1. Introduction to the mammalian egg activation

• Ca2+ Rise in the mammalian Egg Activation:
  • In mammals, transient rise in cytoplasmic Ca2+ is essential for egg activation.
  • Sperm induces Ca2+ waves lasting hours, leading to egg activation.
  • Key events: resumption of meiosis, cortical granule exocytosis, and release of maternal mRNAs.
  • Similar to sea urchins, intracellular Ca2+ release triggered by IP3 production.

2. Sperm-Derived PLCζ: A Surprising Discovery

• Intracytoplasmic Sperm Injection (ICSI):
  • ICSI bypasses egg cell membrane interaction by directly injecting sperm into oocyte cytoplasm.
  • Contrary to assumptions, ICSI successfully activates human eggs and forms pronuclei.
  • Mouse sperm injected into mouse eggs also induces Ca2+ oscillations and development.
• Sperm-Derived PLCζ:
  • Stored in sperm head, delivered to egg during gamete fusion.
  • PLCζ mRNA expression in egg produces Ca2+ oscillations.
  • Removing PLCζ from mouse sperm abolishes calcium-inducing activity.
  • Human sperm lacking functional PLCζ fail in ICSI.

3. Ca2+ Oscillations in Mammalian Eggs

• Multiple Waves of Calcium Ions:
  • Unlike sea urchins, mammalian eggs experience numerous Ca2+ oscillations.
  • Oscillation extent (amplitude, duration, number) regulates egg activation timing.
  • Cortical granule exocytosis occurs before meiosis resumes and maternal mRNA translation.
• Ca2+ Binding Proteins and Functions:
  • IP3-released Ca2+ binds to proteins:
    • Calmodulin-activated protein kinase (eliminates mRNA translation inhibitors).
    • MAP kinase (resumes meiosis).
    • Synaptotagmin (initiates cortical granule fusion).
  • Unused Ca2+ pumped back into endoplasmic reticulum.
  • Extracellular Ca2+ recruitment essential for completing meiosis.
  • Blocked Ca2+ influx results in nonviable (triploid) egg pronuclei.