title: Caffeine alleviates the deterioration of Ca(2+)  release mechanisms and fragmentation of in vitro-aged mouse eggs.
abstract: The developmental competence of mammalian eggs is compromised by postovulatory aging. We and others have found that in these eggs, the intracellular calcium ([Ca(2+)](i)) responses required for egg activation and initiation of development are altered. Nevertheless, the mechanism(s) underlying this defective Ca(2+) release is not well known. Here, we investigated if the function of IP(3)R1, the major Ca(2+) release channel at fertilization, was undermined in in vitro-aged mouse eggs. We found that in aged eggs, IP(3)R1 displayed reduced function as many of the changes acquired during maturation that enhance IP(3)R1 Ca(2+) conductivity, such as phosphorylation, receptor reorganization and increased Ca(2+) store content ([Ca(2+)](ER)), were lost with increasing postovulatory time. IP(3)R1 fragmentation, possibly associated with the activation of caspase-3, was also observed in these eggs. Many of these changes were prevented when the postovulatory aging of eggs was carried out in the presence of caffeine, which minimized the decline in IP(3)R(1) function and maintained [Ca(2+)](ER) content. Caffeine also maintained mitochondrial membrane potential, as measured by JC-1 fluorescence. We therefore conclude that [Ca(2+)](i) responses in aged eggs are undermined by reduced IP(3)R1 sensitivity, decreased [Ca(2+)](ER) , and compromised mitochondrial function, and that addition of caffeine ameliorates most of these aging-associated changes. Understanding the molecular basis of the protective effects of caffeine will be useful in elucidating, and possibly reversing, the signaling pathway(s) compromised by in vitro culture of eggs.
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Takuya
authors.initials: T
authors.lastname: Wakai
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Fissore
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D015151:Immunoblotting; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D010063:Ovum / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D002110:Caffeine; D002118:Calcium
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