Endocrine Control of Fish Reproduction

生殖是一个复杂的过程，需要各种信号分子（如激素和生长因子）的精确控制。雌性生殖的一个关键事件是卵母细胞的生长（大小增加）和它们成熟为受精卵。我的nserc资助的研究项目的总体目标是确定垂体产生的激素如何与卵巢产生的激素和生长因子一起调节卵母细胞的发育。我们发现转化生长因子- β (tgf - β)家族的几个成员调节斑马鱼卵巢中的卵母细胞成熟。最近，我们描述了介导这些生长因子在卵巢中的作用的关键细胞途径。此外，我们已经确定了tgf - β家族的其他成员，节点相关1 （Ndr1）和Ndr2，以及一组被称为microrna的小rna，作为卵母细胞生长和成熟的潜在调节因子。在未来5年，我们将继续以斑马鱼为模型，研究激素、生长因子和microrna的综合作用如何调控卵母细胞的生长和成熟。***提出了两个具体目标：***1)Nodal信号通路的作用：***Nodal信号Ndr1和Ndr2在胚胎发育过程中起关键作用。然而，它们在成人卵巢中的功能尚不清楚。我们最近的研究结果表明，淋巴结信号可能促进卵母细胞早期生长，但抑制卵母细胞成熟。在本研究中，我们将首先增加或减少卵巢内Ndr1和Ndr2的产量，并观察这对卵母细胞生长和激素诱导的卵母细胞成熟的影响。我们还将研究介导Ndr1和Ndr2在卵巢中的作用的细胞内信号通路。***2) microrna的作用*** microrna是生理过程的重要调节因子。它们在卵母细胞生长和成熟中的作用尚不清楚。我们最近的研究表明，卵泡细胞（卵母细胞周围的细胞）产生的microrna可能对卵母细胞的生长和成熟很重要。为了验证这种可能性，我们将首先抑制参与microRNA产生的酶的编码基因的表达，并确定这些基因的缺失是否会影响卵母细胞的生长和成熟。然后，我们将测试几种microrna在调节生长因子信号和卵母细胞发育中的作用。***所提出的研究将为卵母细胞生长和成熟的调控提供新的见解。它们将增强我们对脊椎动物繁殖的全面了解。这些研究也可能对妇女的生殖健康和生育能力产生影响。最后，了解如何调节鱼类繁殖在水产养殖中具有潜在的应用价值。

Reproduction is a complex process that requires precise control by various signaling molecules, such as hormones and growth factors. A key event in female reproduction is the growth of oocytes (increase in size) and their maturation into fertilizable eggs. The overall goal of my NSERC-funded research program is to determine how hormones produced from the pituitary gland work with hormones and growth factors produced within the ovary to regulate oocyte development. We showed that several members of the transforming growth factor-beta (TGF-beta) family regulate oocyte maturation in the zebrafish ovary. More recently, we described key cellular pathways that mediate the effects of these growth factors in the ovary. In addition, we have identified additional members of the TGF-beta family, Nodal-related 1 (Ndr1) and Ndr2, and a group of small RNAs, named microRNAs, as potential regulators of oocyte growth and maturation. In the next five years, we will continue to use zebrafish as a model to study how oocyte growth and maturation are regulated by integrative functioning of hormones, growth factors and microRNAs. ***Two specific aims are proposed:***1) Roles of the Nodal signaling pathway:***Nodal signals, Ndr1 and Ndr2, play critical roles during embryonic development. However, their function in the adult ovary is not known. Our recent findings suggest that the Nodal signals may promote early oocyte growth but inhibit oocyte maturation. In this study, we will first increase or decrease the amount of Ndr1 and Ndr2 production within the ovary and observe how this affect oocyte growth and hormones-induced oocyte maturation. We will also study the intracellular signaling pathways that mediate Ndr1 and Ndr2 actions in the ovary. ***2) Roles of microRNAs***MicroRNAs are important regulators of physiological processes. Their functions in oocyte growth and maturation are poorly understood. Our recent studies suggest that microRNAs produced from follicular cells (cells that surround oocytes) may be important for oocyte growth and maturation. To test this possibility, we will first inhibit the expression of genes that encode for the enzymes involved in microRNA production and determine if oocyte growth and maturation are affected by loss of these genes. We will then test the effects of several microRNAs in modulating growth factor signaling and oocyte development.***The proposed studies will provide new insights into the regulation of oocyte growth and maturation. They will enhance our overall understanding of vertebrate reproduction. These studies may also have impacts on women's reproductive health and fertility. Finally, understanding how fish reproduction is regulated has potential applications in aquaculture.