Caffeine alleviates the deterioration of Ca 2+ release mechanisms and fragmentation of in vitro-aged mouse eggs

Nan Zhang, Takuya Wakai, Rafael A. Fissore

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


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 3R1, the major Ca 2+ release channel at fertilization, was undermined in in vitro-aged mouse eggs. We found that in aged eggs, IP 3R1 displayed reduced function as many of the changes acquired during maturation that enhance IP 3R1 Ca 2+ conductivity, such as phosphorylation, receptor reorganization and increased Ca 2+ store content ([Ca 2+] ER), were lost with increasing postovulatory time. IP 3R1 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 3R 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 3R1 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.

Original languageEnglish
Pages (from-to)684-701
Number of pages18
JournalMolecular Reproduction and Development
Issue number9
Publication statusPublished - Sept 2011
Externally publishedYes


  • Anti-aging treatment
  • Caffeine
  • Calcium homeostasis
  • Fertilization
  • IP R1
  • Oocyte quality
  • Postovulatory egg aging

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology


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