Where Life Begins: Sperm PLCζ in Mammalian Egg Activation and Implications in Male Infertility

  • Michail Nomikos
  • Maria Theodoridou
  • F. Anthony Lai
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 10)


Egg activation is the earliest step of embryonic development following mammalian fertilization and is triggered by a characteristic series of cytoplasmic calcium (Ca2+) transients, known as Ca2+ oscillations. It has been proposed that following sperm–egg fusion in mammals, it is the fertilizing sperm that causes these Ca2+ oscillations by introducing a sperm-specific protein factor into the egg cytoplasm. Mounting scientific and clinical evidence supports the notion that this protein is a sperm-specific phospholipase C (PLC), PLC-zeta (PLCζ). PLCζ has been singularly shown to stimulate cytoplasmic Ca2+ oscillations matching those at fertilization that trigger the early events of embryo development in many mammalian species. Sperm-delivered PLCζ is responsible for catalyzing phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis within the fertilized egg stimulating the inositol 1,4,5-trisphosphate (IP3) signaling pathway, leading to Ca2+ oscillations. PLC zeta (PLCζ) is the smallest with the most elementary domain organization among all mammalian PLC isoforms, exhibiting a typical PLC domain structure. Importantly, the role of PLCζ in mammalian fertilization is highlighted by a number of recent clinical reports that have linked defects in human PLCζ with cases of egg activation deficiency resulting in male infertility. Herein, we describe the current paradigm of PLCζ in this fundamental biological process, summarizing recent important advances in our knowledge of the biochemical and physiological properties of this enzyme that is so crucial to successful fertilization and embryogenesis. We also describe how PLCζ is linked to cases of egg activation deficiencies and postulate the therapeutic and diagnostic roles this enzyme presents within a clinical setting.


Sperm Phospholipase C PLC zeta Inositol 1,4,5 trisphosphate Calcium oscillations Egg activation Development Embryogenesis Fertilization Infertility 



We are grateful for grant support from the Wellcome Trust and helpful discussion with Professor Karl Swann.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Cell Signalling Laboratory, Institute of Molecular and Experimental MedicineWHRI, Cardiff University School of MedicineCardiffUK

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