Multifactorial regulation of ovarian function in fish

鱼类卵巢功能的多因素调控

• 批准号: RGPIN-2020-06120
• 负责人: VanDerKraak, Glen
• 金额: $ 2.4万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741054
• 关键词: Multifactorial; regulation; ovarian; function; fish

The long term goal of my research program is to understand the hormonal regulation of ovarian development in fish, focusing on the acquisition of follicular cell maturational and ovulatory competency. Using zebrafish as our model species, our research addresses fundamental questions regarding which hormones affect follicular development and if there are hallmark responses that determine whether a follicle is destined to mature and ovulate. This research is important not only to understanding the reproductive biology of fish, but also to understanding and monitoring the toxicological effects of endocrine disrupting compounds and other environmental factors in our waterways. The ovulation of a mature oocyte requires a series of coordinated events that lead to follicular somatic cell differentiation and oocyte development. The final stages of follicular recruitment leading to ovulation are dependant on luteinizing hormone (LH), sex steroids and prostaglandins (PG). The absence of these hormones leads to anovulation and follicle degeneration. However, the precise features that contribute to successful follicle development remains elusive, and are further complicated by the fact that many locally derived hormones, growth factors and other regulators are critical to these processes. Over the next 5 years we will advance our understanding the hormonal regulation of ovarian development in zebrafish by focusing on the acquisition of follicular cell maturational and ovulatory competency. First, we will investigate the timing, regulation and dependence of LH, the fish-specific progesterone derivative 17a,20ßP and its nuclear receptor, and PG in controlling the expression and activities of proteases which are required for ovulation. Second, we will investigate microRNAs (miRNAs) that are suspected of influencing the development of the ovarian follicle during the periovulatory period. These studies will include measuring the expression of selected miRNA in relation to spontaneous and hormonally induced ovulation. We will also modulate miRNA levels and determine how this affects steroid and PG biosynthesis and the induction of oocyte maturation. Lastly, we will investigate the insulin-like growth factor (IGF) family, which consists of multiple ligands, receptors and binding proteins, on the physiology of the ovarian follicle. Specifically, we will determine how the IGF3 ligand and IGF receptor antagonists affect the production of hormones (steroids and PGs) and expression of selected target genes. Collectively, these studies will address important and novel questions concerning the hormonal control of oocyte maturation and ovulation in the zebrafish that are relevant to both reproductive physiology and environmental toxicology. The planned studies will support my lab's ongoing global leadership in the areas of comparative endocrinology and environmental sciences, and provide a rich training environment for graduate and undergraduate trainees.

我的长期研究目标是了解鱼类卵巢发育的激素调节，重点是卵泡细胞成熟和排卵能力的获得。使用斑马鱼作为我们的模型物种，我们的研究解决了关于哪些激素影响卵泡发育以及是否存在决定卵泡是否注定成熟和排卵的标志性反应的基本问题。这项研究不仅对了解鱼类的生殖生物学，而且对了解和监测我们水道中内分泌干扰化合物和其他环境因素的毒理学影响具有重要意义。成熟卵母细胞的排卵需要一系列协调的事件，导致卵泡体细胞分化和卵母细胞发育。卵泡募集的最后阶段导致排卵依赖于黄体生成素（LH），性类固醇和前列腺素（PG）。这些激素的缺乏导致无排卵和卵泡变性。然而，促成卵泡成功发育的确切特征仍然难以捉摸，并且由于许多局部来源的激素、生长因子和其他调节因子对这些过程至关重要，这一事实进一步复杂化。在接下来的5年里，我们将通过专注于卵泡细胞成熟和排卵能力的获得来推进我们对斑马鱼卵巢发育激素调节的理解。首先，我们将研究LH、鱼类特异性黄体酮衍生物17a、20ßP及其核受体、PG在控制排卵所需蛋白酶的表达和活性中的时间、调控和依赖性。其次，我们将研究被怀疑在排卵期影响卵泡发育的microRNAs （miRNAs）。这些研究将包括测量与自发排卵和激素诱导排卵有关的选定miRNA的表达。我们还将调节miRNA水平，并确定其如何影响类固醇和PG生物合成以及诱导卵母细胞成熟。最后，我们将探讨由多种配体、受体和结合蛋白组成的胰岛素样生长因子（IGF）家族在卵泡生理中的作用。具体来说，我们将确定IGF3配体和IGF受体拮抗剂如何影响激素（类固醇和pg）的产生和选定靶基因的表达。总的来说，这些研究将解决有关斑马鱼卵母细胞成熟和排卵的激素控制的重要和新颖的问题，这些问题与生殖生理学和环境毒理学有关。计划中的研究将支持我的实验室在比较内分泌学和环境科学领域持续的全球领导地位，并为研究生和本科生学员提供丰富的培训环境。