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Content archived on 2024-06-18

Oocyte activation and human infertility: Identification and characterisation of a critical oocyte-borne receptor, and effects of laboratory procedures upon key proteins involved in oocyte activation

Objective

Mammalian sperm activate the oocyte at fertilisation by triggering a calcium-mediated pathway via PLCζ, a sperm-specific phospholipase. PLCζ deficiency is linked to human infertility, a condition that affects 1 in 7 couples. While intra-cytoplasmic sperm injection (ICSI) can rescue many types of male infertility, 1 – 5% of cases fail due to PLCζ-deficiency. While artificial activating agents are available, such chemicals do not initiate activation in an endogenous manner. Recombinant PLCζ thus represents a safer therapeutic option. However, we do not yet know how PLCζ interacts with oocyte-based factors in order to regulate functionality. Current opinion is that an unidentified protein resides within the ooplasm upon vesicles containing the substrate for PLCζ. Identifying this factor, and optimising the manner in which oocyte activation deficiency (OAD) can be diagnosed and treated, is a key clinical remit. Of equal concern is that the host laboratory showed that clinical treatments, such as cryopreservation, can cause detrimental effect upon PLCζ in human sperm. Consequently, this proposal has two objectives: 1) identify the oocyte-factor that interacts with PLCζ via the use of protein-protein interaction technologies, and 2) evaluate the impact of clinical procedures upon gamete proteins that play a critical role during activation. Research will involve human gametes sourced from the Oxford Fertility Unit, along with murine and bovine animal models. The proposal is targeted to (a) improve our understanding of PLCζ function, (b) establish whether the oocyte-interacting protein represents a novel diagnostic marker for OAD, and (c) develop our understanding of how clinical procedures can influence proteins in human gametes. While the proposal is primarily targeted to human reproductive medicine, results will be equally applicable to animals of economic interest, such as the controlled breeding programmes used for equine and bovine species.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2013-IEF
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Funding Scheme

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MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
EU contribution
€ 299 558,40
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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