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.

繁殖是一个生物过程，通过该过程 有机体自我繁殖，这是所有已知生命的基本特征。经过 了解调节生殖的因素我们可以增强 重要家畜和野生动物的育种计划。相似地， 通过干预，我们可以制定新的策略来减少人口 野生动物物种对脆弱的生态系统构成威胁并导致 作为全球监管努力的一部分，母猫和母狗的不育问题 野生动物和宠物的数量。旨在监管的策略 繁殖通常以大脑为目标，以增加或减少可用性 一种叫做促性腺激素释放激素（GnRH）的激素。促性腺激素释放激素 (GnRH) 也是 称为繁殖的主调节者，负责生产 的卵子和精子。当卵子与精子受精时，它会发育成 胚胎附着在子宫壁上并发育成 胎儿。附着过程称为植入，这是一个关键的过程 实现成功妊娠的限速步骤。 最近，我们发现 两种蛋白质 Kisspeptin (KP) 和 Kisspeptin 受体 (KISS1R) 是 在小鼠子宫中发现，似乎是成功胚胎所必需的 植入。然而，在我们可以自信地说KP和KISS1R之前 调节胚胎在子宫内的着床还需要更多的研究。给定 它们潜在的生物学功能，进行这些研究很重要 了解 KP 和 KISS1R 如何调节植入并从而调节繁殖。 为此，我们将创建一种缺乏产生 KP 和 KISS1R 在其子宫中，然后询问这对子宫的能力有何影响 胚胎植入。如果胚胎无法植入，这将是无可辩驳的 证明 KP 和 KISS1R 调节着床。如果我们做出这些观察 然后我们会问是什么调节子宫中的 KP 和 KISS1R 水平。在这里我们 将重点关注性类固醇、雌激素 (E) 和黄体酮 (P)。 E 和 P 是 由卵巢产生，对于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 KISS1R 水平。使用我们已经切除卵巢和内部器官的小鼠 E 和 P 的来源，我们将添加回 E 和 P 并确定这会产生什么影响 在KP和KISS1R的水平上。如果我们发现 KP 和 KISS1R 水平是 改变后，我们将得出结论，子宫 KP 和 KISS1R 受 E2 和 P4 调节 蛋白质。 了解 KP 和 KISS1R 水平的调节因素以及 KP 和 KISS1R 水平的调节因素 KISS1R 反过来调节，是针对 KP 和目标的第一个关键步骤 KISS1R 在子宫中以增强或抑制着床，从而 生殖。