A serine/threonine-specific protein kinase B (PKB), also known as Akt, is a key factor in the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway that regulates cell survival, metabolism and proliferation. Akt phosphorylates many downstream specific substrates, which subsequently control the nuclear envelope breakdown (NEBD), centrosome maturation, spindle assembly, chromosome segregation, and cytokinesis. In vertebrates, Akt is also an important player during oogenesis and preimplantation development. In the signaling pathways regulating mRNA translation, Akt is involved in the control of mammalian target of rapamycin complex 1 (mTORC1) and thereby regulates the activity of a translational repressor, the eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). In this review, we summarize the functions of Akt in mitosis, meiosis and early embryonic development. Additionally, the role of Akt in the regulation of mRNA translation is addressed with respect to the significance of this process during early development.

• Keywords
• Akt kinase, early embryo, mRNA translation, mTORC1, meiosis, mitosis, oocyte, spindle,
• MeSH
• Phosphatidylinositol 3-Kinase metabolism   MeSH
• Embryonic Development MeSH
• Phosphatidylinositol 3-Kinases * metabolism   MeSH
• Phosphoproteins metabolism   MeSH
• Phosphorylation genetics   MeSH
• Oocytes metabolism   MeSH
• Oogenesis MeSH
• Protein Serine-Threonine Kinases metabolism   MeSH
• Proto-Oncogene Proteins c-akt * metabolism   MeSH
• Mammals metabolism   MeSH
• Signal Transduction MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Phosphatidylinositol 3-Kinase MeSH
• Phosphatidylinositol 3-Kinases * MeSH
• Phosphoproteins MeSH
• Protein Serine-Threonine Kinases MeSH
• Proto-Oncogene Proteins c-akt * MeSH

The extracellular matrix (ECM) is an essential structure with biological activities. It has been shown that the ECM influences gene expression via cytoskeletal components and the gene expression is dependent upon cell interactions with molecules and hormones. The development of ovarian follicles is a hormone dependent process. The surge in the luteinizing hormone triggers ovulatory changes in oocyte microenvironment. In this review, we discuss how proteolytic cleavage affects formation of cumulus ECM following hormonal stimulation; in particular, how the specific proteasome inhibitor MG132 affects gonadotropin-induced cytoskeletal structure, the organization of cumulus ECM, steroidogenesis, and nuclear maturation. We found that after the inhibition of proteolytic cleavage, gonadotropin-stimulated oocyte-cumulus complexes (OCCs) were without any signs of cumulus expansion; they remained compact with preserved cytoskeletal F-actin-rich transzonal projections through the oocyte investments. Concomitantly, a significant decrease was detected in progesterone secretion and in the expression of gonadotropin-stimulated cumulus expansion-related transcripts, such as HAS2 and TNFAIP6. In agreement, the covalent binding between hyaluronan and the heavy chains of serum-derived the inter-alpha-trypsin inhibitor, essential for the organization of cumulus ECM, was missing.

• Keywords
• extracellular matrix, hyaluronan, oocyte–cumulus complex, proteasome,
• MeSH
• Cellular Microenvironment physiology   MeSH
• Extracellular Matrix physiology   MeSH
• Humans MeSH
• Oocytes physiology   MeSH
• Ovarian Follicle physiology   MeSH
• Proteolysis MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The developmental potential of porcine oocytes cultured in vitro was remarkably enhanced in a medium containing FGF2, LIF and IGF1 (FLI) when compared to a medium supplemented with gonadotropins and EGF (control). We analyzed the molecular background of the enhanced oocyte quality by comparing the time course of MAPK3/1 and AKT activation, and the expression of genes controlled by these kinases in cumulus-oocyte complexes (COCs) cultured in FLI and the control medium. The pattern of MAPK3/1 activation in COCs was very similar in both media, except for a robust increase in MAPK3/1 phosphorylation during the first hour of culture in the FLI medium. The COCs cultured in the FLI medium exhibited significantly higher activity of AKT than in the control medium from the beginning up to 16 h of culture; afterwards a deregulation of AKT activity occurred in the FLI medium, which was not observed in the control medium. The expression of cumulus cell genes controlled by both kinases was also modulated in the FLI medium, and in particular the genes related to cumulus-expansion, signaling, apoptosis, antioxidants, cell-to-cell communication, proliferation, and translation were significantly overexpressed. Collectively, these data indicate that both MAPK3/1 and AKT are implicated in the enhanced quality of oocytes cultured in FLI medium.

• Keywords
• AKT kinase, FGF2, IGF1, LIF, MAP kinase 3/1, gene expression, oocyte competence, oocyte maturation,
• MeSH
• In Vitro Oocyte Maturation Techniques methods   veterinary   MeSH
• Culture Media chemistry   pharmacology   MeSH
• Cells, Cultured MeSH
• Meiosis drug effects   physiology   MeSH
• Mitogen-Activated Protein Kinase 1 physiology   MeSH
• Mitogen-Activated Protein Kinase 3 physiology   MeSH
• Oocytes cytology   drug effects   physiology   MeSH
• Oogenesis drug effects   physiology   MeSH
• Swine MeSH
• Proto-Oncogene Proteins c-akt physiology   MeSH
• Signal Transduction drug effects   physiology   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Culture Media MeSH
• Mitogen-Activated Protein Kinase 1 MeSH
• Mitogen-Activated Protein Kinase 3 MeSH
• Proto-Oncogene Proteins c-akt MeSH

The maturation of mammalian oocytes in vitro can be stimulated by gonadotropins (follicle-stimulating hormone, FSH) or their intrafollicular mediator, epidermal growth factor (EGF)-like peptide-amphiregulin (AREG). We have shown previously that in pig cumulus-oocyte complexes (COCs), FSH induces expression and the synthesis of AREG that binds to EGF receptor (EGFR) and activates the mitogen-activated protein kinase 3/1 (MAPK3/1) signaling pathway. However, in this study we found that FSH also caused a rapid activation of MAPK3/1 in the cumulus cells, which cannot be explained by the de novo synthesis of AREG. The rapid MAPK3/1 activation required EGFR tyrosine kinase (TK) activity, was sensitive to SRC proto-oncogene non-receptor tyrosine kinase (SRC)-family and protein kinase C (PKC) inhibitors, and was resistant to inhibitors of protein kinase A (PKA) and metalloproteinases. AREG also induced the rapid activation of MAPK3/1 in cumulus cells, but this activation was only dependent on the EGFR TK activity. We conclude that in cumulus cells, FSH induces a rapid activation of MAPK3/1 by the ligand-independent transactivation of EGFR, requiring SRC and PKC activities. This rapid activation of MAPK3/1 precedes the second mechanism participating in the generation and maintenance of active MAPK3/1-the ligand-dependent activation of EGFR depending on the synthesis of EGF-like peptides.

• Keywords
• FSH, amphiregulin, cumulus cells, epidermal growth factor receptor, mitogen-activated protein kinase 3/1, signal transduction,
• MeSH
• Transcriptional Activation MeSH
• Amphiregulin metabolism   MeSH
• ErbB Receptors metabolism   MeSH
• Extracellular Signal-Regulated MAP Kinases genetics   MeSH
• Follicle Stimulating Hormone pharmacology   MeSH
• In Vitro Oocyte Maturation Techniques MeSH
• Cells, Cultured MeSH
• Cumulus Cells cytology   drug effects   metabolism   MeSH
• Mitogen-Activated Protein Kinase 1 genetics   MeSH
• Mitogen-Activated Protein Kinase 3 genetics   MeSH
• Oocytes cytology   drug effects   metabolism   MeSH
• Swine MeSH
• Signal Transduction drug effects   MeSH
• src-Family Kinases metabolism   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amphiregulin MeSH
• ErbB Receptors MeSH
• Extracellular Signal-Regulated MAP Kinases MeSH
• Follicle Stimulating Hormone MeSH
• Mitogen-Activated Protein Kinase 1 MeSH
• Mitogen-Activated Protein Kinase 3 MeSH
• src-Family Kinases MeSH

In vivo, resumption of oocyte meiosis occurs in large ovarian follicles after the preovulatory surge of luteinizing hormone (LH). The LH surge leads to the activation of a broad signaling network in mural granulosa cells equipped with LH receptors. The signals generated in the mural granulosa cells are further augmented by locally produced peptides or steroids and transferred to the cumulus cell compartment and the oocyte itself. Over the last decade, essential progress has been made in the identification of molecular events associated with the final maturation and ovulation of mammalian oocytes. All new evidence argues for a multiple roles of mitogen-activated protein kinase 3/1 (MAPK3/1) in the gonadotropin-induced ovulation processes. However, the knowledge of gonadotropin-induced signaling pathways leading to MAPK3/1 activation in follicular cells seems limited. To date, only the LH-induced transactivation of the epidermal growth factor receptor/MAPK3/1 pathway has been described in granulosa/cumulus cells even though other mechanisms of MAPK3/1 activation have been detected in other types of cells. In this review, we aimed to summarize recent advances in the elucidation of gonadotropin-induced mechanisms leading to the activation of MAPK3/1 in preovulatory follicles and cultured cumulus-oocyte complexes and to point out a specific role of this kinase in the processes accompanying final maturation of the mammalian oocyte.

• MeSH
• Granulosa Cells metabolism   MeSH
• MAP Kinase Signaling System genetics   MeSH
• Meiosis physiology   MeSH
• Mitogen-Activated Protein Kinase 1 metabolism   MeSH
• Mitogen-Activated Protein Kinase 3 metabolism   MeSH
• Mutation MeSH
• Mice MeSH
• Oocytes physiology   MeSH
• Steroids biosynthesis   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Mitogen-Activated Protein Kinase 1 MeSH
• Mitogen-Activated Protein Kinase 3 MeSH
• Steroids MeSH

BACKGROUND: The gonadotropin-induced resumption of oocyte meiosis in preovulatory follicles is preceded by expression of epidermal growth factor (EGF)-like peptides, amphiregulin (AREG) and epiregulin (EREG), in mural granulosa and cumulus cells. Both the gonadotropins and the EGF-like peptides possess the capacity to stimulate resumption of oocyte meiosis in vitro via activation of a broad signaling network in cumulus cells. To better understand the rapid genomic actions of gonadotropins (FSH) and EGF-like peptides, we analyzed transcriptomes of cumulus cells at 3 h after their stimulation. METHODS: We hybridized aRNA from cumulus cells to a pig oligonucleotide microarray and compared the transcriptomes of FSH- and AREG/EREG-stimulated cumulus cells with untreated control cells and vice versa. The identified over- and underexpressed genes were subjected to functional genomic analysis according to their molecular and cellular functions. The expression pattern of 50 selected genes with a known or potential function in ovarian development was verified by real-time qRT-PCR. RESULTS: Both FSH and AREG/EREG increased the expression of genes associated with regulation of cell proliferation, cell migration, blood coagulation and extracellular matrix remodeling. FSH alone induced the expression of genes involved in inflammatory response and in the response to reactive oxygen species. Moreover, FSH stimulated the expression of genes closely related to some ovulatory events either exclusively or significantly more than AREG/EREG (AREG, ADAMTS1, HAS2, TNFAIP6, PLAUR, PLAT, and HSD17B7). In contrast to AREG/EREG, FSH also increased the expression of genes coding for key transcription factors (CEBPB, FOS, ID1/3, and NR5A2), which may contribute to the differing expression profiles of FSH- and AREG/EREG-treated cumulus cells. CONCLUSIONS: The impact of FSH on cumulus cell gene transcription was higher than the impact of EGF-like factors in terms of the number of cell functions affected as well as the number of over- and underexpressed genes. Both FSH and EGF-like factors overexpressed genes involved in the post-ovulatory switch in steroidogenesis and tissue remodelling. However, FSH was remarkably more efficient in the up-regulation of several specific genes essential for ovulation of matured oocytes and also genes that been reported to play an important role in maturation of cumulus-enclosed oocytes in vitro.

• MeSH
• Amphiregulin pharmacology   physiology   MeSH
• Epidermal Growth Factor pharmacology   physiology   MeSH
• Epiregulin pharmacology   physiology   MeSH
• Follicle Stimulating Hormone pharmacology   physiology   MeSH
• Cells, Cultured MeSH
• Cumulus Cells drug effects   metabolism   MeSH
• Oocytes drug effects   metabolism   MeSH
• Swine MeSH
• Gene Expression Regulation MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amphiregulin MeSH
• Epidermal Growth Factor MeSH
• Epiregulin MeSH
• Follicle Stimulating Hormone MeSH

Hydrogen sulfide (H2S) has been revealed to be a signal molecule with second messenger action in the somatic cells of many tissues, including the reproductive tract. The aim of this study was to address how exogenous H2S acts on the meiotic maturation of porcine oocytes, including key maturation factors such as MPF and MAPK, and cumulus expansion intensity of cumulus-oocyte complexes. We observed that the H2S donor, Na2S, accelerated oocyte in vitro maturation in a dose-dependent manner, following an increase of MPF activity around germinal vesicle breakdown. Concurrently, the H2S donor affected cumulus expansion, monitored by hyaluronic acid production. Our results suggest that the H2S donor influences oocyte maturation and thus also participates in the regulation of cumulus expansion. The exogenous H2S donor apparently affects key signal pathways of oocyte maturation and cumulus expansion, resulting in faster oocyte maturation with little need of cumulus expansion.

• MeSH
• Extracellular Signal-Regulated MAP Kinases metabolism   MeSH
• Maturation-Promoting Factor metabolism   MeSH
• Gasotransmitters pharmacology   MeSH
• Coculture Techniques MeSH
• Cells, Cultured MeSH
• Cumulus Cells cytology   metabolism   MeSH
• Meiosis drug effects   MeSH
• Oocytes cytology   metabolism   MeSH
• Swine MeSH
• Hydrogen Sulfide pharmacology   MeSH
• Sulfides pharmacology   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Extracellular Signal-Regulated MAP Kinases MeSH
• Maturation-Promoting Factor MeSH
• Gasotransmitters MeSH
• sodium sulfide MeSH Browser
• Hydrogen Sulfide MeSH
• Sulfides MeSH