Structure-function analysis of the plasma protein fetuin-B

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The plasma protein fetuin-B is essential for the fertilization of oocytes. Fetuin-B is a potent inhibitor of the proteinase ovastacin preventing premature activity of ovastacin during oocyte maturation. Thus fetuin-B maintains the fertility of the oocyte. In the absence of the inhibitor ovastacin cleaves zona pellucida protein ZP2 thus mediating major structural changes of the oocyte extracellular matrix. This process is generally known as zona pellucida “hardening”. Following zona pellucida hardening sperm is unable to bind, penetrated and fertilize the oocyte. Fetuin-B deficient female mice are completely infertile, because their oocytes have a prematurely hardened zona pellucida. In this research proposal we plan to gain mechanistic knowledge about the specific interaction between fetuin-B (inhibitor) and ovastacin (proteinase). We ask if the interaction between fetuin-B and ovastacin is only important before fertilization or also during the early embryo development and hatching. We will determine structural features, which are essential for the inhibition of ovastacin. The knowledge will aid the development of innovative non-hormonal contraceptive therapies, and will also help do develop therapeutic strategies for women with idiopathic infertility. About 15% of couples have an unfulfilled desire for a child. To optimize the assisted reproductive therapies, novel parameters for oocyte quality control are highly desirable. We will study nanoindentation of oocyte as a quick, unbiased and non-destructive method for oocyte quality control.