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Dev Biol
2008 Apr 01;3161:124-34. doi: 10.1016/j.ydbio.2008.01.018.
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Generation of mouse oocytes defective in cAMP synthesis and degradation: endogenous cyclic AMP is essential for meiotic arrest.
Vaccari S, Horner K, Mehlmann LM, Conti M.
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Although it is established that cAMP accumulation plays a pivotal role in preventing meiotic resumption in mammalian oocytes, the mechanisms controlling cAMP levels in the female gamete have remained elusive. Both production of cAMP via GPCRs/Gs/adenylyl cyclases endogenous to the oocyte as well as diffusion from the somatic compartment through gap junctions have been implicated in maintaining cAMP at levels that preclude maturation. Here we have used a genetic approach to investigate the different biochemical pathways contributing to cAMP accumulation and maturation in mouse oocytes. Because cAMP hydrolysis is greatly decreased and cAMP accumulates above a threshold, oocytes deficient in PDE3A do not resume meiosis in vitro or in vivo, resulting in complete female infertility. In vitro, inactivation of Gs or downregulation of the GPCR GPR3 causes meiotic resumption in the Pde3a null oocytes. Crossing of Pde3a(-/-) mice with Gpr3(-/-) mice causes partial recovery of female fertility. Unlike the complete meiotic block of the Pde3a null mice, oocyte maturation is restored in the double knockout, although it occurs prematurely as described for the Gpr3(-/-) mouse. The increase in cAMP that follows PDE3A ablation is not detected in double mutant oocytes, confirming that GPR3 functions upstream of PDE3A in the regulation of oocyte cAMP. Metabolic coupling between oocytes and granulosa cells was not affected in follicles from the single or double mutant mice, suggesting that diffusion of cAMP is not prevented. Finally, simultaneous ablation of GPR12, an additional receptor expressed in the oocyte, does not modify the Gpr3(-/-) phenotype. Taken together, these findings demonstrate that Gpr3 is epistatic to Pde3a and that fertility as well as meiotic arrest in the PDE3A-deficient oocyte is dependent on the activity of GPR3. These findings also suggest that cAMP diffusion through gap junctions or the activity of additional receptors is not sufficient by itself to maintain the meiotic arrest in the mouse oocyte.
Aberdam,
Maintenance of meiotic arrest in isolated rat oocytes by the invasive adenylate cyclase of Bordetella pertussis.
1987, Pubmed
Aberdam,
Maintenance of meiotic arrest in isolated rat oocytes by the invasive adenylate cyclase of Bordetella pertussis.
1987,
Pubmed Ackert,
Intercellular communication via connexin43 gap junctions is required for ovarian folliculogenesis in the mouse.
2001,
Pubmed Anderson,
Gap junctions between the oocyte and companion follicle cells in the mammalian ovary.
1976,
Pubmed Bornslaeger,
Regulation of mouse oocyte maturation: effect of elevating cumulus cell cAMP on oocyte cAMP levels.
1985,
Pubmed Chesnel,
Acquisition of meiotic competence by denuded mouse oocytes: participation of somatic-cell product(s) and cAMP.
1994,
Pubmed Conti,
Role of cyclic nucleotide signaling in oocyte maturation.
2002,
Pubmed
,
Xenbase de Groot,
Conduction slowing by the gap junctional uncoupler carbenoxolone.
2003,
Pubmed Dekel,
Spontaneous maturation in vitro of cumulus-enclosed rat oocytes is inhibited by forskolin.
1984,
Pubmed Dekel,
Induction of maturation of rat oocytes by interruption of communication in the cumulus-oocyte complex.
1991,
Pubmed Dekel,
Modulation of cell-to-cell communication in the cumulus-oocyte complex and the regulation of oocyte maturation by LH.
1981,
Pubmed Dekel,
Induction of maturation in rat follicle-enclosed oocyte by forskolin.
1983,
Pubmed Dekel,
Rat oocyte maturation in vitro: relief of cyclic AMP inhibition by gonadotropins.
1978,
Pubmed Duckworth,
G2 arrest in Xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A.
2002,
Pubmed
,
Xenbase Edwards,
Maturation in vitro of mouse, sheep, cow, pig, rhesus monkey and human ovarian oocytes.
1965,
Pubmed Eppig,
Inhibition of oocyte maturation in the mouse: participation of cAMP, steroid hormones, and a putative maturation-inhibitory factor.
1983,
Pubmed Eppig,
Production of cumulus expansion enabling factor by mouse oocytes grown in vitro: preliminary characterization of the factor.
1993,
Pubmed Eppig,
Chemical signals that regulate mammalian oocyte maturation.
1984,
Pubmed Eppig,
Isolation and culture of oocytes.
1993,
Pubmed Eppig,
The effect of hypoxanthine on mouse oocyte growth and development in vitro: maintenance of meiotic arrest and gonadotropin-induced oocyte maturation.
1987,
Pubmed Faucheux,
Gap junction communication between cells aggregated on a cellulose-coated polystyrene: influence of connexin 43 phosphorylation.
2004,
Pubmed Freudzon,
Regulation of meiotic prophase arrest in mouse oocytes by GPR3, a constitutive activator of the Gs G protein.
2005,
Pubmed Gallo,
Stimulation of Xenopus oocyte maturation by inhibition of the G-protein alpha S subunit, a component of the plasma membrane and yolk platelet membranes.
1995,
Pubmed
,
Xenbase Granot,
Phosphorylation and expression of connexin-43 ovarian gap junction protein are regulated by luteinizing hormone.
1994,
Pubmed Han,
Wee1B is an oocyte-specific kinase involved in the control of meiotic arrest in the mouse.
2005,
Pubmed
,
Xenbase Han,
Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation.
2006,
Pubmed
,
Xenbase Harper,
Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0 acetylation by acetic anhydride in aqueous solution.
1975,
Pubmed Hillensjö,
Inhibitory effect of human follicular fluid upon the maturation of porcine oocytes in culture.
1978,
Pubmed Hillensjö,
Role of cyclic AMP in oocyte maturation and glycolysis in the pre-ovulatory rat follicle.
1978,
Pubmed Hinckley,
The G-protein-coupled receptors GPR3 and GPR12 are involved in cAMP signaling and maintenance of meiotic arrest in rodent oocytes.
2005,
Pubmed
,
Xenbase Horner,
Rodent oocytes express an active adenylyl cyclase required for meiotic arrest.
2003,
Pubmed Kalinowski,
Maintenance of meiotic prophase arrest in vertebrate oocytes by a Gs protein-mediated pathway.
2004,
Pubmed
,
Xenbase Lampe,
The effects of connexin phosphorylation on gap junctional communication.
2004,
Pubmed Lampe,
Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.
2000,
Pubmed Lampe,
Regulation of gap junctions by phosphorylation of connexins.
2000,
Pubmed Larsen,
A dramatic loss of cumulus cell gap junctions is correlated with germinal vesicle breakdown in rat oocytes.
1986,
Pubmed Larsen,
Differential modulation of rat follicle cell gap junction populations at ovulation.
1987,
Pubmed Ledent,
Premature ovarian aging in mice deficient for Gpr3.
2005,
Pubmed Masciarelli,
Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility.
2004,
Pubmed Mehlmann,
The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes.
2004,
Pubmed Mehlmann,
Regulation of intracellular calcium in the mouse egg: calcium release in response to sperm or inositol trisphosphate is enhanced after meiotic maturation.
1994,
Pubmed Mehlmann,
Meiotic arrest in the mouse follicle maintained by a Gs protein in the oocyte.
2002,
Pubmed Mehlmann,
Oocyte-specific expression of Gpr3 is required for the maintenance of meiotic arrest in mouse oocytes.
2005,
Pubmed Newhall,
Dynamic anchoring of PKA is essential during oocyte maturation.
2006,
Pubmed O'Brien,
A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence.
2003,
Pubmed Pincus,
Can Mammalian Eggs Undergo Normal Development in Vitro?
1934,
Pubmed Quinn,
Preservation of hamster oocytes to assay the fertilizing capacity of human spermatozoa.
1982,
Pubmed Racowsky,
Down-regulation of membrana granulosa cell gap junctions is correlated with irreversible commitment to resume meiosis in golden Syrian hamster oocytes.
1989,
Pubmed Schultz,
Regulation of oocyte maturation in the mouse: possible roles of intercellular communication, cAMP, and testosterone.
1983,
Pubmed Sela-Abramovich,
Disruption of gap junctional communication within the ovarian follicle induces oocyte maturation.
2006,
Pubmed Simonds,
Gi2 mediates alpha 2-adrenergic inhibition of adenylyl cyclase in platelet membranes: in situ identification with G alpha C-terminal antibodies.
1989,
Pubmed Teilmann,
Differential expression and localisation of connexin-37 and connexin-43 in follicles of different stages in the 4-week-old mouse ovary.
2005,
Pubmed TenBroek,
Ser364 of connexin43 and the upregulation of gap junction assembly by cAMP.
2001,
Pubmed Thomas,
Effect of specific phosphodiesterase isoenzyme inhibitors during in vitro maturation of bovine oocytes on meiotic and developmental capacity.
2004,
Pubmed Törnell,
Resumption of rat oocyte meiosis is paralleled by a decrease in guanosine 3',5'-cyclic monophosphate (cGMP) and is inhibited by microinjection of cGMP.
1990,
Pubmed Tsafriri,
Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors.
1996,
Pubmed Tsafriri,
In-vitro induction of meiotic division in follicle-enclosed rat oocytes by LH, cyclic AMP and prostaglandin E 2 .
1972,
Pubmed Urschel,
Protein kinase A-mediated phosphorylation of connexin36 in mouse retina results in decreased gap junctional communication between AII amacrine cells.
2006,
Pubmed Veitch,
Selective assembly of connexin37 into heterocellular gap junctions at the oocyte/granulosa cell interface.
2004,
Pubmed Vivarelli,
Meiotic resumption and intracellular cAMP levels in mouse oocytes treated with compounds which act on cAMP metabolism.
1983,
Pubmed Wang,
A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo.
2004,
Pubmed Wassarman,
RNA synthesis in fully-grown mouse oocytes.
1976,
Pubmed Webb,
Follicle-stimulating hormone induces a gap junction-dependent dynamic change in [cAMP] and protein kinase a in mammalian oocytes.
2002,
Pubmed Wert,
Preendocytotic alterations in cumulus cell gap junctions precede meiotic resumption in the rat cumulus-oocyte complex.
1990,
Pubmed Wiersma,
Phosphodiesterase 3 inhibitors suppress oocyte maturation and consequent pregnancy without affecting ovulation and cyclicity in rodents.
1998,
Pubmed Yogo,
PKA implicated in the phosphorylation of Cx43 induced by stimulation with FSH in rat granulosa cells.
2006,
Pubmed Yoshimura,
Stimulatory role of cyclic adenosine monophosphate as a mediator of meiotic resumption in rabbit oocytes.
1992,
Pubmed Yoshimura,
Induction of meiotic maturation of follicle-enclosed oocytes of rabbits by a transient increase followed by an abrupt decrease in cyclic AMP concentration.
1992,
Pubmed
