The kisspeptin/KISS1R signaling system: Beyond the brain

Kisspeptin/KISS1R 信号系统：超越大脑

• 批准号: RGPIN-2016-04743
• 负责人: Babwah, Andy
• 金额: $ 2.04万
• 依托单位: University of Western Ontario
• 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=615275
• 关键词: kisspeptin; KISS1R; signaling; system; Beyond

Reproduction is a biological process by which an organism propagates itself and it a fundamental feature of all known life. By understanding the factors that regulate reproduction we can enhance the breeding programs of important domestic and wildlife species. Similarly, through intervention we can develop novel strategies to reduce the population of wildlife species that pose a threat to fragile ecosystems and induce sterility among female cats and dogs as part of a global effort to regulate the population of both feral animals and pets. Strategies aimed at regulating reproduction often target the brain, to increase or decrease the availability of a hormone called the gonadotropin-releasing hormone (GnRH). GnRH is also called the master regulator of reproduction and is responsible for the production of the egg and sperm. When an egg is fertilized by a sperm it develops into an embryo which attaches itself to the wall of the uterus and develops into the fetus. The attachment process is called implantation and it is a critical rate-limiting step in achieving a successful pregnancy. Recently, we discovered that two proteins, kisspeptin (KP) and the kisspeptin receptor (KISS1R), are found in the uterus of mice and appear necessary for successful embryo implantation. However, before we can confidently say that KP and KISS1R regulate embryo implantation in the uterus more studies are required. Given their potential biological function, it is important to conduct these studies to understand how KP and KISS1R regulate implantation and thereby reproduction. To do this, we will create a mouse that lacks the ability to produce KP and KISS1R in its uterus and then ask what effect this has on the ability of the embryo to implant. If the embryo fails to implant this will be irrefutable proof that KP and KISS1R regulate implantation. If we make those observations we will then ask what regulates KP and KISS1R levels in the uterus. Here we will focus on the sex steroids, estrogen (E) and progesterone (P). E and P are made by the ovaries and are critical for embryo implantation and survival. Thus, it is possible that ovarian E and/or P regulate uterine KP and KISS1R levels. Using mice in which we have removed the ovaries and hence the internal source of E and P, we will add back E and P and determine what effect this has on the levels of KP and KISS1R. If we find that KP and KISS1R levels are altered we will conclude that uterine KP and KISS1R are E2- and P4-regulated proteins. Understanding what regulates KP and KISS1R levels and what KP and KISS1R regulate in turn, are the first critical steps towards targeting KP and KISS1R in the uterus in order to enhance or inhibit implantation and thereby reproduction.

生殖是一个生物过程， 有机体能自我繁殖，这是所有已知生命的基本特征。通过 了解调节生殖的因素，我们可以提高 重要家养和野生物种的繁殖计划。同样地， 通过干预，我们可以制定新的战略， 对脆弱的生态系统构成威胁， 雌性猫和狗的不孕症，作为全球努力调节 野生动物和宠物的数量。旨在管制的战略 生殖往往针对大脑，以增加或减少可用性 一种名为促性腺激素释放激素（GnRH）的激素。GnRH也是 被称为繁殖的主调节器，负责生产 卵子和精子当卵子与精子受精后， 胚胎附着在子宫壁上，发育成 胎儿附着过程称为植入， 成功怀孕的限速步骤。 最近，我们发现 两种蛋白质，kisspeptin（KP）和kisspeptin受体（KISS 1 R）， 在小鼠子宫中发现， 置入然而，在我们可以自信地说，KP和KISS 1 R 调节子宫内胚胎着床需要更多的研究。给定 其潜在的生物学功能，进行这些研究是重要的 了解KP和KISS 1 R如何调节着床，从而繁殖。 为了做到这一点，我们将创造一个缺乏产生KP能力的小鼠， KISS 1 R在其子宫，然后问这对能力的影响， 胚胎植入如果胚胎无法植入，这将是无可辩驳的 证明KP和KISS 1 R调节着床。如果我们观察到 然后我们将询问是什么调节子宫中的KP和KISS 1 R水平。这里我们 将集中在性类固醇，雌激素（E）和孕激素（P）。E和P是 由卵巢产生，对胚胎植入和存活至关重要。 因此，卵巢E和/或P可能调节子宫KP和KISS 1 R 程度.使用的小鼠，我们已经删除卵巢，因此内部 E和P的来源，我们将添加回E和P，并确定这有什么影响 KP和KISS 1 R的水平。如果我们发现KP和KISS 1 R水平 我们可以得出结论，子宫KP和KISS 1 R是E2和P4调节的， proteins. 了解什么调节KP和KISS 1 R水平，什么是KP和KISS 1 R水平。 KISS 1 R反过来调节，是第一个关键步骤，以针对KP和 KISS 1 R在子宫中的作用，以增强或抑制着床，从而 生殖