Multifactorial Regulation of Ovarian Function in Fish

鱼类卵巢功能的多因素调节

• 批准号: RGPIN-2015-06277
• 负责人: VanDerKraak, Glen
• 金额: $ 3.57万
• 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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614050
• 关键词: Multifactorial; Regulation; Ovarian; Function; Fish

The long-term objective of my research is to understand the mechanisms by which pituitary gonadotropins and ovarian derived sex steroids, eicosanoids and protein growth factors regulate ovarian development in fish. My research has contributed to defining the hormones and signal transduction pathways that mediate ovarian follicle cell survival, steroidogenesis, oocyte final maturation and ovulation and integrating these responses at the whole animal level in terms of effects on spawning success. Although there have been considerable advances in the study of events controlling preovulatory ovarian development, there continues to be significant gaps in our understanding of how a follicle is selected to mature and ovulate. My research over the next 5 years will investigate the hormonal regulation of ovarian development focusing on the acquisition of follicular cell maturational and ovulatory competency using the zebrafish as the model. The research will focus on two main topics. The first of these will characterize the ontogeny of eicosanoid synthesis and action during the preovulatory period focusing on the changes that occur as the follicle progresses through the mid-vitellogenic to the full grown stage of follicular development. These studies will investigate the expression and regulation of prostaglandin and leukotriene receptors in the ovarian follicle. Subsequent studies will investigate the downstream targets of eicosanoid action and identify proteases that contribute to ovarian follicle cell rupture and ovulation of the oocyte. Based on increasing evidence that ovarian derived growth factors play an integral role in ovarian development, my second major research focus will on the insulin-like growth factor and corticotropin releasing factor families, which include ligands, receptors and binding proteins. This research involves characterizing the expression and localization of these hormone family members during the preovulatory period and also their role in ovarian development through studies involving hormone/receptor antagonists or mRNA knockdown in order to examine the effects of loss of function on biological response. The knowledge gained by this research is fundamental to understanding reproductive fitness and provides the toolbox that enables examination of the mechanisms by which endocrine disrupting compounds and other environmental factors affect ovarian physiology in fish. The planned studies are designed to position my group as a global leader in the areas of comparative endocrinology and environmental sciences.

本研究的长期目标是了解垂体促性腺激素和卵巢衍生性类固醇、类花生酸和蛋白质生长因子调节鱼类卵巢发育的机制。我的研究有助于确定调节卵泡细胞存活，类固醇生成，卵母细胞最终成熟和排卵的激素和信号转导途径，并在整个动物水平上整合这些反应对产卵成功的影响。虽然在控制排卵前卵巢发育的研究方面已经取得了相当大的进展，但在我们对卵泡如何被选择成熟和排卵的理解方面仍然存在重大差距。我在未来5年的研究将调查卵巢发育的激素调节，重点是以斑马鱼为模型获得卵泡细胞成熟和排卵能力。研究将集中在两个主要课题上。其中第一个将描述在排卵前期类花生酸合成和作用的个体发生，重点是卵泡发育过程中发生的变化，通过中期卵黄到卵泡发育的完全成熟阶段。这些研究将探讨前列腺素和白三烯受体在卵泡中的表达和调节。后续的研究将调查类花生酸作用的下游靶点，并鉴定有助于卵泡细胞破裂和卵母细胞排卵的蛋白酶。基于越来越多的证据表明卵巢衍生生长因子在卵巢发育中起着不可或缺的作用，我的第二个主要研究重点将是胰岛素样生长因子和促肾上腺皮质激素释放因子家族，包括配体，受体和结合蛋白。这项研究涉及表征这些激素家族成员在排卵前期间的表达和定位，以及它们在卵巢发育中的作用，通过涉及激素/受体拮抗剂或mRNA敲低的研究，以检查功能丧失对生物反应的影响。这项研究所获得的知识是了解生殖健康的基础，并提供了工具箱，使检查内分泌干扰化合物和其他环境因素影响鱼类卵巢生理的机制。计划中的研究旨在将我的团队定位为比较内分泌学和环境科学领域的全球领导者。