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.

• Klíčová slova
• Akt kinase, early embryo, mRNA translation, mTORC1, meiosis, mitosis, oocyte, spindle,
• MeSH
• 1-fosfatidylinositol-3-kinasa metabolismus   MeSH
• embryonální vývoj MeSH
• fosfatidylinositol-3-kinasy * metabolismus   MeSH
• fosfoproteiny metabolismus   MeSH
• fosforylace genetika   MeSH
• oocyty metabolismus   MeSH
• oogeneze MeSH
• protein-serin-threoninkinasy metabolismus   MeSH
• protoonkogenní proteiny c-akt * metabolismus   MeSH
• savci metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• 1-fosfatidylinositol-3-kinasa MeSH
• fosfatidylinositol-3-kinasy * MeSH
• fosfoproteiny MeSH
• protein-serin-threoninkinasy MeSH
• protoonkogenní proteiny c-akt * MeSH

Cells are equipped with a diverse network of signaling and regulatory proteins that function as cell cycle regulators and checkpoint proteins to ensure the proper progression of cell division. A key regulator of cell division is polo-like kinase 1 (PLK1), a member of the serine/threonine kinase family that plays an important role in regulating the mitotic and meiotic cell cycle. The phosphorylation of specific substrates mediated by PLK1 controls nuclear envelope breakdown (NEBD), centrosome maturation, proper spindle assembly, chromosome segregation, and cytokinesis. In mammalian oogenesis, PLK1 is essential for resuming meiosis before ovulation and for establishing the meiotic spindle. Among other potential roles, PLK1 regulates the localized translation of spindle-enriched mRNAs by phosphorylating and thereby inhibiting the translational repressor 4E-BP1, a downstream target of the mTOR (mammalian target of rapamycin) pathway. In this review, we summarize the functions of PLK1 in mitosis, meiosis, and cytokinesis and focus on the role of PLK1 in regulating mRNA translation. However, knowledge of the role of PLK1 in the regulation of meiosis remains limited.

• Klíčová slova
• PLK1, mRNA translation, meiosis, mitosis, oocytes, polo-like kinase 1, spindle,
• MeSH
• lidé MeSH
• meióza MeSH
• mitóza MeSH
• polo-like kinasa 1 MeSH
• protein-serin-threoninkinasy * metabolismus   MeSH
• proteiny buněčného cyklu * metabolismus   MeSH
• protoonkogenní proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• protein-serin-threoninkinasy * MeSH
• proteiny buněčného cyklu * MeSH
• protoonkogenní proteiny MeSH

Germ cell quality is a key prerequisite for successful fertilization and early embryo development. The quality is determined by the fine regulation of transcriptomic and proteomic profiles, which are prone to alteration by assisted reproduction technology (ART)-introduced in vitro methods. Gaining evidence shows the ART can influence preset epigenetic modifications within cultured oocytes or early embryos and affect their developmental competency. The aim of this review is to describe ART-determined epigenetic changes related to the oogenesis, early embryogenesis, and further in utero development. We confront the latest epigenetic, related epitranscriptomic, and translational regulation findings with the processes of meiotic maturation, fertilization, and early embryogenesis that impact the developmental competency and embryo quality. Post-ART embryo transfer, in utero implantation, and development (placentation, fetal development) are influenced by environmental and lifestyle factors. The review is emphasizing their epigenetic and ART contribution to fetal development. An epigenetic parallel among mouse, porcine, and bovine animal models and human ART is drawn to illustrate possible future mechanisms of infertility management as well as increase the awareness of the underlying mechanisms governing oocyte and embryo developmental complexity under ART conditions.

• Klíčová slova
• embryo development, epigenetics, oocyte maturation, protein translation,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of CDK1 in the initiation and elongation steps of protein synthesis in the cell. During its activation, CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1 to optimize temporal synthesis of proteins to sustain the division-related processes: mitosis and cytokinesis.

• Klíčová slova
• 4E-BP1, CDK1, M-phase, mRNA, mTOR, translation,
• MeSH
• buněčný cyklus genetika   fyziologie   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• proteinkinasa CDC2 genetika   metabolismus   MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• TOR serin-threoninkinasy genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• messenger RNA MeSH
• proteinkinasa CDC2 MeSH
• proteiny buněčného cyklu MeSH
• TOR serin-threoninkinasy MeSH

In the mammalian ovary, the hyaluronan (HA)-rich cumulus extracellular matrix (ECM) organized during the gonadotropin-induced process of oocyte maturation is essential for ovulation of the oocyte-cumulus complex (OCC) and fertilization. Versican is an HA-binding proteoglycan that regulates cell function and ECM assembly. Versican cleavage and function remain to be determined in ovarian follicle. We investigated versican expression in porcine ovarian follicles by real-time (RT)-PCR and western blotting. The aims of the present work were to determine whether 1) versican was produced and cleaved by porcine OCCs during gonadotropin stimulation; 2) these processes were autonomous or required the participation of mural granulosa cells (MGCs); and 3) versican cleavage was involved in the formation or degradation of expanded cumulus ECM. We demonstrate two cleavage products of G1 domain of versican (V1) accumulated in the HA-rich cumulus ECM. One of them, a G1-DPEAAE N-terminal fragment (VG1) of ~70 kDa, was generated from V1 during organization of HA in in vivo and in vitro expanded porcine OCCs. Second, the V1-cleaved DPEAAE-positive form of ~65 kDa was the only species detected in MGCs. No versican cleavage products were detected in OCCs cultured without follicular fluid. In summary, porcine OCCs are autonomous in producing and cleaving V1; the cleaved fragment of ~70 kDa VG1 is specific for formation of the expanded cumulus HA-rich ECM.

• Klíčová slova
• extracellular matrix, hyaluronan, oocyte-cumulus complex, versican,
• MeSH
• buněčná diferenciace MeSH
• epitopy imunologie   MeSH
• kultivované buňky MeSH
• oocyty cytologie   imunologie   metabolismus   MeSH
• prasata MeSH
• versikany genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• epitopy MeSH
• versikany MeSH

Culture media used in assisted reproduction are commonly supplemented with gonadotropin hormones to support the nuclear and cytoplasmic maturation of in vitro matured oocytes. However, the effect of gonadotropins on protein synthesis in oocytes is yet to be fully understood. As published data have previously documented a positive in vitro effect of follicle-stimulating hormone (FSH) on cytoplasmic maturation, we exposed mouse denuded oocytes to FSH in order to evaluate the changes in global protein synthesis. We found that dose-dependent administration of FSH resulted in a decrease of methionine incorporation into de novo synthesized proteins in denuded mouse oocytes and oocytes cultured in cumulus-oocyte complexes. Similarly, FSH influenced methionine incorporation in additional mammalian species including human. Furthermore, we showed the expression of FSH-receptor protein in oocytes. We found that major translational regulators were not affected by FSH treatment; however, the amino acid uptake became impaired. We propose that the effect of FSH treatment on amino acid uptake is influenced by FSH receptor with the effect on oocyte metabolism and physiology.

• Klíčová slova
• FSH/FSH receptor, oocyte, oocyte maturation, translation,
• MeSH
• aminokyseliny metabolismus   MeSH
• folikuly stimulující hormon farmakologie   MeSH
• IVM techniky metody   MeSH
• kultivační média chemie   farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• myši MeSH
• oocyty účinky léků   metabolismus   MeSH
• prasata MeSH
• savci MeSH
• skot MeSH
• stadium rýhování vajíčka účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny MeSH
• folikuly stimulující hormon MeSH
• kultivační média MeSH

Although the involvement of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in the regulation of cytostatic factor (CSF) activity; as well as in microtubules organization during meiotic maturation of oocytes; has already been described in detail; rather less attention has been paid to the role of ERK1/2 in the regulation of mRNA translation. However; important data on the role of ERK1/2 in translation during oocyte meiosis have been documented. This review focuses on recent findings regarding the regulation of translation and the role of ERK1/2 in this process in the meiotic cycle of mammalian oocytes. The specific role of ERK1/2 in the regulation of mammalian target of rapamycin (mTOR); eukaryotic translation initiation factor 4E (eIF4E) and cytoplasmic polyadenylation element binding protein 1 (CPEB1) activity is addressed along with additional focus on the other key players involved in protein translation.

• Klíčová slova
• CPEB1, ERK1/2, MAP kinase, eIF4E, mTOR, oocyte, translation,
• MeSH
• cytoplazma genetika   metabolismus   MeSH
• eukaryotický iniciační faktor 4E metabolismus   MeSH
• faktory štěpení a polyadenylace mRNA metabolismus   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• lidé MeSH
• meióza * MeSH
• messenger RNA genetika   metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 1 metabolismus   MeSH
• mitogenem aktivovaná proteinkinasa 3 metabolismus   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• oocyty metabolismus   MeSH
• polyadenylace MeSH
• proteosyntéza * MeSH
• signální transdukce MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• vazba proteinů MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• eukaryotický iniciační faktor 4E MeSH
• faktory štěpení a polyadenylace mRNA MeSH
• messenger RNA MeSH
• mitogenem aktivovaná proteinkinasa 1 MeSH
• mitogenem aktivovaná proteinkinasa 3 MeSH
• mitogenem aktivované proteinkinasy MeSH
• TOR serin-threoninkinasy MeSH

OBJECTIVE: To determine whether inhibition of epidermal growth factor (EGF) receptor tyrosine kinase with lapatinib affects oocyte maturation, expression of the cumulus expansion-associated genes such as tumor necrosis factor alpha-induced protein 6 (TNFAIP6) and prostaglandin-endoperoxide synthase 2 (PTGS2), and synthesis of hyaluronan (HA) and progesterone (P) by porcine oocyte cumulus complexes (OCC). DESIGN: Our work focuses on lapatinib, an orally active small molecule that selectively inhibits the tyrosine kinase domain of both EGF receptor and human EGF receptor 2, and downstream signaling. SETTING: A reproductive biology laboratory. PATIENT(S): Not applicable. INTERVENTION(S): Porcine OCC were cultured in vitro in a medium with FSH/LH in the presence/absence of lapatinib. MAIN OUTCOME MEASURE(S): Methods performed: real-time reverse transcriptase-polymerase chain reaction (PCR), immunofluorescence, RIA. RESULT(S): In FSH/LH-stimulated and expanded cumulus oophorus extracellular matrix, HA was detected with biotinylated HA-binding proteins. However, weaker HA- and weaker cytoplasmic TNFAIP6 were detected were detected in lapatinib-pretreated OCC. The expression of the two cumulus expansion-associated gene transcripts was significantly decreased and synthesis of HA by cumulus cells was reduced. Lapatinib (10 μM) inhibited FSH/LH-induced oocyte meiotic maturation. Progesterone production increased after OCC stimulation with FSH/LH and was significantly decreased by lapatinib (10 μM). CONCLUSION(S): Lapatinib inhibits oocyte maturation and reduces expression of cumulus expansion-associated transcripts, and synthesis of HA and P in OCC cultured in vitro in FSH/LH-supplemented medium.

• MeSH
• buněčná diferenciace účinky léků   fyziologie   MeSH
• chinazoliny farmakologie   MeSH
• folikuly stimulující hormon farmakologie   MeSH
• inhibitory růstu farmakologie   MeSH
• kultivované buňky MeSH
• kumulární buňky cytologie   účinky léků   MeSH
• lapatinib MeSH
• meióza účinky léků   fyziologie   MeSH
• oocyty cytologie   účinky léků   MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chinazoliny MeSH
• folikuly stimulující hormon MeSH
• inhibitory růstu MeSH
• lapatinib MeSH

The aim of this study was to investigate the involvement of the serine/threonine protein kinase AKT (also called protein kinase B) in the control of meiosis of porcine denuded oocytes (DOs) matured in vitro. Western blot analysis revealed that the two principal AKT phosphorylation sites, Ser473 and Thr308, are phosphorylated at different stages of meiosis. In freshly isolated germinal vesicle (GV)-stage DOs, Ser473 was already phosphorylated. After the onset of oocyte maturation, the intensity of the Ser473 phosphorylation increased, however, which declined sharply when DOs underwent GV breakdown (GVBD) and remained at low levels in metaphase I- and II-stage (MI- and MII-stage). In contrast, phosphorylation of Thr308 was increased by the time of GVBD and reached maximum at MI-stage. A peak of AKT activity was noticed around GVBD and activity of AKT declined at MI-stage. To assess the role of AKT during meiosis, porcine DOs were cultured in 50 microM SH-6, a specific inhibitor of AKT. In SH-6-treated DOs, GVBD was not inhibited; on the contrary, a significant acceleration of meiosis resumption was observed. The dynamics of the Ser473 phosphorylation was not affected; however, phosphorylation of Thr308 was reduced, AKT activity was diminished at the time of GVBD, and meiotic progression was arrested in early MI-stage. Moreover, the activity of the cyclin-dependent kinase 1 (CDK1) and MAP kinase declined when SH-6-treated DOs underwent GVBD, indicating that AKT activity is involved in the regulation of CDK1 and MAP kinase. These results suggest that activity of AKT is not essential for induction of GVBD in porcine oocytes but plays a substantial role during progression of meiosis to MI/MII-stage.

• MeSH
• aktivace enzymů účinky léků   fyziologie   MeSH
• buněčné kultury MeSH
• dibutyryl cyklický AMP farmakologie   MeSH
• fosfatidylinositoly farmakologie   MeSH
• fosforylace účinky léků   MeSH
• inhibitory enzymů farmakologie   MeSH
• kultivované buňky MeSH
• meióza * fyziologie   MeSH
• onkogenní protein v-akt antagonisté a inhibitory   metabolismus   fyziologie   MeSH
• oocyty účinky léků   metabolismus   fyziologie   MeSH
• oogeneze účinky léků   fyziologie   MeSH
• prasata * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dibutyryl cyklický AMP MeSH
• fosfatidylinositoly MeSH
• inhibitory enzymů MeSH
• onkogenní protein v-akt MeSH
• SH-6 compound MeSH Prohlížeč

BACKGROUND INFORMATION: In fully grown mouse oocytes, a decrease in cAMP concentration precedes and is linked to CDK1 (cyclin-dependent kinase 1) activation. The molecular mechanism for this coupling, however, is not defined. PKB (protein kinase B, also called AKT) is implicated in CDK1 activation in lower species. During resumption of meiosis in starfish oocytes, MYT1, a negative regulator of CDK1, is phosphorylated by PKB in an inhibitory manner. It can imply that PKB is also involved in CDK1 activation in mammalian oocytes. RESULTS: We monitored activation of PKB and CDK1 during maturation of mouse oocytes. PKB phosphorylation and activation preceded GVBD (germinal vesicle breakdown) in oocytes maturing either in vitro or in vivo. Activation was transient and PKB activity was markedly reduced when virtually all of the oocytes had undergone GVBD. PKB activation was independent of CDK1 activity, because although butyrolactone I prevented CDK1 activation and GVBD, PKB was nevertheless transiently phosphorylated and activated. LY-294002, an inhibitor of phosphoinositide 3-kinase-PKB signalling, suppressed activation of PKB and CDK1 as well as resumption of meiosis. OA (okadaic acid)-sensitive phosphatases are involved in PKB-activity regulation, because OA induced PKB hyperphosphorylation. During resumption of meiosis, PKB phosphorylated on Ser(473) is associated with nuclear membrane and centrosome, whereas PKB phosphorylated on Thr(308) is localized on centrosome only. CONCLUSIONS: The results of the present paper indicate that PKB is involved in CDK1 activation and resumption of meiosis in mouse oocytes. The presence of phosphorylated PKB on centrosome at the time of GVBD suggests its important role for an initial CDK1 activation.

• MeSH
• aktivace enzymů MeSH
• centrozom metabolismus   MeSH
• chromony farmakologie   MeSH
• fosforylace MeSH
• gama-butyrolakton analogy a deriváty   farmakologie   MeSH
• jaderný obal metabolismus   MeSH
• kyselina okadaová farmakologie   MeSH
• meióza * MeSH
• morfoliny farmakologie   MeSH
• myši MeSH
• oocyty účinky léků   fyziologie   MeSH
• proteinkinasa CDC2 metabolismus   MeSH
• protoonkogenní proteiny c-akt antagonisté a inhibitory   fyziologie   MeSH
• serin metabolismus   MeSH
• techniky in vitro MeSH
• threonin metabolismus   MeSH
• transport proteinů MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one MeSH Prohlížeč
• butyrolactone I MeSH Prohlížeč
• chromony MeSH
• gama-butyrolakton MeSH
• kyselina okadaová MeSH
• morfoliny MeSH
• proteinkinasa CDC2 MeSH
• protoonkogenní proteiny c-akt MeSH
• serin MeSH
• threonin MeSH