Endocrine Control of Fish Reproduction

生殖是一个复杂的过程，需要通过各种信号分子（如激素和生长因子）进行精确控制。雌性生殖的一个关键事件是卵母细胞的生长（大小增加）和它们成熟为可受精卵。我的NSERC资助的研究项目的总体目标是确定脑垂体产生的激素如何与卵巢内产生的激素和生长因子一起调节卵母细胞发育。我们发现，几个成员的转化生长因子-β（TGF-β）家族调节卵母细胞成熟的斑马鱼卵巢。最近，我们描述了介导这些生长因子在卵巢中作用的关键细胞通路。此外，我们已经确定了TGF-β家族的其他成员，Nodal相关1（Ndr 1）和Ndr 2，以及一组小RNA，称为microRNA，作为卵母细胞生长和成熟的潜在调节因子。在接下来的五年里，我们将继续使用斑马鱼作为模型来研究卵母细胞的生长和成熟是如何通过激素，生长因子和microRNA的整合功能来调节的。 提出了两个具体目标： 1)Nodal信号通路的作用： Ndr 1和Ndr 2信号在胚胎发育过程中起着关键作用。然而，它们在成年卵巢中的功能尚不清楚。我们最近的研究结果表明，Nodal信号可能促进卵母细胞的早期生长，但抑制卵母细胞的成熟。在这项研究中，我们将首先增加或减少卵巢内Ndr 1和Ndr 2的产生量，并观察这如何影响卵母细胞的生长和卵巢诱导的卵母细胞成熟。我们还将研究介导Ndr 1和Ndr 2在卵巢中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功能知之甚少。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。为了测试这种可能性，我们将首先抑制编码参与microRNA产生的酶的基因的表达，并确定卵母细胞的生长和成熟是否受到这些基因丢失的影响。然后，我们将测试几种microRNA在调节生长因子信号传导和卵母细胞发育中的作用。 这些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生殖的整体了解。这些研究也可能对妇女的生殖健康和生育力产生影响。最后，了解鱼类繁殖是如何调节的，在水产养殖中有潜在的应用。

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.