Structure-function analysis of the plasma protein fetuin-B

血浆蛋白胎儿蛋白b对卵母细胞受精至关重要。Fetuin-B是一种有效的卵泡他星蛋白酶抑制剂，可防止卵泡他星在卵母细胞成熟过程中的过早活性。因此，胎儿蛋白b维持卵母细胞的生育能力。在缺乏抑制剂的情况下，卵泡他星可切割透明带蛋白ZP2，从而介导卵母细胞外基质的主要结构变化。这个过程通常被称为透明带“硬化”。随着透明带的硬化，精子无法结合、穿透并使卵母细胞受精。胎儿蛋白b缺乏的雌性小鼠完全不能生育，因为它们的卵母细胞有一个过早硬化的透明带。在这项研究计划中，我们计划获得关于胎儿素- b（抑制剂）和ovastacin（蛋白酶）之间特异性相互作用的机制知识。我们想知道胎儿素b和卵泡他星之间的相互作用是否只在受精前重要，还是在胚胎早期发育和孵化过程中也重要。我们将确定结构特征，这对抑制奥伐他星至关重要。这些知识将有助于创新的非激素避孕疗法的发展，也将有助于为特发性不孕妇女制定治疗策略。大约15%的夫妇对孩子的渴望没有得到满足。为了优化辅助生殖治疗，迫切需要新的卵母细胞质量控制参数。我们将研究卵母细胞纳米压痕作为一种快速、无偏、无损的卵母细胞质量控制方法。

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.