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Oocyte Activation and Phospholipase C Zeta (PLCζ): Male Infertility and Implications for Therapeutic Intervention

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Phospholipases in Health and Disease

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 10))

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Abstract

Infertility is a condition that now affects an estimated one in seven couples. In approximately 40 % of cases, the primary cause of infertility rests with male-derived factors associated with a variety of anatomical, physiological, and molecular deficiencies. In a proportion of such cases, the functional ability of sperm to successfully fertilise and activate the oocyte is compromised. While assisted reproductive technology can successfully circumvent some of these issues via the application of artificial oocyte-activating agents, there is significant ongoing debate as to whether these chemical agents should be replaced with an endogenous alternative. Phospholipase C zeta (PLCζ) is the sperm-specific protein responsible for activating the quiescent oocyte following gamete fusion. Identified in a number of mammalian and non-mammalian organisms, PLCζ plays a fundamental role in the process of oocyte activation by inducing the controlled release of calcium in the ooplasm via an inositol triphosphate (IP3)-mediated signalling cascade. A growing body of evidence shows clear association between abnormalities in PLCζ structure, expression, localisation, and function to characterised states of human male infertility. Consequently there is significant global interest in PLCζ as both an endogenous therapeutic target to rescue infertile states associated with PLCζ-linked oocyte activation deficiency, and a diagnostic marker for oocyte activation ability. Here, we discuss the present status of PLCζ research and contemplate future applications of this fundamental sperm PLC in the clinic.

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    Authors and Affiliations

    1. Nuffield Department of Obstetrics and Gynaecology, Level 3, Women’s Centre, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK

      Junaid Kashir, Celine Jones & Kevin Coward

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    1. Junaid Kashir
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    2. Celine Jones
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    3. Kevin Coward
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    Correspondence to Kevin Coward .

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    1. I.H. Asper Clinical Research Institute St. Boniface Hospital Research, Winnipeg, Manitoba, Canada

      Paramjit S. Tappia

    2. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

      Naranjan S. Dhalla

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    Kashir, J., Jones, C., Coward, K. (2014). Oocyte Activation and Phospholipase C Zeta (PLCζ): Male Infertility and Implications for Therapeutic Intervention. In: Tappia, P., Dhalla, N. (eds) Phospholipases in Health and Disease. Advances in Biochemistry in Health and Disease, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0464-8_16

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