by 80 publications

(60 citation statements)

References 53 publications

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“…EGFR tyrosine kinase and MAPK3/1 activities are crucial for expansion of cumulus cells in different species including the pig (Prochazka et al 2003. Nevertheless, the data of this study indicate that EGFR/MAPK3/1 pathway is not the only pathway controlling gonadotropininduced expression of the expansion-related genes, at least in the in vitro system.…”

Section: Signaling In Pig Cumulus-oocyte Complexesmentioning

confidence: 69%

Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption and cumulus cell expansion in the pig

Procházka¹,

Blaha²,

Němcová³

2012

Reproduction

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To define signaling pathways that drive FSH-and epidermal growth factor (EGF)-like peptide-induced cumulus expansion and oocyte meiotic resumption, in vitro cultured pig cumulus-oocyte complexes were treated with specific protein kinase inhibitors. We found that FSH-induced maturation of oocytes was blocked in germinal vesicle (GV) stage by protein kinase A (PKA), MAPK14, MAPK3/1, and EGF receptor (EGFR) tyrosine kinase inhibitors (H89, SB203580, U0126, and AG1478 respectively) whereas phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene homolog (PI3K/AKT) inhibitor (LY294002) blocked maturation of oocytes in metaphase I (MI). Amphiregulin (AREG)-induced maturation of oocytes was efficiently blocked in GV by U0126, AG1478, and low concentrations of LY294002; H89, SB203580, and high concentrations of LY294002 allowed the oocytes to undergo breakdown of GV and blocked maturation in MI. Both FSH-and AREG-induced cumulus expansion was incompletely inhibited by H89 and completely inhibited by SB203580, U0126, AG1478, and LY294002. The inhibitors partially or completely inhibited expression of expansion-related genes (HAS2, PTGS2, and TNFAIP6) with two exceptions: H89 inhibited only TNFAIP6 expression and LY294002 increased expression of PTGS2. The results of this study are consistent with the idea that PKA and MAPK14 pathways are essential for FSH-induced transactivation of the EGFR, and synthesis of EGF-like peptides in cumulus cells and MAPK3/1 is involved in regulation of transcriptional and posttranscriptional events in cumulus cells required for meiotic resumption and cumulus expansion. PI3K/AKT signaling is important for regulation of cumulus expansion, AREG-induced meiotic resumption, and oocyte MI/MII transition. The present data also indicate the existence of an FSH-activated and PKA-independent pathway involved in regulation of HAS2 and PTGS2 expression in cumulus cells.

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Section: Signaling In Pig Cumulus-oocyte Complexesmentioning

confidence: 69%

Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption and cumulus cell expansion in the pig

Procházka¹,

Blaha²,

Němcová³

2012

Reproduction

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“…However, our current study opens up the possibility that granulosa and/or cumulus cells might regulate their responsiveness throughout folliculogenesis to oocyte factors such as GDF9 by modulating the basal or autocrine level of EGF receptor activity and resulting ERK1/2 phosphorylation. In support of the latter concept, Prochazka and collaborators (Prochazka et al, 2003) have shown that with progressive differentiation of pig cumulus cells through antral folliculogenesis, there is functional maturation of the EGFR. SFKs might play a key role in that context since it has been shown to act both upstream 3173 GDF9 requires ERK1/2 in granulosa cells and downstream of EGFR and to participate in its signal transduction (Bobe et al, 2003;Schauwienold et al, 2008).…”

Section: Journal Of Cell Science 123 (18)mentioning

confidence: 89%

Growth differentiation factor 9 signaling requires ERK1/2 activity in mouse granulosa and cumulus cells

Sasseville

Ritter

Nguyen

et al. 2010

Journal of Cell Science

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SummaryOvarian folliculogenesis is driven by the combined action of endocrine cues and paracrine factors. The oocyte secretes powerful mitogens, such as growth differentiation factor 9 (GDF9), that regulate granulosa cell proliferation, metabolism, steroidogenesis and differentiation. This study investigated the role of the epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase 1 and 2 (ERK1/2; also known as MAPK3/1) signaling pathway on GDF9 action on granulosa cells. Results show that mitogenic action of the oocyte is prevented by pharmacological inhibition of the EGFR-ERK1/2 pathway. Importantly, EGFR-ERK1/2 activity as well as rous sarcoma oncogene family kinases (SFK) are required for signaling through SMADs, mediating GDF9, activin A and TGF1 mitogenic action in granulosa cells. GDF9 could not activate ERK1/2 or affect EGF-stimulated ERK1/2 in granulosa cells. However, induction of the SMAD3-specific CAGA reporter by GDF9 in granulosa cells required active EGFR, SFKs and ERK1/2 as did GDF9-responsive gene expression. Finally, the EGFR-SFKs-ERK1/2 pathway was shown to be required for the maintenance of phosphorylation of the SMAD3 linker region. Together our results suggest that receptivity of granulosa cells to oocyte-secreted factors, including GDF9, is regulated by the level of activation of the EGFR and resulting ERK1/2 activity, through the requisite permissive phosphorylation of SMAD3 in the linker region. Our results indicate that oocyte-secreted TGF-like ligands and EGFR-ERK1/2 signaling are cooperatively required for the unique granulosa cell response to the signal from oocytes mediating granulosa cell survival and proliferation and hence the promotion of follicle growth and ovulation.

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“…We have shown in previous papers that the EGFR signaling plays an important role in the regulation of meiosis in the pig (Prochazka et al 2000(Prochazka et al , 2003. The aim of this work was to answer the question of whether EGF-like peptides can substitute for gonadotropins in stimulation of cumulus expansion, oocyte maturation, and acquisition of developmental competence in vitro or whether additional gonadotropin-induced signaling, besides the induction of the EGF-like peptides, is essential for occurrence of these events in pig COCs.…”

Section: Introductionmentioning

confidence: 99%

Effect of epidermal growth factor-like peptides on pig cumulus cell expansion, oocyte maturation, and acquisition of developmental competence in vitro: comparison with gonadotropins

Procházka

Petlach²,

Nagyová³

et al. 2011

Reproduction

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The aim of this work was to assess the FSH-stimulated expression of epidermal growth factor (EGF)-like peptides in cultured cumulusoocyte complexes (COCs) and to find out the effect of the peptides on cumulus expansion, oocyte maturation, and acquisition of developmental competence in vitro. FSH promptly stimulated expression of amphiregulin (AREG) and epiregulin (EREG), but not betacellulin (BTC) in the cultured COCs. Expression of AREG and EREG reached maximum at 2 or 4 h after FSH addition respectively. FSH also significantly stimulated expression of expansion-related genes (PTGS2, TNFAIP6, and HAS2) in the COCs at 4 and 8 h of culture, with a significant decrease at 20 h of culture. Both AREG and EREG also increased expression of the expansion-related genes; however, the relative abundance of mRNA for each gene was much lower than in the FSH-stimulated COCs. In contrast to FSH, AREG and EREG neither stimulated expression of CYP11A1 in the COCs nor an increase in progesterone production by cumulus cells. AREG and EREG stimulated maturation of oocytes and expansion of cumulus cells, although the percentage of oocytes that had reached metaphase II was significantly lower when compared to FSH-induced maturation. Nevertheless, significantly more oocytes stimulated with AREG and/or EREG developed to blastocyst stage after parthenogenetic activation when compared to oocytes stimulated with FSH alone or combinations of FSH/LH or pregnant mares serum gonadotrophin/human chorionic gonadotrophin. We conclude that EGF-like peptides do not mimic all effects of FSH on the cultured COCs; nevertheless, they yield oocytes with superior developmental competence.

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Epidermal Growth Factor-Receptor Tyrosine Kinase Activity Regulates Expansion of Porcine Oocyte-Cumulus Cell Complexes In Vitro1

Cited by 80 publications

References 53 publications

Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption and cumulus cell expansion in the pig

Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption and cumulus cell expansion in the pig

Growth differentiation factor 9 signaling requires ERK1/2 activity in mouse granulosa and cumulus cells

Effect of epidermal growth factor-like peptides on pig cumulus cell expansion, oocyte maturation, and acquisition of developmental competence in vitro: comparison with gonadotropins

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