Regulation of ovarian function by somatic hyaluronidases

尽管雌性哺乳动物出生时就有大量含有卵子的未成熟卵泡，但这些卵泡中的绝大多数永远不会排卵。相反，它们将经历细胞死亡，这一现象称为细胞凋亡，并将退化。我们实验室是第一个研究降解长多糖分子的酶(称为透明质酸酶)在卵巢卵泡发育过程中的作用的实验室。我们已经证明，这些酶能够诱导细胞死亡。我们还表明，缺乏这种酶的小鼠有更健康的卵泡和排卵更多的卵子。在目前的工作中，我们将更详细地研究这些酶是如何调节卵巢功能的。首先，我们将验证当比较正常小鼠和那些缺乏透明质酸酶的小鼠时，卵泡细胞中哪些分子发生了变化。其次，我们将生产不同大小的透明质酸酶，并研究哪一种更有效地诱导细胞死亡。然后，我们将研究女性荷尔蒙如何控制卵巢中这些酶的数量。本项目的研究结果将有助于更好地了解透明质酸酶在卵巢中的功能。这种酶的失控可能与人类或家畜不孕的原因有关。此外，本研究的结果将促进我们对卵泡发育和排卵过程的了解，试图了解透明质酸酶在卵巢功能中的抑制作用。

Although female mammals are born with a large number of immature follicles containing the eggs, the vast majority of these follicles will never reach ovulation. Instead they will undergo cell death, under a phenomenon called apoptosis, and will degenerate. Our laboratory is the first one to study the role of enzymes that degrade long polysaccharide molecules (called hyaluronidases) in this process of ovarian follicle development. We have shown that these enzymes are capable of inducing cell death. We also showed that mice lacking this enzyme have healthier follicles and ovulate higher number of eggs. In the present work we will investigate in more detail how these enzymes regulate ovarian function. First, we will verify what molecules are altered in ovarian follicle cells when comparing normal mouse with those lacking hyaluronidase. Second, we will produce hyaluronidases of different sizes and study which one is more effective to induce cell death. Then, we will investigate how feminine hormones control the amount of these enzymes in the ovary. Results obtained in our project will help to better understand the functions of hyaluronidases in the ovary. It is possible that a de-regulation of this enzyme is associated with infertility causes in humans or domestic animals. Furthermore, results herein obtained will advance our knowledge on the process of follicle development and ovulation, trying to understand the suppressive role of hyaluronidases in the ovarian function.